Comparison of Trimetrexate Plus Leucovorin Calcium Rescue Versus Sulfamethoxazole-Trimethoprim in the Treatment of Pneumocystis Carinii Pneumonia (PCP) in Patients With AIDS

• Status: Completed
• Trial end date: 1991-09-01
• Target enrollment: 0
• Participant gender: All

Summary

To compare the safety and effectiveness of an investigational drug therapy (trimetrexate plus leucovorin calcium) with that of conventional therapy (sulfamethoxazole-trimethoprim) in the treatment of moderately severe Pneumocystis carinii pneumonia (PCP) in patients who have AIDS, are HIV positive, or are at high risk for HIV infection.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Treatments: Calcium; Calcium, Dietary; Leucovorin; Levoleucovorin; Pentamidine; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination; Trimetrexate

Criteria

Inclusion Criteria

Concurrent Medication:

Allowed:

• Acetaminophen:

• 650 mg prescribed as necessary for temperature > 38.7 degrees C. Acetaminophen should not be prescribed as a standing order for more than 48 hours.

Prior Medication:

Allowed:

• Zidovudine (AZT) as long as such therapy is suspended prior to randomization and not reinstituted until therapy for the acute episode is completed and the patient's white blood cell count is acceptable.

• Other myelosuppressive therapies which may be handled in the same manner as AZT.

• Prophylaxis for Pneumocystis carinii pneumonia (PCP).

• Unequivocal diagnosis of Pneumocystis carinii pneumonia (PCP) by morphologic confirmation of three or more typical P. carinii organisms in sputum, bronchoalveolar lavage fluid, or lung tissue obtained by transbronchial or open-lung biopsy within 3 days before or after randomization. If morphologic confirmation is not possible prior to therapy, patients may be randomized if the investigator believes there is a high suspicion of PCP based on clinical presentation. If morphologic diagnosis cannot be established within 6 days of randomization, the patient will be withdrawn from study therapy. Resting (A-a) DO2 < 30 torr on room air. Patient, parent, guardian, or person with power of attorney gives informed consent.

Exclusion Criteria

Co-existing Condition:

Patients will be excluded for the following reasons:

• History of Type I hypersensitivity (i.e., urticaria, angioedema, or anaphylaxis), exfoliative dermatitis, or other life-threatening reaction secondary to antibiotics containing sulfa, trimethoprim, or trimetrexate.

• History of life-threatening pentamidine toxicity.

Concurrent Medication:

Excluded:

• Other drugs for the treatment or prevention of AIDS or Pneumocystis carinii pneumonia (PCP).

• Disalcid.

• Aspirin.

• Acetaminophen q4h as a standing order for more than 48 hours.

Prior Medication:

Excluded within 14 days of study entry:

• Systemic steroids exceeding physiological replacement.

• Other investigational drugs including ganciclovir.

• Excluded within 6 weeks of study entry:

• Another antiprotozoal regimen for this episode for therapy of active Pneumocystis carinii pneumonia (PCP).

• Patients who are unable to have arterial blood gas analysis (ABG's) on room air.

• Patients for whom a liter of intravenous fluid (5 percent dextrose in water) per 24 hours, which is required to maintain blinding, would be medically inadvisable.