PexeLizumab for Acute ST-elevation myocardial infarction in patients undergoing primary percutaneous coronary intervention

A randomized controlled trial

Paul W. Armstrong, N. Bett, D. Brieger, D. Chew, R. Dick, A. Farshid, P. Garrahy, B. Gunalingham, R. Hendriks, J. Horowitz, N. Jepson, J. Lefkovits, S. Lo, I. Meredith, G. Nelson, G. New, A. Prasan, J. Rankin, P. Thompson, S. Worthley & 273 others R. Yadav, K. Huber, G. Maurer, P. Siostrzonek, J. Boland, C. Covens, W. Desmet, K. Dujardin, M. Vrolix, C. Buller, P. Klinke, C. Lazzam, S. Lutchmedial, M. Madan, M. Natarajan, F. Reeves, J. Rodes Cabau, B. Rose, E. Schampaert, P. Theroux, M. Traboulsi, J. Webb, R. Welsh, R. Zimmerman, M. Aschermann, M. Branny, T. Budesinsky, P. Cervinka, H. Frantisek, T. Frantisek, L. Groch, P. Kala, M. Ritcher, R. Rokyta, J. St'asek, R. Stipal, I. Varvarovsky, D. Zamanek, M. Zelizko, T. Toftegaard Nielsen, K. Rasmussen, P. RiisHansen, P. Thayssen, P. Beaufils, P. Geslin, Y. Gottwalles, H. Lebreton, H. LeMarec, G. Montalescot, G. Roul, P. G. Steg, C. Tronc, H. J. Berger, M. Borggrefe, J. Brachmann, P. Braun, M. Buerke, H. R. Figulla, H. Guelker, G. Hasenfuss, T. Heitzer, H. Heuer, E. Hoffman, S. Hoffmann, K. H. Kuck, F. J. Neumann, J. Neuzner, M. Rau, G. Richardt, H. Schunkert, R. Stern, W. Von Schedit, P. C. Werner, R. Zahn, G. Binetti, E. Bramucci, G. Carosio, A. Manari, A. Marzocchi, M. Medda, G. Piovaccari, A. Politi, L. Vignali, R. Violini, M. Zanchetta, R. Zanini, K. Marques, H. Otto Peels, T. Slagboom, P. C. Smits, H. Suryapranata, M. J. Suttorp, M. Van-DerEnt, I. Crozier, G. Devlin, S. Harding, H. White, G. Wilkins, M. Krzeminska-Pakula, K. Loboz-Grudzien, W. Ruźyllo, W. Tracz, M. Trusz-Gluza, M. Almeida, J. Correiada Cunha, P. Farto Abreu, L. Mourão, H. Pereira, L. Providencia, R. Vascoda Gama, A. Bertriu, C. Cuellas, E. Esplugas, E. Garcia Fernandez, X. Goicolea, J. M. Hernandez, C. Macaya, V. Mainar, A. Sanchez, P. Erikksson, S. James, G. Olivercrona, C. M. Pripp, E. Camenzind, M. Pfisterer, M. Pieper, H. Rickli, R. Acheatel, A. Ahmad, A. Albirini, R. Allen, A. Amkieh, H. V. Anderson, J. Anderson, B. Armstrong, W. Asfour, T. Ayres, M. Azrin, Z. Baber, L. Barr, G. Barsness, J. Batty, M. Bikkina, J. Blankenship, D. Campbell, P. Caples, T. Carlson, J. Chambers, H. Chandna, B. Cheek, J. Cheirif, A. Chu, H. Colfer, B. Crenshaw, S. David, A. DeFranco, J. Dehoya, J. Diez, G. Eaton, E. Eichhorn, M. El Shahawy, T. Farah, W. Felten, D. Fortuin, M. Foster, D. S. Gantt, J. Gard, M. Ghali, R. Glaser, M. Greenberg, J. Griffin, G. Hanovich, N. Hassinger, S. Heifetz, T. Henry, J. Hermiller, J. Hernandez, R. Hodson, M. Imburgia, B. Iteld, Z. Jafar, A. Jain, N. Jamal, G. Kang, R. Karlsberg, S. Khanal, S. Khoury, J. Kieval, Robert Kipperman, B. Kluck, D. Kong, E. Kosinski, M. Kozak, H. Kozman, P. Kraft, A. Labroo, P. Lai, N. Lakkis, G. Lane, B. Laretta, D. Lee, M. Leesar, J. Leggett, M. Levine, S. Lieberman, M. Lim, J. Luber, V. Marques, K. Marzo, J. McGarvey, G. McKendall, B. McLellan, M. Meengs, D. Mego, A. Mehra, J. A. Messenger, J. O. Messenger, M. Midei, M. Miller, D. Moliterno, K. Momah, M. Mowdy, A. Nahhas, J. Navas, A. Niederman, T. Nygaard, W. O'Neill, K. Patel, S. Pfau, V. Pompili, D. Purdy, B. Reddy, A. Rees, J. Reiner, A. Riba, E. Rivera, D. Roberts, A. Rosenblatt, W. Rowe, S. Rowley, D. Rubin, K. Saeian, F. Saltiel, S. Sample, B. Sanchez, I. Sarembock, J. Saucedo, T. Schreiber, R. Shah, M. Singh, J. Slater, R. Small, C. Staniloae, P. S. Sundram, L. Swenson, G. Symkoviak, K. Tam, A. Taussig, J. Thatcher, P. Tolerico, J. Trippi, S. Turk, K. Van Osdol, R. Vicari, A. Virmani, M. Warner, R. Webel, J. Wertheimer, G. Williams, J. Williams, M. Winniford, D. Wohns, D. X.M. Zhao

