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

• Register: ClinicalTrials.gov
• Last refreshed on: 17 October 2012
• Main ID: NCT00002120
• Date of registration: 02/11/1999
• Primary sponsor: U.S. Bioscience
• Public 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
• Scientific 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
• Date of first enrolment: January 1976
• Target sample size: 20
• Recruitment status: Completed
• URL: http://clinicaltrials.gov/show/NCT00002120
• Study type: Interventional
• Study design: Endpoint Classification: Pharmacokinetics Study, Masking: Double-Blind, Primary Purpose: Treatment

Countries of recruitment

United States

Key inclusion & exclusion 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.



Age minimum: 13 Years
Age maximum: N/A
Gender: Both

Health Condition(s) or Problem(s) studied

HIV Infections

Pneumonia, Pneumocystis Carinii

Intervention(s)

Drug: Dapsone

Drug: Leucovorin calcium

Drug: Sulfamethoxazole

Drug: Trimethoprim

Drug: Trimetrexate glucuronate

Secondary ID(s)

224A

TMTX A009

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Jacobus Pharmaceutical