A Randomized, Double-Blind Study of 566C80 Versus Septra (Sulfamethoxazole/Trimethoprim) for the Treatment of Pneumocystis Carinii Pneumonia in AIDS Patients

This study has been completed.
Sponsor:
Collaborator:
Glaxo Wellcome
Information provided by:
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00000655
First received: November 2, 1999
Last updated: February 25, 2011
Last verified: February 2011
  Purpose

To evaluate the effectiveness of atovaquone (566C80) compared to a standard antipneumocystis agent, (SMX/TMP), for the treatment of mild to moderate Pneumocystis carinii pneumonia (PCP) in AIDS patients. To compare the safety of short-term (21 days) treatment with 566C80 and SMX/TMP in AIDS patients with an acute episode of PCP.

Standard therapies for acute treatment of PCP involve either SMX/TMP or pentamidine isetionate. Although both treatments are equally effective, side effects prevent completion of therapy in 11-55 percent of patients.


Condition Intervention Phase
Pneumonia, Pneumocystis Carinii
HIV Infections
Drug: Atovaquone
Drug: Sulfamethoxazole-Trimethoprim
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Primary Purpose: Treatment
Official Title: A Randomized, Double-Blind Study of 566C80 Versus Septra (Trimethoprim/Sulfamethoxazole) for the Treatment of Pneumocystis Carinii Pneumonia in AIDS Patients

Resource links provided by NLM:


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

Estimated Enrollment: 300
Primary Completion Date: January 1992 (Final data collection date for primary outcome measure)
Detailed Description:

Standard therapies for acute treatment of PCP involve either SMX/TMP or pentamidine isetionate. Although both treatments are equally effective, side effects prevent completion of therapy in 11-55 percent of patients.

Patients are randomized into one of two treatment groups to receive either (1) 566C80 for 21 days, or (2) SMX/TMP for 21 days. Patients will be stratified according to severity of PCP. Group A will be those with an arterial-alveolar (A-a) DO2 < 35 mm Hg. Group B will have an A-a DO2 of 35-45 mm Hg., and will also be required to receive therapy with Corticosteroids. All doses are taken with food. During the 21 days of treatment, patients are examined clinically for adverse effects and have hematology (blood-related) and clinical chemistry studies conducted a minimum of 2 times weekly. More frequent monitoring may be required at the discretion of the investigator. To evaluate the effectiveness of study medication, the clinical status of each patient is evaluated 2 to 3 times per week (e.g., dyspnea score, cough score, chest tightness/pain score, vital signs). Also, on days 7 and 21 of treatment, an arterial blood gas measurement and chest X-ray are performed. Patients who experience severe toxicities will be discontinued from the study and placed on alternative therapy. Patients will also be removed from study if they show significant clinical deterioration within the first 7 days of therapy or if there is no improvement after 10 days of therapy. This study involves a double placebo with one group randomized to receive oral 566C80 and placebo tablets which look like SMX/TMP while the other group will receive SMX/TMP and placebo tablets looking like 566C80.

  Eligibility

Ages Eligible for Study:   13 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

Patient must have the following:

  • Presumptive diagnosis of AIDS as defined by the CDC.
  • Untreated Pneumocystis carinii pneumonia (PCP).
  • Willingness and ability to give informed consent.

Prior Medication:

Allowed:

  • Prophylactic therapy for Pneumocystis carinii pneumonia (PCP) including aerosolized pentamidine or sulfamethoxazole/trimethoprim (SMX/TMP) (at a dose no greater than two DS tablets twice daily).

Exclusion Criteria

Co-existing Condition:

Patients with the following conditions or symptoms are excluded:

  • Judged by the investigator to be in impending respiratory failure.
  • Malabsorption or vomiting that would, in the judgment of investigator, potentially limit the retention and absorption of an oral therapy.
  • Concurrent bacterial, fungal, or viral pneumonitis, pulmonary Kaposi's sarcoma or other concurrent illness, or chronic pulmonary disease that, in the investigator's opinion, would make interpretation of drug efficacy difficult.

Concurrent Medication:

Excluded:

  • Corticosteroid treatment (except replacement therapy or patients in Group B).
  • Ganciclovir.
  • Zidovudine (AZT).
  • Investigational agents including antiretroviral agents (didanosine (ddI), dideoxycytidine (ddC), etc.).

Drugs likely to have anti-pneumocystis effect such as:

  • Sulfonamides.
  • Pentamidine.
  • Dapsone.
  • Trimethoprim.
  • Other DHFR inhibitors.
  • Primaquine.
  • Clindamycin.
  • Sulfonylureas.

Patients with the following are excluded:

  • Judged by the investigator to be in impending respiratory failure.
  • Prior therapy for this episode of PCP or treatment within 4 weeks of entry for a prior episode of PCP.
  • Unable to or refuse to discontinue zidovudine, ganciclovir, or other antiretroviral agents during the 21 day treatment period.
  • Unable to take medication orally or unwilling or unable to take study medication with food.
  • Significant psychosis or emotional disorder such that, in the investigator's opinion, the patient would not be compliant with the study protocol.
  • Prior documented glucose-6-phosphate dehydrogenase (G6PD) deficiency.
  • Prior history of life-threatening toxicity to SMX/TMP such as severe rash or Stevens-Johnson syndrome.

Prior Medication:

Excluded:

  • Prior therapy for this episode of Pneumocystis carinii pneumonia (PCP) or treatment within 4 weeks for a prior episode of PCP.
  • Blood transfusions.
  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: NCT00000655

  Show 38 Study Locations
Sponsors and Collaborators
Glaxo Wellcome
Investigators
Study Chair: Hughes WT
  More Information

Additional Information:
Publications:
Hughes W, et al. Comparison of 566C80 & trimethoprim-sulfamethoxazole (TMP-SMZ) for the treatment of P. carinii pneumonitis (PCP). An International Multicenter, CCTG & ACTG Collaboration. Int Conf AIDS. 1992 Jul 19-24;8(1):We48 (abstract no WeB 1019)

ClinicalTrials.gov Identifier: NCT00000655     History of Changes
Other Study ID Numbers: ACTG 167, NIAID 90-CC-185, Protocol #03, FDA 53A, Project P71
Study First Received: November 2, 1999
Last Updated: February 25, 2011
Health Authority: United States: Federal Government

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

Additional relevant MeSH terms:
Infection
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

ClinicalTrials.gov processed this record on September 18, 2014