Research output: Contribution to journalArticle

326 Citations (Scopus)

Abstract

Context: Reperfusion with percutaneous transluminal coronary intervention (PCI) is effective at improving outcomes in patients with acute ST-elevation myocardial infarction (STEMI). However, in patients without prompt reestablishment of brisk coronary flow and tissue perfusion, mortality remains high, providing an opportunity for novel treatments, including anti-inflammatory agents. Objective: To evaluate the effectiveness of pexelizumab, a humanized monoclonal antibody that binds the C5 component of complement, as an adjunct to PCI in improving 30-day mortality from STEMI. Design, Setting, and Patients: This trial was a prospective, multicenter, double-blind, placebo-controlled, phase 3 study of the intravenous administration of pexelizumab in conjunction with primary PCI in STEMI with prespecified high-risk electrocardiographic findings. The trial was intended to enroll 8500 patients, but in conjunction with the US Food and Drug Administration enrollment was modified to 5745 patients presenting from 296 hospitals in 17 countries from July 13, 2004, to May 11, 2006. Interventions: Two thousand eight hundred eighty-five patients were randomly assigned to receive placebo and 2860 to receive pexelizumab given as a 2-mg/kg intravenous bolus prior to PCI followed by 0.05-mg/kg per hour infusion over the subsequent 24 hours. Patients were randomized within 6 hours of symptom onset. Main Outcome Measures: The primary end point was all-cause mortality through day 30. Secondary end points were death through day 90 and the composite of death, cardiogenic shock, or congestive heart failure through days 30 and 90. Results: No difference in mortality through day 30 was observed between the pexelizumab and placebo treatment groups, with 116 patients (4.06%) and 113 patients (3.92%) who died in the respective groups (hazard ratio [HR], 1.04; 95% confidence interval [CI], 0.80-1.35; log-rank P=.78). The composite end points of death, shock, or heart failure were also similar with 257 patients (8.99%) receiving pexelizumab and 265 patients (9.19%) receiving placebo at 30 days (HR, 0.98; 95% CI, 0.83-1.16; P=.81) and 293 patients (10.24%) receiving pexelizumab and 293 patients (10.16%) receiving placebo at 90 days (HR, 1.01; 95% CI, 0.86-1.19; P=.91). Conclusion: In this large clinical trial of patients treated with primary PCI for STEMI, mortality was low and unaffected by administration of pexelizumab.

Original languageEnglish (US)
Pages (from-to)43-51
Number of pages9
JournalJournal of the American Medical Association
Volume297
Issue number1
DOIs
StatePublished - Jan 3 2007

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Percutaneous Coronary Intervention
Randomized Controlled Trials
Placebos
Mortality
Confidence Intervals
pexelizumab
ST Elevation Myocardial Infarction
Heart Failure
Complement C5
Antibodies, Monoclonal, Humanized
Cardiogenic Shock
United States Food and Drug Administration
Intravenous Administration
Reperfusion
Shock
Anti-Inflammatory Agents
Perfusion

All Science Journal Classification (ASJC) codes

  • Medicine(all)

