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

Sponsor

U.S. Bioscience (Industry)

Overall Status

Completed

CT.gov ID

NCT00002120

Collaborator

Jacobus Pharmaceutical (Industry)

Enrollment

Location

Study Details

Study Description

Brief Summary

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 or Disease	Intervention/Treatment	Phase
Pneumonia, Pneumocystis Carinii HIV Infections	Drug: Trimetrexate glucuronate Drug: Trimethoprim Drug: Sulfamethoxazole Drug: Dapsone Drug: Leucovorin calcium	Phase 1

Study Design

Study Type:

Interventional

Masking:

Double

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

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

13 Years to 0 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.