Palivizumab prophylaxis reduces hospitalization due to respiratory syncytial virus in young children with hemodynamically significant congenital heart disease

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Abstract

Objectives

To evaluate the safety, tolerance, and efficacy of palivizumab in children with hemodynamically significant congenital heart disease (CHD).

Study design

A randomized, double-blind, placebo-controlled trial included 1287 children with CHD randomly assigned 1:1 to receive 5 monthly intramuscular injections of 15 mg/kg palivizumab or placebo. Children were followed for 150 days. The primary efficacy end point was antigen-confirmed respiratory syncytial virus (RSV) hospitalization.

Results

Palivizumab recipients had a 45% relative reduction in RSV hospitalizations (P = .003), a 56% reduction in total days of RSV hospitalization per 100 children (P = .003), and a 73% reduction in total RSV hospital days with increased supplemental oxygen per 100 children (P = .014). Adverse events were similar in the treatment groups; no child had drug discontinued for a related adverse event. Serious adverse events occurred in 55.4% of palivizumab recipients and 63.1% of placebo recipients (P<.005); none were related to palivizumab. Twenty-one children (3.3%) in the palivizumab group and 27 (4.2%) in the placebo group died; no deaths were attributed to palivizumab. The rates of cardiac surgeries performed earlier than planned were similar in the treatment groups.

Conclusions

Monthly palivizumab (15 mg/kg IM) was safe, well-tolerated, and effective for prophylaxis of serious RSV disease in young children with hemodynamically significant CHD.

Section snippets

Design and patient population

This was a multicenter, randomized, double-blind, placebo-controlled trial in children with CHD. The study was conducted during 4 consecutive RSV seasons, 1998 through 2002. Each child participated during only one season. The local institutional review board or independent ethics committee approved the study protocol, and parents or guardians gave written informed consent before participation. The study was conducted at 76 centers in the United States (n = 47), Canada (n = 6), Sweden (n = 3), Germany

Results

Starting on November 1 and ending on or before December 31 of each year between 1998 and 2001, a total of 1287 patients were randomly assigned. Study sites in the United States and Canada randomly assigned 800 (62.2%) and 133 (10.3%) children, respectively. The remaining children were randomly assigned in Poland (150, 11.6%), the United Kingdom (95, 7.4%), Germany (49, 3.8%), Sweden (33, 2.6%), and France (27, 2.1%). From 1 to 45 patients were randomly assigned per site, with an average of 17

Discussion

This large, placebo-controlled trial demonstrates the benefit of palivizumab prophylaxis in children with CHD. Children receiving prophylaxis had a 45% (95% CI: 23, 67) relative reduction in RSV hospitalization. These results are consistent with the IMpact-RSV trial in children with prematurity with or without chronic lung disease, in which a 55% (95% CI: 38, 72) relative reduction was observed.14 The reduction in RSV hospitalization rate was evident in both the cyanotic (7.9% placebo vs 5.6%

Acknowledgements

We thank W. Ripley Ballou, MD, James F. Balsley, MD, PhD, Bernard Landry, MPH, Judith Scott, MPH, Peggy McDonald, RN, Lori Ovington, Ray Hsieh, Rong Ye, and Kevin Crawford of MedImmune, Inc, for their contributions to this study; Barbara Shepherd, PhD, of MedImmune, Inc, for assistance in preparation of the manuscript; Virginia Capps, Randi Gower, Patricia Keegan, and the clinical monitoring and data management/biostatistics staff at PPD Development, Inc; the clinical research staff at all the

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Supported by MedImmune, Inc.

The members of the Cardiac Synagis Study Group appear in the Appendix.

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