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

• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT00000739
• Collaborator: Jacobus Pharmaceutical (Industry)
• Enrollment: 96
• Locations: 46
• Patients Per Site: 2.1

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Pneumonia, Pneumocystis Carinii; HIV Infections	Drug: Dapsone	Phase 1

Detailed 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.

Study Design

• Study Type: Interventional
• Intervention Model: Parallel Assignment
• Primary Purpose: Treatment
• Official Title: Comparison of Two Dosage Regimens of Oral Dapsone for Prophylaxis of Pneumocystis Carinii Pneumonia in Pediatric HIV Infection
• Actual Study Completion Date: Jun 1, 1998

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

• Ages Eligible for Study: 1 Month to 12 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Long Beach Memorial Med. Ctr., Miller Children's Hosp.	Long Beach	California	United States	90801
2	Usc La Nichd Crs	Los Angeles	California	United States	90033
3	UCLA-Los Angeles/Brazil AIDS Consortium (LABAC) CRS	Los Angeles	California	United States	90095
4	Children's Hosp. & Research Ctr. Oakland, Ped. Clinical Research Ctr. & Research Lab.	Oakland	California	United States	94609
5	UCSD Maternal, Child, and Adolescent HIV CRS	San Diego	California	United States	92093
6	Harbor - UCLA Med. Ctr. - Dept. of Peds., Div. of Infectious Diseases	Torrance	California	United States	90502
7	Univ. of Colorado Denver NICHD CRS	Aurora	Colorado	United States	80218
8	Children's National Med. Ctr., ACTU	Washington	District of Columbia	United States	20010
9	Howard Univ. Washington DC NICHD CRS	Washington	District of Columbia	United States	20060
10	Univ. of Florida Jacksonville NICHD CRS	Jacksonville	Florida	United States	32209
11	Univ. of Miami Ped. Perinatal HIV/AIDS CRS	Miami	Florida	United States	33161
12	Emory Univ. School of Medicine, Dept. of Peds., Div. of Infectious Diseases	Atlanta	Georgia	United States	30306
13	Cook County Hosp.	Chicago	Illinois	United States	60612
14	Chicago Children's CRS	Chicago	Illinois	United States	60614
15	Univ. of Chicago - Dept. of Peds., Div. of Infectious Disease	Chicago	Illinois	United States	60637
16	Univ. of Illinois College of Medicine at Chicago, Dept. of Peds	Chicago	Illinois	United States
17	Tulane/LSU Maternal/Child CRS	New Orleans	Louisiana	United States	70112
18	HMS - Children's Hosp. Boston, Div. of Infectious Diseases	Boston	Massachusetts	United States	02115
19	BMC, Div. of Ped Infectious Diseases	Boston	Massachusetts	United States	02118
20	Baystate Health, Baystate Med. Ctr.	Springfield	Massachusetts	United States	01199
21	WNE Maternal Pediatric Adolescent AIDS CRS	Worcester	Massachusetts	United States	01655
22	Children's Hospital of Michigan NICHD CRS	Detroit	Michigan	United States	48201
23	UMDNJ - Robert Wood Johnson	New Brunswick	New Jersey	United States	08903
24	St. Joseph's Hosp. & Med. Ctr. of New Jersey	Paterson	New Jersey	United States	07103
25	SUNY Downstate Med. Ctr., Children's Hosp. at Downstate NICHD CRS	Brooklyn	New York	United States	11203
26	North Shore-Long Island Jewish Health System, Dept. of Peds.	Great Neck	New York	United States	11021
27	Schneider Children's Hosp., Div. of Infectious Diseases	New Hyde Park	New York	United States	11040
28	NYU Med. Ctr., Dept. of Medicine	New York	New York	United States	10016
29	Columbia IMPAACT CRS	New York	New York	United States	10032
30	Incarnation Children's Ctr.	New York	New York	United States	10032
31	Harlem Hosp. Ctr. NY NICHD CRS	New York	New York	United States	10037
32	Univ. of Rochester ACTG CRS	Rochester	New York	United States	14642
33	Strong Memorial Hospital Rochester NY NICHD CRS	Rochester	New York	United States
34	SUNY Stony Brook NICHD CRS	Stony Brook	New York	United States	11794
35	SUNY Upstate Med. Univ., Dept. of Peds.	Syracuse	New York	United States	13210
36	DUMC Ped. CRS	Durham	North Carolina	United States	27710
37	Case CRS	Cleveland	Ohio	United States
38	The Children's Hosp. of Philadelphia IMPAACT CRS	Philadelphia	Pennsylvania	United States	19104
39	St. Christopher's Hosp. for Children	Philadelphia	Pennsylvania	United States	19134
40	Med. Univ. of South Carolina, Div. of Ped. Infectious Diseases	Charleston	South Carolina	United States	2942
41	St. Jude/UTHSC CRS	Memphis	Tennessee	United States	38105
42	Childrens Hosp. of the Kings Daughters	Norfolk	Virginia	United States	23507
43	UW School of Medicine - CHRMC	Seattle	Washington	United States	98105
44	Univ. Hosp. Ramón Ruiz Arnau, Dept. of Peds	Bayamon		Puerto Rico
45	San Juan City Hosp. PR NICHD CRS	San Juan		Puerto Rico	00936
46	Univ. of Puerto Rico Ped. HIV/AIDS Research Program CRS	San Juan		Puerto Rico

Sponsors and Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID)
• Jacobus Pharmaceutical

Investigators

• Study Chair: McIntosh K,
• Study Chair: Cooper E,

Study Documents (Full-Text)

None provided.

More Information

Publications

• 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.
• 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.

• Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
• ClinicalTrials.gov Identifier: NCT00000739
• Other Study ID Numbers: ACTG 179; 11154
• First Posted: Aug 31, 2001
• Last Update Posted: Nov 4, 2021
• Last Verified: Oct 1, 2021

• Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID): Pneumonia, Pneumocystis carinii; Dapsone; Acquired Immunodeficiency Syndrome; AIDS-Related Complex; Drug Administration Schedule
• Additional relevant MeSH terms: Infections; Communicable Diseases; Pneumonia; HIV Infections; Acquired Immunodeficiency Syndrome; Pneumonia, Pneumocystis; Dapsone

Study Results

No Results Posted as of Nov 4, 2021