Comparison of Two Dosage Regimens of Oral Dapsone for Prophylaxis of Pneumocystis Carinii Pneumonia in Pediatric HIV Infection

HIV Infections Clinical Trial

Official title:

Comparison of Two Dosage Regimens of Oral Dapsone for Prophylaxis of Pneumocystis Carinii Pneumonia in Pediatric HIV Infection

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00000739
• Other study ID #: ACTG 179
• Secondary ID: 11154
• Status: Completed
• Phase: Phase 1
• Est. completion date: June 1998

Study information

• Verified date: October 2021
• Source: National Institute of Allergy and Infectious Diseases (NIAID)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Primary: To compare the toxicity of daily versus weekly dapsone in HIV-infected infants and children; to study the pharmacokinetics of orally administered dapsone in HIV-infected infants and children.

Secondary: To obtain information on the rate of Pneumocystis carinii pneumonia ( PCP ) breakthrough in children receiving two different dose regimens of dapsone.

Prophylaxis for Pneumocystis carinii pneumonia ( PCP ) is recommended for all HIV-infected children considered to be at high risk. Approximately 15 percent of children are intolerant to trimethoprim / sulfamethoxazole, the first choice drug for PCP prophylaxis. Since many children are also unable to take or tolerate aerosolized pentamidine, dapsone is a second choice for PCP prophylaxis. The most favorable dose regimen for dapsone has not been established.

Description:

Prophylaxis for Pneumocystis carinii pneumonia ( PCP ) is recommended for all HIV-infected children considered to be at high risk. Approximately 15 percent of children are intolerant to trimethoprim / sulfamethoxazole, the first choice drug for PCP prophylaxis. Since many children are also unable to take or tolerate aerosolized pentamidine, dapsone is a second choice for PCP prophylaxis. The most favorable dose regimen for dapsone has not been established.

Ninety-six HIV-infected infants and children who are intolerant to trimethoprim / sulfamethoxazole ( TMP / SMX ) are randomized to receive oral dapsone in a lower dose once daily or at a higher dose once weekly. Treatment continues until the last patient enrolled has received at least 3 months of therapy. Blood samples are drawn between weeks 4 and 8, at weeks 12 and 24, and every 3 months thereafter during dapsone administration.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 96
• Est. completion date: June 1998
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Month to 12 Years

Eligibility

Inclusion Criteria

Concurrent Medication:

Allowed:

• Rifampin and rifampin derivatives for up to 1 week during the study.

• Rifabutin or other drugs that could alter dapsone metabolism (if prescribed by the child's primary care physician).

Patients must have:

• Evidence of HIV infection.

PER AMENDMENT 11/16/95:

• Children who require prophylaxis. (Was written - Risk of developing PCP.)

• Known intolerance to TMP / SMX.

• Consent of parent or guardian. Patients entering this study may be co-enrolled in other ACTG pediatric studies.

Exclusion Criteria

Co-existing Condition:

Patients with the following symptoms and conditions are excluded:

• Glucose-6-phosphate dehydrogenase deficiency.

• Known allergy to dapsone.

Concurrent Medication:

Excluded:

• Rifampin, rifampin derivatives, or oxidant drugs for more than 1 week.

Patients with the following prior conditions are excluded:

• Serious or life-threatening reactions to TMP / SMX (e.g., anaphylaxis, Stevens-Johnson syndrome, hypotension) that would contraindicate therapy with sulfa drugs.

Prior Medication:

Excluded:

• Prior dapsone.

• Rifampin, rifampin derivatives, or oxidant drugs within 1 week prior to study entry.

• TMP / SMX within 7 days prior to study entry (and toxicity must be clearly resolving).

Prior Treatment:

Excluded:

• RBC transfusion within 4 weeks prior to study entry.

Related Conditions & MeSH terms

• Acquired Immunodeficiency Syndrome
• Communicable Diseases
• HIV Infections
• Infections
• Pneumonia
• Pneumonia, Pneumocystis
• Pneumonia, Pneumocystis Carinii