Cite this

Armstrong, Paul W. ; Bett, N. ; Brieger, D. ; Chew, D. ; Dick, R. ; Farshid, A. ; Garrahy, P. ; Gunalingham, B. ; Hendriks, R. ; Horowitz, J. ; Jepson, N. ; Lefkovits, J. ; Lo, S. ; Meredith, I. ; Nelson, G. ; New, G. ; Prasan, A. ; Rankin, J. ; Thompson, P. ; Worthley, S. ; Yadav, R. ; Huber, K. ; Maurer, G. ; Siostrzonek, P. ; Boland, J. ; Covens, C. ; Desmet, W. ; Dujardin, K. ; Vrolix, M. ; Buller, C. ; Klinke, P. ; Lazzam, C. ; Lutchmedial, S. ; Madan, M. ; Natarajan, M. ; Reeves, F. ; Rodes Cabau, J. ; Rose, B. ; Schampaert, E. ; Theroux, P. ; Traboulsi, M. ; Webb, J. ; Welsh, R. ; Zimmerman, R. ; Aschermann, M. ; Branny, M. ; Budesinsky, T. ; Cervinka, P. ; Frantisek, H. ; Frantisek, T. ; Groch, L. ; Kala, P. ; Ritcher, M. ; Rokyta, R. ; St'asek, J. ; Stipal, R. ; Varvarovsky, I. ; Zamanek, D. ; Zelizko, M. ; Toftegaard Nielsen, T. ; Rasmussen, K. ; RiisHansen, P. ; Thayssen, P. ; Beaufils, P. ; Geslin, P. ; Gottwalles, Y. ; Lebreton, H. ; LeMarec, H. ; Montalescot, G. ; Roul, G. ; Steg, P. G. ; Tronc, C. ; Berger, H. J. ; Borggrefe, M. ; Brachmann, J. ; Braun, P. ; Buerke, M. ; Figulla, H. R. ; Guelker, H. ; Hasenfuss, G. ; Heitzer, T. ; Heuer, H. ; Hoffman, E. ; Hoffmann, S. ; Kuck, K. H. ; Neumann, F. J. ; Neuzner, J. ; Rau, M. ; Richardt, G. ; Schunkert, H. ; Stern, R. ; Von Schedit, W. ; Werner, P. C. ; Zahn, R. ; Binetti, G. ; Bramucci, E. ; Carosio, G. ; Manari, A. ; Marzocchi, A. ; Medda, M. ; Piovaccari, G. ; Politi, A. ; Vignali, L. ; Violini, R. ; Zanchetta, M. ; Zanini, R. ; Marques, K. ; Otto Peels, H. ; Slagboom, T. ; Smits, P. C. ; Suryapranata, H. ; Suttorp, M. J. ; Van-DerEnt, M. ; Crozier, I. ; Devlin, G. ; Harding, S. ; White, H. ; Wilkins, G. ; Krzeminska-Pakula, M. ; Loboz-Grudzien, K. ; Ruźyllo, W. ; Tracz, W. ; Trusz-Gluza, M. ; Almeida, M. ; Correiada Cunha, J. ; Farto Abreu, P. ; Mourão, L. ; Pereira, H. ; Providencia, L. ; Vascoda Gama, R. ; Bertriu, A. ; Cuellas, C. ; Esplugas, E. ; Garcia Fernandez, E. ; Goicolea, X. ; Hernandez, J. M. ; Macaya, C. ; Mainar, V. ; Sanchez, A. ; Erikksson, P. ; James, S. ; Olivercrona, G. ; Pripp, C. M. ; Camenzind, E. ; Pfisterer, M. ; Pieper, M. ; Rickli, H. ; Acheatel, R. ; Ahmad, A. ; Albirini, A. ; Allen, R. ; Amkieh, A. ; Anderson, H. V. ; Anderson, J. ; Armstrong, B. ; Asfour, W. ; Ayres, T. ; Azrin, M. ; Baber, Z. ; Barr, L. ; Barsness, G. ; Batty, J. ; Bikkina, M. ; Blankenship, J. ; Campbell, D. ; Caples, P. ; Carlson, T. ; Chambers, J. ; Chandna, H. ; Cheek, B. ; Cheirif, J. ; Chu, A. ; Colfer, H. ; Crenshaw, B. ; David, S. ; DeFranco, A. ; Dehoya, J. ; Diez, J. ; Eaton, G. ; Eichhorn, E. ; El Shahawy, M. ; Farah, T. ; Felten, W. ; Fortuin, D. ; Foster, M. ; Gantt, D. S. ; Gard, J. ; Ghali, M. ; Glaser, R. ; Greenberg, M. ; Griffin, J. ; Hanovich, G. ; Hassinger, N. ; Heifetz, S. ; Henry, T. ; Hermiller, J. ; Hernandez, J. ; Hodson, R. ; Imburgia, M. ; Iteld, B. ; Jafar, Z. ; Jain, A. ; Jamal, N. ; Kang, G. ; Karlsberg, R. ; Khanal, S. ; Khoury, S. ; Kieval, J. ; Kipperman, Robert ; Kluck, B. ; Kong, D. ; Kosinski, E. ; Kozak, M. ; Kozman, H. ; Kraft, P. ; Labroo, A. ; Lai, P. ; Lakkis, N. ; Lane, G. ; Laretta, B. ; Lee, D. ; Leesar, M. ; Leggett, J. ; Levine, M. ; Lieberman, S. ; Lim, M. ; Luber, J. ; Marques, V. ; Marzo, K. ; McGarvey, J. ; McKendall, G. ; McLellan, B. ; Meengs, M. ; Mego, D. ; Mehra, A. ; Messenger, J. A. ; Messenger, J. O. ; Midei, M. ; Miller, M. ; Moliterno, D. ; Momah, K. ; Mowdy, M. ; Nahhas, A. ; Navas, J. ; Niederman, A. ; Nygaard, T. ; O'Neill, W. ; Patel, K. ; Pfau, S. ; Pompili, V. ; Purdy, D. ; Reddy, B. ; Rees, A. ; Reiner, J. ; Riba, A. ; Rivera, E. ; Roberts, D. ; Rosenblatt, A. ; Rowe, W. ; Rowley, S. ; Rubin, D. ; Saeian, K. ; Saltiel, F. ; Sample, S. ; Sanchez, B. ; Sarembock, I. ; Saucedo, J. ; Schreiber, T. ; Shah, R. ; Singh, M. ; Slater, J. ; Small, R. ; Staniloae, C. ; Sundram, P. S. ; Swenson, L. ; Symkoviak, G. ; Tam, K. ; Taussig, A. ; Thatcher, J. ; Tolerico, P. ; Trippi, J. ; Turk, S. ; Van Osdol, K. ; Vicari, R. ; Virmani, A. ; Warner, M. ; Webel, R. ; Wertheimer, J. ; Williams, G. ; Williams, J. ; Winniford, M. ; Wohns, D. ; Zhao, D. X.M. / PexeLizumab for Acute ST-elevation myocardial infarction in patients undergoing primary percutaneous coronary intervention : A randomized controlled trial. In: Journal of the American Medical Association. 2007 ; Vol. 297, No. 1. pp. 43-51.
@article{0a11229563154840a5681d89d7e54f1b,
title = "PexeLizumab for Acute ST-elevation myocardial infarction in patients undergoing primary percutaneous coronary intervention: A randomized controlled trial",
abstract = "Context: Reperfusion with percutaneous transluminal coronary intervention (PCI) is effective at improving outcomes in patients with acute ST-elevation myocardial infarction (STEMI). However, in patients without prompt reestablishment of brisk coronary flow and tissue perfusion, mortality remains high, providing an opportunity for novel treatments, including anti-inflammatory agents. Objective: To evaluate the effectiveness of pexelizumab, a humanized monoclonal antibody that binds the C5 component of complement, as an adjunct to PCI in improving 30-day mortality from STEMI. Design, Setting, and Patients: This trial was a prospective, multicenter, double-blind, placebo-controlled, phase 3 study of the intravenous administration of pexelizumab in conjunction with primary PCI in STEMI with prespecified high-risk electrocardiographic findings. The trial was intended to enroll 8500 patients, but in conjunction with the US Food and Drug Administration enrollment was modified to 5745 patients presenting from 296 hospitals in 17 countries from July 13, 2004, to May 11, 2006. Interventions: Two thousand eight hundred eighty-five patients were randomly assigned to receive placebo and 2860 to receive pexelizumab given as a 2-mg/kg intravenous bolus prior to PCI followed by 0.05-mg/kg per hour infusion over the