Penicillin Prophylaxis in Sickle Cell Disease (PROPS)
Primary Purpose
Anemia, Sickle Cell, Hematologic Diseases, Hemoglobinopathies
Status
Completed
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
penicillin
Sponsored by
About this trial
This is an interventional prevention trial for Anemia, Sickle Cell
Eligibility 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
Sites / Locations
Outcomes
Primary Outcome Measures
Secondary Outcome Measures
Full Information
NCT ID
NCT00000585
First Posted
October 27, 1999
Last Updated
March 24, 2016
Sponsor
National Heart, Lung, and Blood Institute (NHLBI)
1. Study Identification
Unique Protocol Identification Number
NCT00000585
Brief Title
Penicillin Prophylaxis in Sickle Cell Disease (PROPS)
Study Type
Interventional
2. Study Status
Record Verification Date
October 1994
Overall Recruitment Status
Completed
Study Start Date
August 1983 (undefined)
Primary Completion Date
undefined (undefined)
Study Completion Date
October 1994 (undefined)
3. Sponsor/Collaborators
Name of the Sponsor
National Heart, Lung, and Blood Institute (NHLBI)
4. Oversight
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Anemia, Sickle Cell, Hematologic Diseases, Hemoglobinopathies, Infection (S. Pneumoniae), Pneumonia
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 3
Masking
Double
Allocation
Randomized
8. Arms, Groups, and Interventions
Intervention Type
Drug
Intervention Name(s)
penicillin
10. Eligibility
Sex
All
Maximum Age & Unit of Time
5 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
David Becton
Organizational Affiliation
University of Arkansas
First Name & Middle Initial & Last Name & Degree
Ann Bjornson
Organizational Affiliation
Gamble Institute of Medical Research
First Name & Middle Initial & Last Name & Degree
George Buchanan
Organizational Affiliation
University of Texas
First Name & Middle Initial & Last Name & Degree
Neil Grossman
Organizational Affiliation
Children's Hospital Medical Center, Cincinnati
First Name & Middle Initial & Last Name & Degree
C. Holbrook
Organizational Affiliation
East Carolina University School of Medicine
First Name & Middle Initial & Last Name & Degree
Rathyi Iyer
Organizational Affiliation
University of Mississippi Medical Center
First Name & Middle Initial & Last Name & Degree
Karen Kalinyak
Organizational Affiliation
Children's Hospital Medical Center, Cincinnati
First Name & Middle Initial & Last Name & Degree
Thomas Kinney
Organizational Affiliation
Duke University
First Name & Middle Initial & Last Name & Degree
Helen Maurer
Organizational Affiliation
University of Illinois at Chicago
First Name & Middle Initial & Last Name & Degree
Scott Miller
Organizational Affiliation
New York Health Science Center
First Name & Middle Initial & Last Name & Degree
Charles Pegelow
Organizational Affiliation
University of Miami
First Name & Middle Initial & Last Name & Degree
Sergio Piomelli
Organizational Affiliation
Columbia University
First Name & Middle Initial & Last Name & Degree
Gregory Reaman
Organizational Affiliation
Children's Hospital National Medical Center
First Name & Middle Initial & Last Name & Degree
Alan Schwartz
Organizational Affiliation
Washington University School of Medicine
First Name & Middle Initial & Last Name & Degree
Elliott Vichinsky
Organizational Affiliation
Children's Hospital & Medical Center
First Name & Middle Initial & Last Name & Degree
Winfred Wang
Organizational Affiliation
St. Jude Children's Research Hospital
First Name & Middle Initial & Last Name & Degree
Doris Wethers
Organizational Affiliation
St. Luke's Roosevelt Institute of Health Science
First Name & Middle Initial & Last Name & Degree
Gerald Woods
Organizational Affiliation
Children's Mercy Hospital Kansas City
12. IPD Sharing Statement
Citations:
PubMed Identifier
3086721
Citation
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.
Results Reference
background
PubMed Identifier
7472817
Citation
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.
Results Reference
background
PubMed Identifier
8969724
Citation
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.
Results Reference
background
PubMed Identifier
9256832
Citation
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.
Results Reference
background
PubMed Identifier
2111933
Citation
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.
Results Reference
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Penicillin Prophylaxis in Sickle Cell Disease (PROPS)
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