A Randomized, Comparative Study of Daily Dapsone and Daily Atovaquone for Prophylaxis Against PCP in HIV-Infected Patients Who Are Intolerant of Trimethoprim and/or Sulfonamides

HIV Infections Clinical Trial

Official title:

A Randomized, Comparative Study of Daily Dapsone and Daily Atovaquone for Prophylaxis Against PCP in HIV-Infected Patients Who Are Intolerant of Trimethoprim and/or Sulfonamides

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00000802
• Other study ID #: ACTG 277
• Secondary ID: CPCRA 03411253
• Status: Completed
• Phase: Phase 3
• Est. completion date: July 1997

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

To compare the efficacy and safety of dapsone versus atovaquone in preventing or delaying the onset of histologically proven or probable Pneumocystis carinii pneumonia in HIV-infected patients with CD4 counts <= 200 cells/mm3 or <= 15 percent of the total lymphocyte count who are intolerant to trimethoprim and/or sulfonamides.

Trimethoprim/sulfamethoxazole (TMP/SMX), which is effective for secondary PCP prophylaxis, is associated with allergic manifestations and side effects that limit its use. Patients who are intolerant of TMP/SMX require an effective alternative. Dapsone and atovaquone have both shown promise as PCP prophylactic agents.

Description:

Trimethoprim/sulfamethoxazole (TMP/SMX), which is effective for secondary PCP prophylaxis, is associated with allergic manifestations and side effects that limit its use. Patients who are intolerant of TMP/SMX require an effective alternative. Dapsone and atovaquone have both shown promise as PCP prophylactic agents.

Patients are randomized to receive either dapsone or atovaquone daily, with follow-up at the clinic every 4 months.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 700
• Est. completion date: July 1997
• Accepts healthy volunteers: No
• Gender: All
• Age group: 13 Years and older

Eligibility

Inclusion Criteria

Concurrent Medication: Strongly recommended:

• Pyrimethamine (50 mg) and folinic acid (15 mg) weekly in patients receiving dapsone who have CD4 count < 100 cells/mm3 and are toxoplasmosis seropositive.

Patients must have:

• Working diagnosis of HIV infection.

• CD4 count <= 200 cells/mm3 or <= 15 percent of total lymphocyte count at any time in the past OR a history of PCP.

• History of intolerance of trimethoprim and/or sulfonamides that required permanent discontinuation.

NOTE:

• Pregnant patients are eligible at the clinician's discretion.

Prior Medication:

Allowed:

• Prior PCP prophylaxis.

Exclusion Criteria

Co-existing Condition:

Patients with the following symptoms or conditions are excluded:

• Active pneumocystosis.

Concurrent Medication:

Excluded:

• PCP prophylaxis (other than study drug) or any medication with potential anti-PCP activity.

Patients with the following prior conditions are excluded:

• Known treatment-limiting reaction to dapsone or atovaquone.

Related Conditions & MeSH terms

• HIV Infections
• Pneumonia
• Pneumonia, Pneumocystis
• Pneumonia, Pneumocystis Carinii