Intervention

Drug:
• Dapsone

Locations

Country	Name	City	State
Puerto Rico	Univ. Hosp. Ramón Ruiz Arnau, Dept. of Peds	Bayamon
Puerto Rico	San Juan City Hosp. PR NICHD CRS	San Juan
Puerto Rico	Univ. of Puerto Rico Ped. HIV/AIDS Research Program CRS	San Juan
United States	Emory Univ. School of Medicine, Dept. of Peds., Div. of Infectious Diseases	Atlanta	Georgia
United States	Univ. of Colorado Denver NICHD CRS	Aurora	Colorado
United States	BMC, Div. of Ped Infectious Diseases	Boston	Massachusetts
United States	HMS - Children's Hosp. Boston, Div. of Infectious Diseases	Boston	Massachusetts
United States	SUNY Downstate Med. Ctr., Children's Hosp. at Downstate NICHD CRS	Brooklyn	New York
United States	Med. Univ. of South Carolina, Div. of Ped. Infectious Diseases	Charleston	South Carolina
United States	Chicago Children's CRS	Chicago	Illinois
United States	Cook County Hosp.	Chicago	Illinois
United States	Univ. of Chicago - Dept. of Peds., Div. of Infectious Disease	Chicago	Illinois
United States	Univ. of Illinois College of Medicine at Chicago, Dept. of Peds	Chicago	Illinois
United States	Case CRS	Cleveland	Ohio
United States	Children's Hospital of Michigan NICHD CRS	Detroit	Michigan
United States	DUMC Ped. CRS	Durham	North Carolina
United States	North Shore-Long Island Jewish Health System, Dept. of Peds.	Great Neck	New York
United States	Univ. of Florida Jacksonville NICHD CRS	Jacksonville	Florida
United States	Long Beach Memorial Med. Ctr., Miller Children's Hosp.	Long Beach	California
United States	UCLA-Los Angeles/Brazil AIDS Consortium (LABAC) CRS	Los Angeles	California
United States	Usc La Nichd Crs	Los Angeles	California
United States	St. Jude/UTHSC CRS	Memphis	Tennessee
United States	Univ. of Miami Ped. Perinatal HIV/AIDS CRS	Miami	Florida
United States	UMDNJ - Robert Wood Johnson	New Brunswick	New Jersey
United States	Schneider Children's Hosp., Div. of Infectious Diseases	New Hyde Park	New York
United States	Tulane/LSU Maternal/Child CRS	New Orleans	Louisiana
United States	Columbia IMPAACT CRS	New York	New York
United States	Harlem Hosp. Ctr. NY NICHD CRS	New York	New York
United States	Incarnation Children's Ctr.	New York	New York
United States	NYU Med. Ctr., Dept. of Medicine	New York	New York
United States	Childrens Hosp. of the Kings Daughters	Norfolk	Virginia
United States	Children's Hosp. & Research Ctr. Oakland, Ped. Clinical Research Ctr. & Research Lab.	Oakland	California
United States	St. Joseph's Hosp. & Med. Ctr. of New Jersey	Paterson	New Jersey
United States	St. Christopher's Hosp. for Children	Philadelphia	Pennsylvania
United States	The Children's Hosp. of Philadelphia IMPAACT CRS	Philadelphia	Pennsylvania
United States	Strong Memorial Hospital Rochester NY NICHD CRS	Rochester	New York
United States	Univ. of Rochester ACTG CRS	Rochester	New York
United States	UCSD Maternal, Child, and Adolescent HIV CRS	San Diego	California
United States	UW School of Medicine - CHRMC	Seattle	Washington
United States	Baystate Health, Baystate Med. Ctr.	Springfield	Massachusetts
United States	SUNY Stony Brook NICHD CRS	Stony Brook	New York
United States	SUNY Upstate Med. Univ., Dept. of Peds.	Syracuse	New York
United States	Harbor - UCLA Med. Ctr. - Dept. of Peds., Div. of Infectious Diseases	Torrance	California
United States	Children's National Med. Ctr., ACTU	Washington	District of Columbia
United States	Howard Univ. Washington DC NICHD CRS	Washington	District of Columbia
United States	WNE Maternal Pediatric Adolescent AIDS CRS	Worcester	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)	Jacobus Pharmaceutical

Countries where clinical trial is conducted

United States,  Puerto Rico, 

References & Publications (4)

McIntosh K, Cooper E, Xu J, Mirochnick M, Lindsey J, Jacobus D, Mofenson L, Yogev R, Spector SA, Sullivan JL, Sacks H, Kovacs A, Nachman S, Sleasman J, Bonagura V, McNamara J. Toxicity and efficacy of daily vs. weekly dapsone for prevention of Pneumocystis carinii pneumonia in children infected with human immunodeficiency virus. ACTG 179 Study Team. AIDS Clinical Trials Group. Pediatr Infect Dis J. 1999 May;18(5):432-9. — View Citation

Mirochnick M, Cooper E, Mcintosh K. Pharmacokinetics of daily and weekly dapsone in HIV-infected children. ACTG Protocol 179 Team. American Pediatric Association and Society for Pediatric Research annual meeting; 1996 May 6-10; Washington, D.C. Pediatr AIDS HIV Infect. 1996 Aug;7(4):280 (unnumbered abstract)

Mirochnick M, Cooper E, McIntosh K. Pharmacokinetics of daily and weekly dapsone in HIV-infected children. Conf Retroviruses Opportunistic Infect. 1996 Jan 28-Feb 1;3rd:159

Perrier M, Schwarz T, Gonzalez O, Brounts S. Squamous cell carcinoma invading the right temporomandibular joint in a Belgian mare. Can Vet J. 2010 Aug;51(8):885-7. — View Citation