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

Condition(s) targeted: Pneumonia, Pneumocystis Carinii; HIV Infections

Intervention: Sulfamethoxazole-Trimethoprim (Drug)

Phase: Phase 4

Status: Completed

Sponsored by: National Institute of Allergy and Infectious Diseases (NIAID)

Official(s) and/or principal investigator(s):
Para MF, Study Chair
Dohn MN, Study Chair
Frame P, Study Chair

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.

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

Study design: Primary Purpose: Treatment

Detailed 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.

Minimum age: 13 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

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.

San Juan City Hosp. PR NICHD CRS, San Juan 00936, Puerto Rico

Mbeya Med. Research Program, Mbeya Referral Hosp. CRS, Mbeya, Tanzania

USC CRS, Los Angeles, California 90033, United States

Stanford CRS, Palo Alto, California 94305, United States

Ucsf Aids Crs, San Francisco, California 94110, United States

Santa Clara Valley Med. Ctr., San Jose, California, United States

San Mateo County AIDS Program, San Mateo, California, United States

Harbor-UCLA Med. Ctr. CRS, Torrance, California 90502, United States

University of Colorado Hospital CRS, Aurora, Colorado 80262, United States

Univ. of Florida Jacksonville NICHD CRS, Jacksonville, Florida 32209, United States

Univ. of Miami AIDS CRS, Miami, Florida 33136, United States

Queens Med. Ctr., Honolulu, Hawaii 96816, United States

Univ. of Hawaii at Manoa, Leahi Hosp., Honolulu, Hawaii 96816, United States

Cook County Hosp. CORE Ctr., Chicago, Illinois 60612, United States

Northwestern University CRS, Chicago, Illinois 60611, United States

Rush Univ. Med. Ctr. ACTG CRS, Chicago, Illinois 60612, United States

Indiana Univ. School of Medicine, Infectious Disease Research Clinic, Indianapolis, Indiana 46202, United States

Methodist Hosp. of Indiana, Indianapolis, Indiana 46202, United States

Tulane/LSU Maternal/Child CRS, New Orleans, Louisiana 70112, United States

Johns Hopkins Adult AIDS CRS, Baltimore, Maryland 21287, United States

Beth Israel Deaconess - East Campus A0102 CRS, Boston, Massachusetts 02215, United States

Beth Israel Deaconess Med. Ctr., ACTG CRS, Boston, Massachusetts 02215, United States

Bmc Actg Crs, Boston, Massachusetts 02118, United States

Massachusetts General Hospital ACTG CRS, Boston, Massachusetts 02114, United States

Hennepin County Med. Ctr., Div. of Infectious Diseases, Minneapolis, Minnesota 55415, United States

University of Minnesota, ACTU, Minneapolis, Minnesota 55455, United States

St. Louis ConnectCare, Infectious Diseases Clinic, St Louis, Missouri 63112, United States

Washington U CRS, St. Louis, Missouri, United States

Univ. of Nebraska Med. Ctr., Durham Outpatient Ctr., Omaha, Nebraska 68198, United States

SUNY - Buffalo, Erie County Medical Ctr., Buffalo, New York 14215, United States

Beth Israel Med. Ctr. (Mt. Sinai), New York, New York 10029, United States

NY Univ. HIV/AIDS CRS, New York, New York 10016, United States

Univ. of Rochester ACTG CRS, Rochester, New York, United States

Unc Aids Crs, Chapel Hill, North Carolina 27599, United States

Carolinas HealthCare System, Carolinas Med. Ctr., Charlotte, North Carolina 28203, United States

Regional Center for Infectious Disease, Wendover Medical Center CRS, Greensboro, North Carolina 27401, United States

Univ. of Cincinnati CRS, Cincinnati, Ohio 45267, United States

Case CRS, Cleveland, Ohio, United States

MetroHealth CRS, Cleveland, Ohio 44109, United States

The Ohio State Univ. AIDS CRS, Columbus, Ohio 43210, United States

Hosp. of the Univ. of Pennsylvania CRS, Philadelphia, Pennsylvania 19104, United States

University of Washington AIDS CRS, Seattle, Washington 98122, United States

Click here for more information about sulfamethoxazole-trimethoprim

Related publications:

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.

Last updated: April 13, 2012