subsequent 24 hours. Patients were randomized within 6 hours of symptom onset. Main Outcome Measures: The primary end point was all-cause mortality through day 30. Secondary end points were death through day 90 and the composite of death, cardiogenic shock, or congestive heart failure through days 30 and 90. Results: No difference in mortality through day 30 was observed between the pexelizumab and placebo treatment groups, with 116 patients (4.06{\%}) and 113 patients (3.92{\%}) who died in the respective groups (hazard ratio [HR], 1.04; 95{\%} confidence interval [CI], 0.80-1.35; log-rank P=.78). The composite end points of death, shock, or heart failure were also similar with 257 patients (8.99{\%}) receiving pexelizumab and 265 patients (9.19{\%}) receiving placebo at 30 days (HR, 0.98; 95{\%} CI, 0.83-1.16; P=.81) and 293 patients (10.24{\%}) receiving pexelizumab and 293 patients (10.16{\%}) receiving placebo at 90 days (HR, 1.01; 95{\%} CI, 0.86-1.19; P=.91). Conclusion: In this large clinical trial of patients treated with primary PCI for STEMI, mortality was low and unaffected by administration of pexelizumab.",
author = "Armstrong, {Paul W.} and N. Bett and D. Brieger and D. Chew and R. Dick and A. Farshid and P. Garrahy and B. Gunalingham and R. Hendriks and J. Horowitz and N. Jepson and J. Lefkovits and S. Lo and I. Meredith and G. Nelson and G. New and A. Prasan and J. Rankin and P. Thompson and S. Worthley and R. Yadav and K. Huber and G. Maurer and P. Siostrzonek and J. Boland and C. Covens and W. Desmet and K. Dujardin and M. Vrolix and C. Buller and P. Klinke and C. Lazzam and S. Lutchmedial and M. Madan and M. Natarajan and F. Reeves and {Rodes Cabau}, J. and B. Rose and E. Schampaert and P. Theroux and M. Traboulsi and J. Webb and R. Welsh and R. Zimmerman and M. Aschermann and M. Branny and T. Budesinsky and P. Cervinka and H. Frantisek and T. Frantisek and L. Groch and P. Kala and M. Ritcher and R. Rokyta and J. St'asek and R. Stipal and I. Varvarovsky and D. Zamanek and M. Zelizko and {Toftegaard Nielsen}, T. and K. Rasmussen and P. RiisHansen and P. Thayssen and P. Beaufils and P. Geslin and Y. Gottwalles and H. Lebreton and H. LeMarec and G. Montalescot and G. Roul and Steg, {P. G.} and C. Tronc and Berger, {H. J.} and M. Borggrefe and J. Brachmann and P. Braun and M. Buerke and Figulla, {H. R.} and H. Guelker and G. Hasenfuss and T. Heitzer and H. Heuer and E. Hoffman and S. Hoffmann and Kuck, {K. H.} and Neumann, {F. J.} and J. Neuzner and M. Rau and G. Richardt and H. Schunkert and R. Stern and {Von Schedit}, W. and Werner, {P. C.} and R. Zahn and G. Binetti and E. Bramucci and G. Carosio and A. Manari and A. Marzocchi and M. Medda and G. Piovaccari and A. Politi and L. Vignali and R. Violini and M. Zanchetta and R. Zanini and K. Marques and {Otto Peels}, H. and T. Slagboom and Smits, {P. C.} and H. Suryapranata and Suttorp, {M. J.} and M. Van-DerEnt and I. Crozier and G. Devlin and S. Harding and H. White and G. Wilkins and M. Krzeminska-Pakula and K. Loboz-Grudzien and W. Ruźyllo and W. Tracz and M. Trusz-Gluza and M. Almeida and {Correiada Cunha}, J. and {Farto Abreu}, P. and L. Mour{\~a}o and H. Pereira and L. Providencia and {Vascoda Gama}, R. and A. Bertriu and C. Cuellas and E. Esplugas and {Garcia Fernandez}, E. and X. Goicolea and Hernandez, {J. M.} and C. Macaya and V. Mainar and A. Sanchez and P. Erikksson and S. James and G. Olivercrona and Pripp, {C. M.} and E. Camenzind and M. Pfisterer and M. Pieper and H. Rickli and R. Acheatel and A. Ahmad and A. Albirini and R. Allen and A. Amkieh and Anderson, {H. V.} and J. Anderson and B. Armstrong and W. Asfour and T. Ayres and M. Azrin and Z. Baber and L. Barr and G. Barsness and J. Batty and M. Bikkina and J. Blankenship and D. Campbell and P. Caples and T. Carlson and J. Chambers and H. Chandna and B. Cheek and J. Cheirif and A. Chu and H. Colfer and B. Crenshaw and S. David and A. DeFranco and J. Dehoya and J. Diez and G. Eaton and E. Eichhorn and {El Shahawy}, M. and T. Farah and W. Felten and D. Fortuin and M. Foster and Gantt, {D. S.} and J. Gard and M. Ghali and R. Glaser and M. Greenberg and J. Griffin and G. Hanovich and N. Hassinger and S. Heifetz and T. Henry and J. Hermiller and J. Hernandez and R. Hodson and M. Imburgia and B. Iteld and Z. Jafar and A. Jain and N. Jamal and G. Kang and R. Karlsberg and S. Khanal and S. Khoury and J. Kieval and Robert Kipperman and B. Kluck and D. Kong and E. Kosinski and M. Kozak and H. Kozman and P. Kraft and A. Labroo and P. Lai and N. Lakkis and G. Lane and B. Laretta and D. Lee and M. Leesar and J. Leggett and M. Levine and S. Lieberman and M. Lim and J. Luber and V. Marques and K. Marzo and J. McGarvey and G. McKendall and B. McLellan and M. Meengs and D. Mego and A. Mehra and Messenger, {J. A.} and Messenger, {J. O.} and M. Midei and M. Miller and D. Moliterno and K. Momah and M. Mowdy and A. Nahhas and J. Navas and A. Niederman and T. Nygaard and W. O'Neill and K. Patel and S. Pfau and V. Pompili and D. Purdy and B. Reddy and A. Rees and J. Reiner and A. Riba and E. Rivera and D. Roberts and A. Rosenblatt and W. Rowe and S. Rowley and D. Rubin and K. Saeian and F. Saltiel and S. Sample and B. Sanchez and I. Sarembock and J. Saucedo and T. Schreiber and R. Shah and M. Singh and J. Slater and R. Small and C. Staniloae and Sundram, {P. S.} and L. Swenson and G. Symkoviak and K. Tam and A. Taussig and J. Thatcher and P. Tolerico and J. Trippi and S. Turk and {Van Osdol}, K. and R. Vicari and A. Virmani and M. Warner and R. Webel and J. Wertheimer and G. Williams and J. Williams and M. Winniford and D. Wohns and Zhao, {D. X.M.}",
year = "2007",
month = "1",
day = "3",
doi = "10.1001/jama.297.1.43",
language = "English (US)",
volume = "297",
pages = "43--51",
journal = "JAMA - Journal of the American Medical Association",
issn = "0002-9955",
publisher = "American Medical Association",
number = "1",

