Randomized Phase I Study of Trimetrexate Glucuronate (TMTX) With Leucovorin (LCV) Protection Plus Dapsone Versus Trimethoprim / Sulfamethoxazole (TMP/SMX) for Treatment of Moderately Severe Episodes of Pneumocystis Carinii Pneumonia

This study has been completed.
Sponsor:
Collaborator:
Jacobus Pharmaceutical
Information provided by:
NIH AIDS Clinical Trials Information Service
ClinicalTrials.gov Identifier:
NCT00002120
First received: November 2, 1999
Last updated: June 23, 2005
Last verified: March 1996
  Purpose

To evaluate the safety of the combination of trimetrexate glucuronate (TMTX) and dapsone with leucovorin protection versus trimethoprim/sulfamethoxazole (TMP/SMX) in patients with AIDS and moderately severe Pneumocystis carinii pneumonia (PCP). To determine the pharmacokinetic parameters of TMTX, leucovorin, and dapsone and of TMP/SMX when given to patients with AIDS and moderately severe PCP.


Condition Intervention Phase
Pneumonia, Pneumocystis Carinii
HIV Infections
Drug: Trimetrexate glucuronate
Drug: Trimethoprim
Drug: Sulfamethoxazole
Drug: Dapsone
Drug: Leucovorin calcium
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Pharmacokinetics Study
Masking: Double-Blind
Primary Purpose: Treatment
Official Title: Randomized Phase I Study of Trimetrexate Glucuronate (TMTX) With Leucovorin (LCV) Protection Plus Dapsone Versus Trimethoprim / Sulfamethoxazole (TMP/SMX) for Treatment of Moderately Severe Episodes of Pneumocystis Carinii Pneumonia

Resource links provided by NLM:


Further study details as provided by NIH AIDS Clinical Trials Information Service:

Estimated Enrollment: 20
  Eligibility

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

Inclusion Criteria

Concurrent Medication:

Allowed:

  • Empiric therapy for other opportunistic pulmonary infection (TB or fungi) for the first 72 hours of study enrollment ONLY, until presence of suspected pathogens can be confidently excluded.

Patients must have:

  • AIDS.
  • Confirmed diagnosis of PCP.
  • Alveolar-arterial differences in dissolved oxygen >= 35 mm Hg but < 55 mm Hg on room air.

Exclusion Criteria

Co-existing Condition:

Patients with the following symptoms or conditions are excluded:

  • Severe renal or hepatic dysfunction.
  • Serious or life-threatening intolerance to TMP/SMX, TMTX, or dapsone.
  • Concurrent pneumothorax.
  • Active pulmonary tuberculosis or other inadequately treated opportunistic pulmonary infection (e.g., Cryptococcus neoforms, CMV). NOTE:
  • Identification of Mycobacterium avium or CMV in sputum or BAL fluid does not exclude, since these organisms may be present without causing disease.
  • Pulmonary Kaposi's sarcoma.
  • Active opportunistic infections or malignancies requiring induction therapy with bone marrow suppressive drugs (e.g., ganciclovir) or hepatotoxic drugs (e.g., chemotherapy).
  • Unable to have arterial blood gases on room air obtained at baseline.
  • Unwilling to undergo bronchoscopy, if sputum induction does not reveal Pneumocystis carinii.
  • Suspected malabsorption (e.g., ileus or severe diarrhea with > 6 stools/day).
  • Known absence of G6PD activity.
  • Large volume (1.0 to 1.5 liters) of intravenous fluid (5 percent in water) per 24 hours is medically inadvisable.
  • Unwilling to comply with study design.

Concurrent Medication:

Excluded:

  • Induction therapy with bone marrow suppressive drugs (e.g., ganciclovir) or hepatotoxic drugs (e.g., chemotherapy).
  • AZT, ddI, ddC, d4T, or other antiretroviral therapy.

Patients with the following prior condition are excluded:

Prior history of serious or life-threatening intolerance to TMP/SMX. (NOTE:

  • Patients with less severe reactions may be included at the discretion of the investigator and primary care provider.)

Prior Medication:

Excluded:

  • More than 24 hours of systemic anti-PCP therapy within 2 weeks prior to study entry.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00002120

Locations
United States, California
Los Angeles County / Health Research Assoc / Drew Med Ctr
Los Angeles, California, United States, 90033
Sponsors and Collaborators
U.S. Bioscience
Jacobus Pharmaceutical
  More Information

No publications provided

ClinicalTrials.gov Identifier: NCT00002120     History of Changes
Other Study ID Numbers: 224A, TMTX A009
Study First Received: November 2, 1999
Last Updated: June 23, 2005
Health Authority: United States: Food and Drug Administration

Keywords provided by NIH AIDS Clinical Trials Information Service:
Trimethoprim-Sulfamethoxazole Combination
Trimetrexate
Pneumonia, Pneumocystis carinii
Leucovorin
Dapsone
Drug Therapy, Combination
Acquired Immunodeficiency Syndrome

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
Dapsone
Trimethoprim
Trimethoprim-Sulfamethoxazole Combination
Trimetrexate
Sulfamethoxazole
Leucovorin
Levoleucovorin
Antimalarials
Antiprotozoal Agents
Antiparasitic Agents
Anti-Infective Agents

ClinicalTrials.gov processed this record on April 17, 2014