Intervention

Drug:
• Atovaquone

• Dapsone

Locations

Country	Name	City	State
Tanzania	Mbeya Med. Research Program, Mbeya Referral Hosp. CRS	Mbeya
United States	Emory Univ. Hemophilia Program Office	Atlanta	Georgia
United States	University of Colorado Hospital CRS	Aurora	Colorado
United States	Johns Hopkins Adult AIDS CRS	Baltimore	Maryland
United States	Alabama Therapeutics CRS	Birmingham	Alabama
United States	Beth Israel Deaconess - East Campus A0102 CRS	Boston	Massachusetts
United States	Bmc Actg Crs	Boston	Massachusetts
United States	Massachusetts General Hospital ACTG CRS	Boston	Massachusetts
United States	SUNY - Buffalo, Erie County Medical Ctr.	Buffalo	New York
United States	Unc Aids Crs	Chapel Hill	North Carolina
United States	Carolinas HealthCare System, Carolinas Med. Ctr.	Charlotte	North Carolina
United States	Cook County Hosp. CORE Ctr.	Chicago	Illinois
United States	Northwestern University CRS	Chicago	Illinois
United States	Rush Univ. Med. Ctr. ACTG CRS	Chicago	Illinois
United States	Weiss Memorial Hosp.	Chicago	Illinois
United States	Univ. of Cincinnati CRS	Cincinnati	Ohio
United States	Case CRS	Cleveland	Ohio
United States	MetroHealth CRS	Cleveland	Ohio
United States	The Ohio State Univ. AIDS CRS	Columbus	Ohio
United States	Regional Center for Infectious Disease, Wendover Medical Center CRS	Greensboro	North Carolina
United States	Queens Med. Ctr.	Honolulu	Hawaii
United States	Univ. of Hawaii at Manoa, Leahi Hosp.	Honolulu	Hawaii
United States	Indiana Univ. School of Medicine, Infectious Disease Research Clinic	Indianapolis	Indiana
United States	Univ. of Iowa Healthcare, Div. of Infectious Diseases	Iowa City	Iowa
United States	USC CRS	Los Angeles	California
United States	Univ. of Miami AIDS CRS	Miami	Florida
United States	Hennepin County Med. Ctr., Div. of Infectious Diseases	Minneapolis	Minnesota
United States	University of Minnesota, ACTU	Minneapolis	Minnesota
United States	Beth Israel Med. Ctr. (Mt. Sinai)	New York	New York
United States	NY Univ. HIV/AIDS CRS	New York	New York
United States	Univ. of Nebraska Med. Ctr., Durham Outpatient Ctr.	Omaha	Nebraska
United States	Stanford CRS	Palo Alto	California
United States	Hosp. of the Univ. of Pennsylvania CRS	Philadelphia	Pennsylvania
United States	Wake County Health and Human Services CRS	Raleigh	North Carolina
United States	Univ. of Rochester ACTG CRS	Rochester	New York
United States	St. Louis ConnectCare, Infectious Diseases Clinic	Saint Louis	Missouri
United States	Washington U CRS	Saint Louis	Missouri
United States	Ucsd, Avrc Crs	San Diego	California
United States	Ucsf Aids Crs	San Francisco	California
United States	Santa Clara Valley Med. Ctr.	San Jose	California
United States	San Mateo County AIDS Program	San Mateo	California
United States	University of Washington AIDS CRS	Seattle	Washington
United States	Harbor-UCLA Med. Ctr. CRS	Torrance	California
United States	Howard University Hosp., Div. of Infectious Diseases, ACTU	Washington	District of Columbia

Sponsors (1)

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

Countries where clinical trial is conducted

United States,  Tanzania, 

References & Publications (3)

Caldwell P, Murphy R, Chan C, Yurik T, Scott J, el-Sadr W. Atovaquone suspension (ATQ) for prophylaxis of Pneumocystis carinii pneumonia (PCP): effects of baseline prophylaxis on safety and efficacy. Int Conf AIDS. 1998;12:297 (abstract no 22178)

El-Sadr WM, Murphy RL, Yurik TM, Luskin-Hawk R, Cheung TW, Balfour HH Jr, Eng R, Hooton TM, Kerkering TM, Schutz M, van der Horst C, Hafner R. Atovaquone compared with dapsone for the prevention of Pneumocystis carinii pneumonia in patients with HIV infection who cannot tolerate trimethoprim, sulfonamides, or both. Community Program for Clinical Research on AIDS and the AIDS Clinical Trials Group. N Engl J Med. 1998 Dec 24;339(26):1889-95. — View Citation

Murphy R, El-Sadr W, Cheung T, Luskin-Hawk R, Yurik T, Neaton J, Hafner R. Impact of protease inhibitor containing regimens on the risk of developing opportunistic infections and mortality in the CPCRA 034/ACTG 277 study. Conf Retroviruses Opportunistic Infect. 1998 Feb 1-5;5th:113 (abstract no 181)