Comparison of Trimetrexate Plus Leucovorin Calcium Rescue Versus Sulfamethoxazole-Trimethoprim in the Treatment of Pneumocystis Carinii Pneumonia (PCP) in Patients With AIDS
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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.
Condition | Intervention | Phase |
---|---|---|
Pneumonia, Pneumocystis Carinii HIV Infections |
Drug: Trimetrexate glucuronate Drug: Pentamidine isethionate Drug: Sulfamethoxazole-Trimethoprim Drug: Leucovorin calcium |
Phase 3 |
Study Type: | Interventional |
Study Design: | Intervention Model: Parallel Assignment Primary Purpose: Treatment |
Official Title: | A Randomized, Comparative, Double-Blind Trial of Trimetrexate (CI-898) With Leucovorin Calcium Rescue Versus Trimethoprim / Sulfamethoxazole for Moderately Severe Pneumocystis Carinii Pneumonia in Patients With AIDS |
Estimated Enrollment: | 364 |
Study Completion Date: | September 1991 |
New treatments are needed to reduce the mortality rate from PCP in AIDS patients and to reduce the high relapse rate found after conventional therapy. Trimetrexate (TMTX) was chosen for this trial because it was found to be much more potent than sulfamethoxazole/trimethoprim (SMX/TMP) against the PCP organism in laboratory tests. Also TMTX, in combination with leucovorin (LCV), did not cause severe toxicity in a preliminary trial. It is believed that TMTX will be more effective than SMX/TMP in treating PCP and in preventing a recurrence of PCP. Preliminary studies suggest that aerosolized pentamidine (PEN) is likely to be effective in preventing a recurrence of PCP.
Patients entered in the study are randomly assigned to TMTX / LCV or to SMX/TMP for a 21-day trial. For the first 10 days, the trial is double-blind (neither patient nor physician knows which drugs the patient is receiving), and drugs are given by intravenous infusion. TMTX is given once every 24 hours and LCV every 6 hours; SMX/TMP is given every 6 hours. Doses are determined by body size. After the first 10 days, LCV and SMX/TMP may be given orally. Doses are adjusted or treatment is changed to intravenous PEN if side effects are too severe. During the 21-day trial, zidovudine (AZT) may not be used because of possible increased bone marrow toxicity. AZT may be resumed as soon as the patient's white cell count is acceptable. Aerosolized PEN therapy is begun 7 - 10 days after completion of therapy for the acute episode. PEN is inhaled once weekly for 4 weeks, then every 2 weeks for 48 weeks.
Ages Eligible for Study: | 12 Years and older |
Genders Eligible for Study: | Both |
Accepts Healthy Volunteers: | No |
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.
United States, California | |
Los Angeles County - USC Med Ctr | |
Los Angeles, California, United States, 90033 | |
United States, District of Columbia | |
George Washington Univ Med Ctr | |
Washington, District of Columbia, United States, 20037 | |
United States, Florida | |
Univ of Miami School of Medicine | |
Miami, Florida, United States, 331361013 | |
United States, Illinois | |
Northwestern Univ Med School | |
Chicago, Illinois, United States, 60611 | |
United States, Louisiana | |
Charity Hosp / Tulane Univ Med School | |
New Orleans, Louisiana, United States, 70112 | |
Louisiana State Univ Med Ctr / Tulane Med School | |
New Orleans, Louisiana, United States, 70112 | |
Tulane Univ School of Medicine | |
New Orleans, Louisiana, United States, 70112 | |
United States, Massachusetts | |
Univ of Massachusetts Med Ctr | |
Worcester, Massachusetts, United States, 01655 | |
United States, New York | |
Montefiore Med Ctr / Bronx Municipal Hosp | |
Bronx, New York, United States, 10467 | |
Jack Weiler Hosp / Bronx Municipal Hosp | |
Bronx, New York, United States, 10465 | |
Bronx Municipal Hosp Ctr/Jacobi Med Ctr | |
Bronx, New York, United States, 10461 | |
SUNY / Erie County Med Ctr at Buffalo | |
Buffalo, New York, United States, 14215 | |
City Hosp Ctr at Elmhurst / Mount Sinai Hosp | |
Elmhurst, New York, United States, 11373 | |
Mount Sinai Med Ctr | |
New York, New York, United States, 10029 | |
Beth Israel Med Ctr / Peter Krueger Clinic | |
New York, New York, United States, 10003 | |
Univ of Rochester Medical Center | |
Rochester, New York, United States, 14642 | |
SUNY - Stony Brook | |
Stony Brook, New York, United States, 117948153 | |
SUNY / State Univ of New York | |
Syracuse, New York, United States, 13210 | |
United States, Ohio | |
Holmes Hosp / Univ of Cincinnati Med Ctr | |
Cincinnati, Ohio, United States, 452670405 | |
Univ Hosp of Cleveland / Case Western Reserve Univ | |
Cleveland, Ohio, United States, 44106 | |
United States, Pennsylvania | |
Milton S Hershey Med Ctr | |
Hershey, Pennsylvania, United States, 170330850 | |
Thomas Jefferson Med College | |
Philadelphia, Pennsylvania, United States, 19107 | |
United States, South Carolina | |
Julio Arroyo | |
West Columbia, South Carolina, United States, 29169 |
Study Chair: | Sattler FR |
Additional Information:
Publications:
Responsible Party: | National Institute of Allergy and Infectious Diseases (NIAID) |
ClinicalTrials.gov Identifier: | NCT00001013 History of Changes |
Other Study ID Numbers: | ACTG 029, 11005 |
Study First Received: | November 2, 1999 |
Last Updated: | March 15, 2012 |
Health Authority: | United States: Federal Government |
Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Trimethoprim-Sulfamethoxazole Combination Trimetrexate AIDS-Related Opportunistic Infections Pneumonia, Pneumocystis carinii Pentamidine Infusions, Intravenous Leucovorin |
Drug Therapy, Combination Folic Acid Antagonists Aerosols Acquired Immunodeficiency Syndrome Antiprotozoal Agents AIDS-Related Complex Sulfamethoxazole-Trimethoprim |
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 Antiprotozoal Agents Pentamidine Trimethoprim Trimethoprim-Sulfamethoxazole Combination Calcium, Dietary Folic Acid Antagonists Trimetrexate Leucovorin Levoleucovorin Sulfamethoxazole Antiparasitic Agents |
ClinicalTrials.gov processed this record on March 14, 2013