Gradual Initiation of Sulfamethoxazole/Trimethoprim as Primary Pneumocystis Carinii Pneumonia Prophylaxis

HIV Infections Clinical Trial

Official title:

Gradual Initiation of Trimethoprim/Sulfamethoxazole as Primary Pneumocystis Carinii Pneumonia Prophylaxis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00000816
• Other study ID #: ACTG 268
• Secondary ID: 11244
• Status: Completed
• Phase: Phase 4
• Est. completion date: September 1996

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 determine whether gradual initiation of sulfamethoxazole/trimethoprim (SMX/TMP) reduces the incidence of treatment-limiting adverse reactions compared to the routine initiation of the drugs for Pneumocystis carinii pneumonia (PCP) prophylaxis in HIV-infected patients.

Although a number of clinical trials have demonstrated the superiority of SMX/TMP for PCP prophylaxis, the incidence of adverse reactions to this medication is high. In a pilot study in which patients were initiated with SMX/TMP prophylaxis by gradually increasing the dose over 2 weeks, no significant adverse reactions have occurred.

Description:

Although a number of clinical trials have demonstrated the superiority of SMX/TMP for PCP prophylaxis, the incidence of adverse reactions to this medication is high. In a pilot study in which patients were initiated with SMX/TMP prophylaxis by gradually increasing the dose over 2 weeks, no significant adverse reactions have occurred.

Patients are randomized to receive either gradually increasing doses of SMX/TMP suspension or routine daily initiation of SMX/TMP double strength (DS) tablets for 2 weeks. All patients will then be switched over to receive open-label SMX/TMP DS tablets daily for 10 weeks.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 370
• Est. completion date: September 1996
• Accepts healthy volunteers: No
• Gender: All
• Age group: 13 Years and older

Eligibility

Inclusion Criteria

Concurrent Medication:

Allowed if clinically indicated:

• Recombinant erythropoietin (rEPO) and G-CSF.

Allowed for symptomatic treatment of mild study drug toxicity:

• Antipyretics and analgesics (ibuprofen).

• Antihistamines (diphenhydramine HCl).

• Terfenadine or astemizole (but not allowed with concomitant antifungal or macrolide use).

• Systemic steroids.

Patients must have:

• HIV infection.

• CD4 count <= 250 cells/mm3 OR history or presence of thrush.

• No history of confirmed or probable pneumocystosis.

NOTE:

• Pregnant women are not excluded, but safety issues should be discussed with patient prior to enrollment.

• This study is appropriate for prisoner participation.

• Coenrollment in ongoing ACTG antiretroviral studies is permitted provided no new study drugs are added to the patient's drug regimen for 4 weeks before or after initiation of SMX/TMP.

Prior Medication:

Allowed:

• Prior aerosolized pentamidine and dapsone for primary PCP prophylaxis.

Exclusion Criteria

Co-existing Condition:

Patients with the following symptoms or conditions are excluded:

• Known adverse reactions to sulfa, trimethoprim, or SMX/TMP.

• Inability to comply with dosing schedule or complete dosing record.

Concurrent Medication:

Excluded:

• Procysteine.

• Glutathione.

• N-acetylcysteine (NAC).

• Antihistamines (unless used for symptomatic treatment of study drug toxicity).

• Systemic corticosteroids (unless used for replacement purposes).

• Leucovorin calcium (unless used for symptomatic treatment of study drug toxicity).

• TMP or sulfa drugs outside of the study.

Prior Medication:

Excluded at any time:

• Prior SMX/TMP as primary PCP prophylaxis.

Excluded within 4 weeks prior to study entry:

• Initiation of antiretroviral agents.

• Initiation of anti-infective agents (including SMX/TMP for another indication).

Excluded within 2 weeks prior to study entry:

• Antihistamines.

• Procysteine.

• Glutathione.

• N-acetylcysteine (NAC).

• Systemic corticosteroids (unless used for replacement purposes).

• Leucovorin calcium.

• TMP and sulfa drugs separately.

Related Conditions & MeSH terms

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

Intervention

Drug:
• Sulfamethoxazole-Trimethoprim

Locations

Country	Name	City	State
Puerto Rico	San Juan City Hosp. PR NICHD CRS	San Juan
Tanzania	Mbeya Med. Research Program, Mbeya Referral Hosp. CRS	Mbeya
United States	University of Colorado Hospital CRS	Aurora	Colorado
United States	Johns Hopkins Adult AIDS CRS	Baltimore	Maryland
United States	Beth Israel Deaconess - East Campus A0102 CRS	Boston	Massachusetts
United States	Beth Israel Deaconess Med. Ctr., ACTG 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	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	Methodist Hosp. of Indiana	Indianapolis	Indiana
United States	Univ. of Florida Jacksonville NICHD CRS	Jacksonville	Florida
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	Tulane/LSU Maternal/Child CRS	New Orleans	Louisiana
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	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	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

Sponsors (2)

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

Countries where clinical trial is conducted

United States,  Puerto Rico,  Tanzania, 

References & Publications (2)

Para MF, Dohn M, Frame P, Becker S, Finkelstein D, Walawander A. ACTG 268 trial - gradual initiation of trimethoprim/sulfamethoxazole (T/S) as primary prophylaxis for Pneumocystis carinii pneumonia (PCP). Conf Retroviruses Opportunistic Infect. 1997 Jan 22-26;4th:65 (abstract no 2)

Para MF, Finkelstein D, Becker S, Dohn M, Walawander A, Black JR. Reduced toxicity with gradual initiation of trimethoprim-sulfamethoxazole as primary prophylaxis for Pneumocystis carinii pneumonia: AIDS Clinical Trials Group 268. J Acquir Immune Defic Syndr. 2000 Aug 1;24(4):337-43. — View Citation