}

Armstrong, PW, Bett, N, Brieger, D, Chew, D, Dick, R, Farshid, A, Garrahy, P, Gunalingham, B, Hendriks, R, Horowitz, J, Jepson, N, Lefkovits, J, Lo, S, Meredith, I, Nelson, G, New, G, Prasan, A, Rankin, J, Thompson, P, Worthley, S, Yadav, R, Huber, K, Maurer, G, Siostrzonek, P, Boland, J, Covens, C, Desmet, W, Dujardin, K, Vrolix, M, Buller, C, Klinke, P, Lazzam, C, Lutchmedial, S, Madan, M, Natarajan, M, Reeves, F, Rodes Cabau, J, Rose, B, Schampaert, E, Theroux, P, Traboulsi, M, Webb, J, Welsh, R, Zimmerman, R, Aschermann, M, Branny, M, Budesinsky, T, Cervinka, P, Frantisek, H, Frantisek, T, Groch, L, Kala, P, Ritcher, M, Rokyta, R, St'asek, J, Stipal, R, Varvarovsky, I, Zamanek, D, Zelizko, M, Toftegaard Nielsen, T, Rasmussen, K, RiisHansen, P, Thayssen, P, Beaufils, P, Geslin, P, Gottwalles, Y, Lebreton, H, LeMarec, H, Montalescot, G, Roul, G, Steg, PG, Tronc, C, Berger, HJ, Borggrefe, M, Brachmann, J, Braun, P, Buerke, M, Figulla, HR, Guelker, H, Hasenfuss, G, Heitzer, T, Heuer, H, Hoffman, E, Hoffmann, S, Kuck, KH, Neumann, FJ, Neuzner, J, Rau, M, Richardt, G, Schunkert, H, Stern, R, Von Schedit, W, Werner, PC, Zahn, R, Binetti, G, Bramucci, E, Carosio, G, Manari, A, Marzocchi, A, Medda, M, Piovaccari, G, Politi, A, Vignali, L, Violini, R, Zanchetta, M, Zanini, R, Marques, K, Otto Peels, H, Slagboom, T, Smits, PC, Suryapranata, H, Suttorp, MJ, Van-DerEnt, M, Crozier, I, Devlin, G, Harding, S, White, H, Wilkins, G, Krzeminska-Pakula, M, Loboz-Grudzien, K, Ruźyllo, W, Tracz, W, Trusz-Gluza, M, Almeida, M, Correiada Cunha, J, Farto Abreu, P, Mourão, L, Pereira, H, Providencia, L, Vascoda Gama, R, Bertriu, A, Cuellas, C, Esplugas, E, Garcia Fernandez, E, Goicolea, X, Hernandez, JM, Macaya, C, Mainar, V, Sanchez, A, Erikksson, P, James, S, Olivercrona, G, Pripp, CM, Camenzind, E, Pfisterer, M, Pieper, M, Rickli, H, Acheatel, R, Ahmad, A, Albirini, A, Allen, R, Amkieh, A, Anderson, HV, Anderson, J, Armstrong, B, Asfour, W, Ayres, T, Azrin, M, Baber, Z, Barr, L, Barsness, G, Batty, J, Bikkina, M, Blankenship, J, Campbell, D, Caples, P, Carlson, T, Chambers, J, Chandna, H, Cheek, B, Cheirif, J, Chu, A, Colfer, H, Crenshaw, B, David, S, DeFranco, A, Dehoya, J, Diez, J, Eaton, G, Eichhorn, E, El Shahawy, M, Farah, T, Felten, W, Fortuin, D, Foster, M, Gantt, DS, Gard, J, Ghali, M, Glaser, R, Greenberg, M, Griffin, J, Hanovich, G, Hassinger, N, Heifetz, S, Henry, T, Hermiller, J, Hernandez, J, Hodson, R, Imburgia, M, Iteld, B, Jafar, Z, Jain, A, Jamal, N, Kang, G, Karlsberg, R, Khanal, S, Khoury, S, Kieval, J, Kipperman, R, Kluck, B, Kong, D, Kosinski, E, Kozak, M, Kozman, H, Kraft, P, Labroo, A, Lai, P, Lakkis, N, Lane, G, Laretta, B, Lee, D, Leesar, M, Leggett, J, Levine, M, Lieberman, S, Lim, M, Luber, J, Marques, V, Marzo, K, McGarvey, J, McKendall, G, McLellan, B, Meengs, M, Mego, D, Mehra, A, Messenger, JA, Messenger, JO, Midei, M, Miller, M, Moliterno, D, Momah, K, Mowdy, M, Nahhas, A, Navas, J, Niederman, A, Nygaard, T, O'Neill, W, Patel, K, Pfau, S, Pompili, V, Purdy, D, Reddy, B, Rees, A, Reiner, J, Riba, A, Rivera, E, Roberts, D, Rosenblatt, A, Rowe, W, Rowley, S, Rubin, D, Saeian, K, Saltiel, F, Sample, S, Sanchez, B, Sarembock, I, Saucedo, J, Schreiber, T, Shah, R, Singh, M, Slater, J, Small, R, Staniloae, C, Sundram, PS, Swenson, L, Symkoviak, G, Tam, K, Taussig, A, Thatcher, J, Tolerico, P, Trippi, J, Turk, S, Van Osdol, K, Vicari, R, Virmani, A, Warner, M, Webel, R, Wertheimer, J, Williams, G, Williams, J, Winniford, M, Wohns, D & Zhao, DXM 2007, 'PexeLizumab for Acute ST-elevation myocardial infarction in patients undergoing primary percutaneous coronary intervention: A randomized controlled trial', Journal of the American Medical Association, vol. 297, no. 1, pp. 43-51. https://doi.org/10.1001/jama.297.1.43

