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

NCT ID: NCT00000816

Last Updated: 2021-11-04

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE4

Total Enrollment

370 participants

Study Classification

INTERVENTIONAL

Study Completion Date

1996-09-30

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Pneumonia, Pneumocystis Carinii HIV Infections

Keywords

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Trimethoprim-Sulfamethoxazole Combination Pneumonia, Pneumocystis carinii Acquired Immunodeficiency Syndrome AIDS-Related Complex Sulfamethoxazole-Trimethoprim

Study Design

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Primary Study Purpose

TREATMENT

Interventions

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Sulfamethoxazole-Trimethoprim

Intervention Type DRUG

Eligibility Criteria

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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.
Minimum Eligible Age

13 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Glaxo Wellcome

INDUSTRY

Sponsor Role collaborator

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Para MF

Role: STUDY_CHAIR

Dohn MN

Role: STUDY_CHAIR

Frame P

Role: STUDY_CHAIR

Locations

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USC CRS

Los Angeles, California, United States

Site Status

Stanford CRS

Palo Alto, California, United States

Site Status

Ucsf Aids Crs

San Francisco, California, United States

Site Status

Santa Clara Valley Med. Ctr.

San Jose, California, United States

Site Status

San Mateo County AIDS Program

San Mateo, California, United States

Site Status

Harbor-UCLA Med. Ctr. CRS

Torrance, California, United States

Site Status

University of Colorado Hospital CRS

Aurora, Colorado, United States

Site Status

Univ. of Florida Jacksonville NICHD CRS

Jacksonville, Florida, United States

Site Status

Univ. of Miami AIDS CRS

Miami, Florida, United States

Site Status

Queens Med. Ctr.

Honolulu, Hawaii, United States

Site Status

Univ. of Hawaii at Manoa, Leahi Hosp.

Honolulu, Hawaii, United States

Site Status

Northwestern University CRS

Chicago, Illinois, United States

Site Status

Cook County Hosp. CORE Ctr.

Chicago, Illinois, United States

Site Status

Rush Univ. Med. Ctr. ACTG CRS

Chicago, Illinois, United States

Site Status

Indiana Univ. School of Medicine, Infectious Disease Research Clinic

Indianapolis, Indiana, United States

Site Status

Methodist Hosp. of Indiana

Indianapolis, Indiana, United States

Site Status

Tulane/LSU Maternal/Child CRS

New Orleans, Louisiana, United States

Site Status

Johns Hopkins Adult AIDS CRS

Baltimore, Maryland, United States

Site Status

Massachusetts General Hospital ACTG CRS

Boston, Massachusetts, United States

Site Status

Bmc Actg Crs

Boston, Massachusetts, United States

Site Status

Beth Israel Deaconess - East Campus A0102 CRS

Boston, Massachusetts, United States

Site Status

Beth Israel Deaconess Med. Ctr., ACTG CRS

Boston, Massachusetts, United States

Site Status

Hennepin County Med. Ctr., Div. of Infectious Diseases

Minneapolis, Minnesota, United States

Site Status

University of Minnesota, ACTU

Minneapolis, Minnesota, United States

Site Status

St. Louis ConnectCare, Infectious Diseases Clinic

St Louis, Missouri, United States

Site Status

Washington U CRS

St Louis, Missouri, United States

Site Status

Univ. of Nebraska Med. Ctr., Durham Outpatient Ctr.

Omaha, Nebraska, United States

Site Status

SUNY - Buffalo, Erie County Medical Ctr.

Buffalo, New York, United States

Site Status

NY Univ. HIV/AIDS CRS

New York, New York, United States

Site Status

Beth Israel Med. Ctr. (Mt. Sinai)

New York, New York, United States

Site Status

Univ. of Rochester ACTG CRS

Rochester, New York, United States

Site Status

Unc Aids Crs

Chapel Hill, North Carolina, United States

Site Status

Carolinas HealthCare System, Carolinas Med. Ctr.

Charlotte, North Carolina, United States

Site Status

Regional Center for Infectious Disease, Wendover Medical Center CRS

Greensboro, North Carolina, United States

Site Status

Univ. of Cincinnati CRS

Cincinnati, Ohio, United States

Site Status

MetroHealth CRS

Cleveland, Ohio, United States

Site Status

Case CRS

Cleveland, Ohio, United States

Site Status

The Ohio State Univ. AIDS CRS

Columbus, Ohio, United States

Site Status

Hosp. of the Univ. of Pennsylvania CRS

Philadelphia, Pennsylvania, United States

Site Status

University of Washington AIDS CRS

Seattle, Washington, United States

Site Status

San Juan City Hosp. PR NICHD CRS

San Juan, , Puerto Rico

Site Status

Mbeya Med. Research Program, Mbeya Referral Hosp. CRS

Mbeya, , Tanzania

Site Status

Countries

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United States Puerto Rico Tanzania

References

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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)

Reference Type BACKGROUND

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. doi: 10.1097/00126334-200008010-00007.

Reference Type BACKGROUND
PMID: 11015150 (View on PubMed)

Other Identifiers

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11244

Identifier Type: REGISTRY

Identifier Source: secondary_id

ACTG 268

Identifier Type: -

Identifier Source: org_study_id