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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00001013
First received: November 2, 1999
Last updated: March 15, 2012
Last verified: March 2012
  Purpose

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

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Estimated Enrollment: 364
Study Completion Date: September 1991
Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   12 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00001013

Locations
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
Sponsors and Collaborators
Investigators
Study Chair: Sattler FR
  More Information

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 April 16, 2014