PexeLizumab for Acute ST-elevation myocardial infarction in patients undergoing primary percutaneous coronary intervention : A randomized controlled trial. / Armstrong, Paul W.; Bett, N.; Brieger, D.; Chew, D.; Dick, R.; Farshid, A.; Garrahy, P.; Gunalingham, B.; Hendriks, R.; Horowitz, J.; Jepson, N.; Lefkovits, J.; Lo, S.; Meredith, I.; Nelson, G.; New, G.; Prasan, A.; Rankin, J.; Thompson, P.; Worthley, S.; Yadav, R.; Huber, K.; Maurer, G.; Siostrzonek, P.; Boland, J.; Covens, C.; Desmet, W.; Dujardin, K.; Vrolix, M.; Buller, C.; Klinke, P.; Lazzam, C.; Lutchmedial, S.; Madan, M.; Natarajan, M.; Reeves, F.; Rodes Cabau, J.; Rose, B.; Schampaert, E.; Theroux, P.; Traboulsi, M.; Webb, J.; Welsh, R.; Zimmerman, R.; Aschermann, M.; Branny, M.; Budesinsky, T.; Cervinka, P.; Frantisek, H.; Frantisek, T.; Groch, L.; Kala, P.; Ritcher, M.; Rokyta, R.; St'asek, J.; Stipal, R.; Varvarovsky, I.; Zamanek, D.; Zelizko, M.; Toftegaard Nielsen, T.; Rasmussen, K.; RiisHansen, P.; Thayssen, P.; Beaufils, P.; Geslin, P.; Gottwalles, Y.; Lebreton, H.; LeMarec, H.; Montalescot, G.; Roul, G.; Steg, P. G.; Tronc, C.; Berger, H. J.; Borggrefe, M.; Brachmann, J.; Braun, P.; Buerke, M.; Figulla, H. R.; Guelker, H.; Hasenfuss, G.; Heitzer, T.; Heuer, H.; Hoffman, E.; Hoffmann, S.; Kuck, K. H.; Neumann, F. J.; Neuzner, J.; Rau, M.; Richardt, G.; Schunkert, H.; Stern, R.; Von Schedit, W.; Werner, P. C.; Zahn, R.; Binetti, G.; Bramucci, E.; Carosio, G.; Manari, A.; Marzocchi, A.; Medda, M.; Piovaccari, G.; Politi, A.; Vignali, L.; Violini, R.; Zanchetta, M.; Zanini, R.; Marques, K.; Otto Peels, H.; Slagboom, T.; Smits, P. C.; Suryapranata, H.; Suttorp, M. J.; Van-DerEnt, M.; Crozier, I.; Devlin, G.; Harding, S.; White, H.; Wilkins, G.; Krzeminska-Pakula, M.; Loboz-Grudzien, K.; Ruźyllo, W.; Tracz, W.; Trusz-Gluza, M.; Almeida, M.; Correiada Cunha, J.; Farto Abreu, P.; Mourão, L.; Pereira, H.; Providencia, L.; Vascoda Gama, R.; Bertriu, A.; Cuellas, C.; Esplugas, E.; Garcia Fernandez, E.; Goicolea, X.; Hernandez, J. M.; Macaya, C.; Mainar, V.; Sanchez, A.; Erikksson, P.; James, S.; Olivercrona, G.; Pripp, C. M.; Camenzind, E.; Pfisterer, M.; Pieper, M.; Rickli, H.; Acheatel, R.; Ahmad, A.; Albirini, A.; Allen, R.; Amkieh, A.; Anderson, H. V.; Anderson, J.; Armstrong, B.; Asfour, W.; Ayres, T.; Azrin, M.; Baber, Z.; Barr, L.; Barsness, G.; Batty, J.; Bikkina, M.; Blankenship, J.; Campbell, D.; Caples, P.; Carlson, T.; Chambers, J.; Chandna, H.; Cheek, B.; Cheirif, J.; Chu, A.; Colfer, H.; Crenshaw, B.; David, S.; DeFranco, A.; Dehoya, J.; Diez, J.; Eaton, G.; Eichhorn, E.; El Shahawy, M.; Farah, T.; Felten, W.; Fortuin, D.; Foster, M.; Gantt, D. S.; Gard, J.; Ghali, M.; Glaser, R.; Greenberg, M.; Griffin, J.; Hanovich, G.; Hassinger, N.; Heifetz, S.; Henry, T.; Hermiller, J.; Hernandez, J.; Hodson, R.; Imburgia, M.; Iteld, B.; Jafar, Z.; Jain, A.; Jamal, N.; Kang, G.; Karlsberg, R.; Khanal, S.; Khoury, S.; Kieval, J.; Kipperman, Robert; Kluck, B.; Kong, D.; Kosinski, E.; Kozak, M.; Kozman, H.; Kraft, P.; Labroo, A.; Lai, P.; Lakkis, N.; Lane, G.; Laretta, B.; Lee, D.; Leesar, M.; Leggett, J.; Levine, M.; Lieberman, S.; Lim, M.; Luber, J.; Marques, V.; Marzo, K.; McGarvey, J.; McKendall, G.; McLellan, B.; Meengs, M.; Mego, D.; Mehra, A.; Messenger, J. A.; Messenger, J. O.; Midei, M.; Miller, M.; Moliterno, D.; Momah, K.; Mowdy, M.; Nahhas, A.; Navas, J.; Niederman, A.; Nygaard, T.; O'Neill, W.; Patel, K.; Pfau, S.; Pompili, V.; Purdy, D.; Reddy, B.; Rees, A.; Reiner, J.; Riba, A.; Rivera, E.; Roberts, D.; Rosenblatt, A.; Rowe, W.; Rowley, S.; Rubin, D.; Saeian, K.; Saltiel, F.; Sample, S.; Sanchez, B.; Sarembock, I.; Saucedo, J.; Schreiber, T.; Shah, R.; Singh, M.; Slater, J.; Small, R.; Staniloae, C.; Sundram, P. S.; Swenson, L.; Symkoviak, G.; Tam, K.; Taussig, A.; Thatcher, J.; Tolerico, P.; Trippi, J.; Turk, S.; Van Osdol, K.; Vicari, R.; Virmani, A.; Warner, M.; Webel, R.; Wertheimer, J.; Williams, G.; Williams, J.; Winniford, M.; Wohns, D.; Zhao, D. X.M.

In: Journal of the American Medical Association, Vol. 297, No. 1, 03.01.2007, p. 43-51.

Research output: Contribution to journalArticle

TY - JOUR

T1 - PexeLizumab for Acute ST-elevation myocardial infarction in patients undergoing primary percutaneous coronary intervention

T2 - A randomized controlled trial

AU - Armstrong, Paul W.

AU - Bett, N.

AU - Brieger, D.

AU - Chew, D.

AU - Dick, R.

AU - Farshid, A.

AU - Garrahy, P.

AU - Gunalingham, B.

AU - Hendriks, R.

AU - Horowitz, J.

AU - Jepson, N.

AU - Lefkovits, J.

AU - Lo, S.

AU - Meredith, I.

AU - Nelson, G.

AU - New, G.

AU - Prasan, A.

AU - Rankin, J.

AU - Thompson, P.

AU - Worthley, S.

AU - Yadav, R.

AU - Huber, K.

AU - Maurer, G.

AU - Siostrzonek, P.

AU - Boland, J.

AU - Covens, C.

AU - Desmet, W.

AU - Dujardin, K.

AU - Vrolix, M.

AU - Buller, C.

AU - Klinke, P.

AU - Lazzam, C.

