Penicillin Prophylaxis in Sickle Cell Disease (PROPS)

NCT ID: NCT00000585

Last Updated: 2016-03-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Study Classification: INTERVENTIONAL
• Study Start Date: 1983-08-31
• Study Completion Date: 1994-10-31

Brief Summary

To determine whether the regular daily administration of oral penicillin would reduce the incidence of documented infection due to Streptococcus pneumoniae in children with sickle cell anemia.

Detailed Description

BACKGROUND:

For over 20 years children with sickle cell anemia have been known to have an increased susceptibility to severe bacterial infection, particularly due to Streptococcus pneumoniae. Meningitis, pneumonia and septicemia due to this organism have been recognized as the major causes of death for these children, with children under three years of age being at highest risk. The annual incidence of pneumococcal septicemia among young children with sickle cell anemia appears to have remained remarkably constant over the last two decades at approximately 10 percent. This illness can often be fulminant, progressing from the onset of fever to death in less than 12 hours, with a case fatality rate ranging as high as 35 percent.

Penicillin prophylaxis has been advocated as a preventive measure against severe pneumococcal infections in children with sickle cell anemia. One study had shown that the risk of pneumococcal infection in these children could be reduced by the use of parenteral penicillin.

DESIGN NARRATIVE:

Phase I was a multi-center, randomized, double-blind, placebo-controlled trial. One hundred and five patients were assigned to the penicillin group and 110 to placebo. The primary endpoint was a documented severe infection due to S. pneumoniae. The secondary endpoint was a severe infection due to an organism other than S. pneumoniae.

Because data were not available to define the age at which prophylactic penicillin could be safely discontinued, the NHLBI launched Phase II of the Prophylactic Penicillin Study beginning in 1987. Recruitment ended in August, 1993. The clinical phase of Phase II ended in August, 1994.

Phase II was a multi-center randomized trial to evaluate the hazards of discontinuing daily oral penicillin at the age of five years. Within three months of their fifth birthdays, all children were randomized to continue oral penicillin prophylaxis or to stop prophylaxis. Each child was followed for a minimum of two years. The primary endpoint was a comparison of documented pneumococcal infection in children continuing penicillin after five years of age versus children whose prophylaxis was stopped at five years of age. Ancillary studies conducted in subsets of patients included: the prevalence of colonization of the nasopharynx with antibiotic resistant microorangisms; and the relationship of antibody response to pneumococcal vaccination to the incidence of pneumococcal sepsis in this patient population.

Conditions

Anemia, Sickle Cell; Hematologic Diseases; Hemoglobinopathies; Infection (S. Pneumoniae); Pneumonia

Study Design

• Allocation Method: RANDOMIZED
• Primary Study Purpose: PREVENTION
• Blinding Strategy: DOUBLE

Interventions

penicillin

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

In the Phase I trial, Black children with sickle cell anemia aged 3 months to 3 years. In the Phase II trial, children with sickle cell anemia aged five years 3 months of age and younger who had received prophylactic penicillin for at least two yea

• Maximum Eligible Age: 5 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role: lead

Principal Investigators

David Becton

Role:

University of Arkansas

Ann Bjornson

Role:

Gamble Institute of Medical Research

George Buchanan

Role:

University of Texas

Neil Grossman

Role:

Children's Hospital Medical Center, Cincinnati

C. Holbrook

Role:

East Carolina University School of Medicine

Rathyi Iyer

Role:

University of Mississippi Medical Center

Karen Kalinyak

Role:

Children's Hospital Medical Center, Cincinnati

Thomas Kinney

Role:

Duke University

Helen Maurer

Role:

University of Illinois at Chicago

Scott Miller

Role:

New York Health Science Center

Charles Pegelow

Role:

University of Miami

Sergio Piomelli

Role:

Columbia University

Gregory Reaman

Role:

Children's Hospital National Medical Center

Alan Schwartz

Role:

Washington University School of Medicine

Elliott Vichinsky

Role:

Children's Hospital & Medical Center

Winfred Wang

Role:

St. Jude Children's Research Hospital

Doris Wethers

Role:

St. Luke's Roosevelt Institute of Health Science

Gerald Woods

Role:

Children's Mercy Hospital Kansas City

References

Gaston MH, Verter JI, Woods G, Pegelow C, Kelleher J, Presbury G, Zarkowsky H, Vichinsky E, Iyer R, Lobel JS, et al. Prophylaxis with oral penicillin in children with sickle cell anemia. A randomized trial. N Engl J Med. 1986 Jun 19;314(25):1593-9. doi: 10.1056/NEJM198606193142501.

Reference Type: BACKGROUND

PMID: 3086721 (View on PubMed)

Falletta JM, Woods GM, Verter JI, Buchanan GR, Pegelow CH, Iyer RV, Miller ST, Holbrook CT, Kinney TR, Vichinsky E, et al. Discontinuing penicillin prophylaxis in children with sickle cell anemia. Prophylactic Penicillin Study II. J Pediatr. 1995 Nov;127(5):685-90. doi: 10.1016/s0022-3476(95)70154-0.

Reference Type: BACKGROUND

PMID: 7472817 (View on PubMed)

Bjornson AB, Falletta JM, Verter JI, Buchanan GR, Miller ST, Pegelow CH, Iyer RV, Johnstone HS, DeBaun MR, Wethers DL, Wang WC, Woods GM, Holbrook CT, Becton DL, Kinney TR, Reaman GH, Kalinyak K, Grossman NJ, Vichinsky E, Reid CD. Serotype-specific immunoglobulin G antibody responses to pneumococcal polysaccharide vaccine in children with sickle cell anemia: effects of continued penicillin prophylaxis. J Pediatr. 1996 Dec;129(6):828-35. doi: 10.1016/s0022-3476(96)70026-4.

Reference Type: BACKGROUND

PMID: 8969724 (View on PubMed)

Woods GM, Jorgensen JH, Waclawiw MA, Reid C, Wang W, Pegelow CH, Rogers ZR, Iyer RV, Holbrook CT, Kinney TR, Vichinsky E, DeBaun MR, Grossman NJ, Thomas MD, Falletta JM. Influence of penicillin prophylaxis on antimicrobial resistance in nasopharyngeal S. pneumoniae among children with sickle cell anemia. The Ancillary Nasopharyngeal Culture Study of Prophylactic Penicillin Study II. J Pediatr Hematol Oncol. 1997 Jul-Aug;19(4):327-33. doi: 10.1097/00043426-199707000-00011.

Reference Type: BACKGROUND

PMID: 9256832 (View on PubMed)

Gaston MH, Verter J. Sickle cell anaemia trial. Stat Med. 1990 Jan-Feb;9(1-2):45-9; discussion 49-51. doi: 10.1002/sim.4780090111.

Reference Type: BACKGROUND

PMID: 2111933 (View on PubMed)

Other Identifiers

305

Identifier Type: -

Identifier Source: org_study_id