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

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID) (NIH)

Overall Status

Completed

CT.gov ID

NCT00000816

Collaborator

Glaxo Wellcome (Industry)

370

Enrollment

Locations

8.8

Patients Per Site

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Pneumonia, Pneumocystis Carinii HIV Infections	Drug: Sulfamethoxazole-Trimethoprim	Phase 4

Detailed Description

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.

Study Design

Study Type:

Interventional

Primary Purpose:

Treatment

Official Title:

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

Actual Study Completion Date :

Sep 1, 1996

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

13 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	USC CRS	Los Angeles	California	United States	90033
2	Stanford CRS	Palo Alto	California	United States	94305
3	Ucsf Aids Crs	San Francisco	California	United States	94110
4	Santa Clara Valley Med. Ctr.	San Jose	California	United States
5	San Mateo County AIDS Program	San Mateo	California	United States
6	Harbor-UCLA Med. Ctr. CRS	Torrance	California	United States	90502
7	University of Colorado Hospital CRS	Aurora	Colorado	United States	80262
8	Univ. of Florida Jacksonville NICHD CRS	Jacksonville	Florida	United States	32209
9	Univ. of Miami AIDS CRS	Miami	Florida	United States	33136
10	Queens Med. Ctr.	Honolulu	Hawaii	United States	96816
11	Univ. of Hawaii at Manoa, Leahi Hosp.	Honolulu	Hawaii	United States	96816
12	Northwestern University CRS	Chicago	Illinois	United States	60611
13	Cook County Hosp. CORE Ctr.	Chicago	Illinois	United States	60612
14	Rush Univ. Med. Ctr. ACTG CRS	Chicago	Illinois	United States	60612
15	Indiana Univ. School of Medicine, Infectious Disease Research Clinic	Indianapolis	Indiana	United States	46202
16	Methodist Hosp. of Indiana	Indianapolis	Indiana	United States	46202
17	Tulane/LSU Maternal/Child CRS	New Orleans	Louisiana	United States	70112
18	Johns Hopkins Adult AIDS CRS	Baltimore	Maryland	United States	21287
19	Massachusetts General Hospital ACTG CRS	Boston	Massachusetts	United States	02114
20	Bmc Actg Crs	Boston	Massachusetts	United States	02118
21	Beth Israel Deaconess - East Campus A0102 CRS	Boston	Massachusetts	United States	02215
22	Beth Israel Deaconess Med. Ctr., ACTG CRS	Boston	Massachusetts	United States	02215
23	Hennepin County Med. Ctr., Div. of Infectious Diseases	Minneapolis	Minnesota	United States	55415
24	University of Minnesota, ACTU	Minneapolis	Minnesota	United States	55455
25	St. Louis ConnectCare, Infectious Diseases Clinic	Saint Louis	Missouri	United States	63112
26	Washington U CRS	Saint Louis	Missouri	United States
27	Univ. of Nebraska Med. Ctr., Durham Outpatient Ctr.	Omaha	Nebraska	United States	68198
28	SUNY - Buffalo, Erie County Medical Ctr.	Buffalo	New York	United States	14215
29	NY Univ. HIV/AIDS CRS	New York	New York	United States	10016
30	Beth Israel Med. Ctr. (Mt. Sinai)	New York	New York	United States	10029
31	Univ. of Rochester ACTG CRS	Rochester	New York	United States
32	Unc Aids Crs	Chapel Hill	North Carolina	United States	27599
33	Carolinas HealthCare System, Carolinas Med. Ctr.	Charlotte	North Carolina	United States	28203
34	Regional Center for Infectious Disease, Wendover Medical Center CRS	Greensboro	North Carolina	United States	27401
35	Univ. of Cincinnati CRS	Cincinnati	Ohio	United States	45267
36	MetroHealth CRS	Cleveland	Ohio	United States	44109
37	Case CRS	Cleveland	Ohio	United States
38	The Ohio State Univ. AIDS CRS	Columbus	Ohio	United States	43210
39	Hosp. of the Univ. of Pennsylvania CRS	Philadelphia	Pennsylvania	United States	19104
40	University of Washington AIDS CRS	Seattle	Washington	United States	98122
41	San Juan City Hosp. PR NICHD CRS	San Juan		Puerto Rico	00936
42	Mbeya Med. Research Program, Mbeya Referral Hosp. CRS	Mbeya		Tanzania