AU - Lutchmedial, S.

AU - Madan, M.

AU - Natarajan, M.

AU - Reeves, F.

AU - Rodes Cabau, J.

AU - Rose, B.

AU - Schampaert, E.

AU - Theroux, P.

AU - Traboulsi, M.

AU - Webb, J.

AU - Welsh, R.

AU - Zimmerman, R.

AU - Aschermann, M.

AU - Branny, M.

AU - Budesinsky, T.

AU - Cervinka, P.

AU - Frantisek, H.

AU - Frantisek, T.

AU - Groch, L.

AU - Kala, P.

AU - Ritcher, M.

AU - Rokyta, R.

AU - St'asek, J.

AU - Stipal, R.

AU - Varvarovsky, I.

AU - Zamanek, D.

AU - Zelizko, M.

AU - Toftegaard Nielsen, T.

AU - Rasmussen, K.

AU - RiisHansen, P.

AU - Thayssen, P.

AU - Beaufils, P.

AU - Geslin, P.

AU - Gottwalles, Y.

AU - Lebreton, H.

AU - LeMarec, H.

AU - Montalescot, G.

AU - Roul, G.

AU - Steg, P. G.

AU - Tronc, C.

AU - Berger, H. J.

AU - Borggrefe, M.

AU - Brachmann, J.

AU - Braun, P.

AU - Buerke, M.

AU - Figulla, H. R.

AU - Guelker, H.

AU - Hasenfuss, G.

AU - Heitzer, T.

AU - Heuer, H.

AU - Hoffman, E.

AU - Hoffmann, S.

AU - Kuck, K. H.

AU - Neumann, F. J.

AU - Neuzner, J.

AU - Rau, M.

AU - Richardt, G.

AU - Schunkert, H.

AU - Stern, R.

AU - Von Schedit, W.

AU - Werner, P. C.

AU - Zahn, R.

AU - Binetti, G.

AU - Bramucci, E.

AU - Carosio, G.

AU - Manari, A.

AU - Marzocchi, A.

AU - Medda, M.

AU - Piovaccari, G.

AU - Politi, A.

AU - Vignali, L.

AU - Violini, R.

AU - Zanchetta, M.

AU - Zanini, R.

AU - Marques, K.

AU - Otto Peels, H.

AU - Slagboom, T.

AU - Smits, P. C.

AU - Suryapranata, H.

AU - Suttorp, M. J.

AU - Van-DerEnt, M.

AU - Crozier, I.

AU - Devlin, G.

AU - Harding, S.

AU - White, H.

AU - Wilkins, G.

AU - Krzeminska-Pakula, M.

AU - Loboz-Grudzien, K.

AU - Ruźyllo, W.

AU - Tracz, W.

AU - Trusz-Gluza, M.

AU - Almeida, M.

AU - Correiada Cunha, J.

AU - Farto Abreu, P.

AU - Mourão, L.

AU - Pereira, H.

AU - Providencia, L.

AU - Vascoda Gama, R.

AU - Bertriu, A.

AU - Cuellas, C.

AU - Esplugas, E.

AU - Garcia Fernandez, E.

AU - Goicolea, X.

AU - Hernandez, J. M.

AU - Macaya, C.

AU - Mainar, V.

AU - Sanchez, A.

AU - Erikksson, P.

AU - James, S.

AU - Olivercrona, G.

AU - Pripp, C. M.

AU - Camenzind, E.

AU - Pfisterer, M.

AU - Pieper, M.

AU - Rickli, H.

AU - Acheatel, R.

AU - Ahmad, A.

AU - Albirini, A.

AU - Allen, R.

AU - Amkieh, A.

AU - Anderson, H. V.

AU - Anderson, J.

AU - Armstrong, B.

AU - Asfour, W.

AU - Ayres, T.

AU - Azrin, M.

AU - Baber, Z.

AU - Barr, L.

AU - Barsness, G.

AU - Batty, J.

AU - Bikkina, M.

AU - Blankenship, J.

AU - Campbell, D.

AU - Caples, P.

AU - Carlson, T.

AU - Chambers, J.

AU - Chandna, H.

AU - Cheek, B.

AU - Cheirif, J.

AU - Chu, A.

AU - Colfer, H.

AU - Crenshaw, B.

AU - David, S.

AU - DeFranco, A.

AU - Dehoya, J.

AU - Diez, J.

AU - Eaton, G.

AU - Eichhorn, E.

AU - El Shahawy, M.

AU - Farah, T.

AU - Felten, W.

AU - Fortuin, D.

AU - Foster, M.

AU - Gantt, D. S.

AU - Gard, J.

AU - Ghali, M.

AU - Glaser, R.

AU - Greenberg, M.

AU - Griffin, J.

AU - Hanovich, G.

AU - Hassinger, N.

AU - Heifetz, S.

AU - Henry, T.

AU - Hermiller, J.

AU - Hernandez, J.

AU - Hodson, R.

AU - Imburgia, M.

AU - Iteld, B.

AU - Jafar, Z.

AU - Jain, A.

AU - Jamal, N.

AU - Kang, G.

AU - Karlsberg, R.

AU - Khanal, S.

AU - Khoury, S.

AU - Kieval, J.

AU - Kipperman, Robert

AU - Kluck, B.

AU - Kong, D.

AU - Kosinski, E.

AU - Kozak, M.

AU - Kozman, H.

AU - Kraft, P.

AU - Labroo, A.

AU - Lai, P.

AU - Lakkis, N.

AU - Lane, G.

AU - Laretta, B.

AU - Lee, D.

AU - Leesar, M.

AU - Leggett, J.

AU - Levine, M.

AU - Lieberman, S.

AU - Lim, M.

AU - Luber, J.

AU - Marques, V.

AU - Marzo, K.

AU - McGarvey, J.

AU - McKendall, G.

AU - McLellan, B.

AU - Meengs, M.

AU - Mego, D.

AU - Mehra, A.

AU - Messenger, J. A.

AU - Messenger, J. O.

AU - Midei, M.

AU - Miller, M.

AU - Moliterno, D.

AU - Momah, K.

AU - Mowdy, M.

AU - Nahhas, A.

AU - Navas, J.

AU - Niederman, A.

AU - Nygaard, T.

AU - O'Neill, W.

AU - Patel, K.

AU - Pfau, S.

