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

This study has been completed.
Sponsor:
Collaborator:
Glaxo Wellcome
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00000816
First received: November 2, 1999
Last updated: April 13, 2012
Last verified: April 2012
  Purpose

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 Intervention Phase
Pneumonia, Pneumocystis Carinii
HIV Infections
Drug: Sulfamethoxazole-Trimethoprim
Phase 4

Study Type: Interventional
Study Design: Primary Purpose: Treatment
Official Title: Gradual Initiation of Trimethoprim/Sulfamethoxazole as Primary Pneumocystis Carinii Pneumonia Prophylaxis

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Estimated Enrollment: 370
Study Completion Date: September 1996
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.

  Eligibility

Ages Eligible for Study:   13 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00000816

  Show 42 Study Locations
Sponsors and Collaborators
Glaxo Wellcome
Investigators
Study Chair: Para MF
Study Chair: Dohn MN
Study Chair: Frame P
  More Information

Additional Information:
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)

Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00000816     History of Changes
Other Study ID Numbers: ACTG 268, 11244
Study First Received: November 2, 1999
Last Updated: April 13, 2012
Health Authority: United States: Federal Government

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Trimethoprim-Sulfamethoxazole Combination
Pneumonia, Pneumocystis carinii
Acquired Immunodeficiency Syndrome
AIDS-Related Complex
Sulfamethoxazole-Trimethoprim

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Pneumonia
Pneumonia, Pneumocystis
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Lung Diseases
Respiratory Tract Diseases
Respiratory Tract Infections
Lung Diseases, Fungal
Mycoses
Pneumocystis Infections
Sulfamethoxazole
Trimethoprim
Trimethoprim-Sulfamethoxazole Combination
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Anti-Infective Agents, Urinary
Renal Agents
Antimalarials
Antiprotozoal Agents
Antiparasitic Agents

ClinicalTrials.gov processed this record on August 20, 2014