AU - Pompili, V.

AU - Purdy, D.

AU - Reddy, B.

AU - Rees, A.

AU - Reiner, J.

AU - Riba, A.

AU - Rivera, E.

AU - Roberts, D.

AU - Rosenblatt, A.

AU - Rowe, W.

AU - Rowley, S.

AU - Rubin, D.

AU - Saeian, K.

AU - Saltiel, F.

AU - Sample, S.

AU - Sanchez, B.

AU - Sarembock, I.

AU - Saucedo, J.

AU - Schreiber, T.

AU - Shah, R.

AU - Singh, M.

AU - Slater, J.

AU - Small, R.

AU - Staniloae, C.

AU - Sundram, P. S.

AU - Swenson, L.

AU - Symkoviak, G.

AU - Tam, K.

AU - Taussig, A.

AU - Thatcher, J.

AU - Tolerico, P.

AU - Trippi, J.

AU - Turk, S.

AU - Van Osdol, K.

AU - Vicari, R.

AU - Virmani, A.

AU - Warner, M.

AU - Webel, R.

AU - Wertheimer, J.

AU - Williams, G.

AU - Williams, J.

AU - Winniford, M.

AU - Wohns, D.

AU - Zhao, D. X.M.

PY - 2007/1/3

Y1 - 2007/1/3

N2 - Context: Reperfusion with percutaneous transluminal coronary intervention (PCI) is effective at improving outcomes in patients with acute ST-elevation myocardial infarction (STEMI). However, in patients without prompt reestablishment of brisk coronary flow and tissue perfusion, mortality remains high, providing an opportunity for novel treatments, including anti-inflammatory agents. Objective: To evaluate the effectiveness of pexelizumab, a humanized monoclonal antibody that binds the C5 component of complement, as an adjunct to PCI in improving 30-day mortality from STEMI. Design, Setting, and Patients: This trial was a prospective, multicenter, double-blind, placebo-controlled, phase 3 study of the intravenous administration of pexelizumab in conjunction with primary PCI in STEMI with prespecified high-risk electrocardiographic findings. The trial was intended to enroll 8500 patients, but in conjunction with the US Food and Drug Administration enrollment was modified to 5745 patients presenting from 296 hospitals in 17 countries from July 13, 2004, to May 11, 2006. Interventions: Two thousand eight hundred eighty-five patients were randomly assigned to receive placebo and 2860 to receive pexelizumab given as a 2-mg/kg intravenous bolus prior to PCI followed by 0.05-mg/kg per hour infusion over the subsequent 24 hours. Patients were randomized within 6 hours of symptom onset. Main Outcome Measures: The primary end point was all-cause mortality through day 30. Secondary end points were death through day 90 and the composite of death, cardiogenic shock, or congestive heart failure through days 30 and 90. Results: No difference in mortality through day 30 was observed between the pexelizumab and placebo treatment groups, with 116 patients (4.06%) and 113 patients (3.92%) who died in the respective groups (hazard ratio [HR], 1.04; 95% confidence interval [CI], 0.80-1.35; log-rank P=.78). The composite end points of death, shock, or heart failure were also similar with 257 patients (8.99%) receiving pexelizumab and 265 patients (9.19%) receiving placebo at 30 days (HR, 0.98; 95% CI, 0.83-1.16; P=.81) and 293 patients (10.24%) receiving pexelizumab and 293 patients (10.16%) receiving placebo at 90 days (HR, 1.01; 95% CI, 0.86-1.19; P=.91). Conclusion: In this large clinical trial of patients treated with primary PCI for STEMI, mortality was low and unaffected by administration of pexelizumab.

AB - Context: Reperfusion with percutaneous transluminal coronary intervention (PCI) is effective at improving outcomes in patients with acute ST-elevation myocardial infarction (STEMI). However, in patients without prompt reestablishment of brisk coronary flow and tissue perfusion, mortality remains high, providing an opportunity for novel treatments, including anti-inflammatory agents. Objective: To evaluate the effectiveness of pexelizumab, a humanized monoclonal antibody that binds the C5 component of complement, as an adjunct to PCI in improving 30-day mortality from STEMI. Design, Setting, and Patients: This trial was a prospective, multicenter, double-blind, placebo-controlled, phase 3 study of the intravenous administration of pexelizumab in conjunction with primary PCI in STEMI with prespecified high-risk electrocardiographic findings. The trial was intended to enroll 8500 patients, but in conjunction with the US Food and Drug Administration enrollment was modified to 5745 patients presenting from 296 hospitals in 17 countries from July 13, 2004, to May 11, 2006. Interventions: Two thousand eight hundred eighty-five patients were randomly assigned to receive placebo and 2860 to receive pexelizumab given as a 2-mg/kg intravenous bolus prior to PCI followed by 0.05-mg/kg per hour infusion over the subsequent 24 hours. Patients were randomized within 6 hours of symptom onset. Main Outcome Measures: The primary end point was all-cause mortality through day 30. Secondary end points were death through day 90 and the composite of death, cardiogenic shock, or congestive heart failure through days 30 and 90. Results: No difference in mortality through day 30 was observed between the pexelizumab and placebo treatment groups, with 116 patients (4.06%) and 113 patients (3.92%) who died in the respective groups (hazard ratio [HR], 1.04; 95% confidence interval [CI], 0.80-1.35; log-rank P=.78). The composite end points of death, shock, or heart failure were also similar with 257 patients (8.99%) receiving pexelizumab and 265 patients (9.19%) receiving placebo at 30 days (HR, 0.98; 95% CI, 0.83-1.16; P=.81) and 293 patients (10.24%) receiving pexelizumab and 293 patients (10.16%) receiving placebo at 90 days (HR, 1.01; 95% CI, 0.86-1.19; P=.91). Conclusion: In this large clinical trial of patients treated with primary PCI for STEMI, mortality was low and unaffected by administration of pexelizumab.

UR - http://www.scopus.com/inward/record.url?scp=33845981823&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33845981823&partnerID=8YFLogxK

U2 - 10.1001/jama.297.1.43

DO - 10.1001/jama.297.1.43

M3 - Article

VL - 297

SP - 43

EP - 51

JO - JAMA - Journal of the American Medical Association

JF - JAMA - Journal of the American Medical Association

SN - 0002-9955

IS - 1

ER -