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

NCT ID: NCT00001013

Last Updated: 2021-11-04

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

364 participants

Study Classification

INTERVENTIONAL

Study Completion Date

1991-09-30

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Pneumonia, Pneumocystis Carinii HIV Infections

Keywords

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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

Study Design

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Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Interventions

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Trimetrexate glucuronate

Intervention Type DRUG

Pentamidine isethionate

Intervention Type DRUG

Sulfamethoxazole-Trimethoprim

Intervention Type DRUG

Leucovorin calcium

Intervention Type DRUG

Eligibility Criteria

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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.
Minimum Eligible Age

12 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Sattler FR

Role: STUDY_CHAIR

Locations

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Los Angeles County - USC Med Ctr

Los Angeles, California, United States

Site Status

George Washington Univ Med Ctr

Washington D.C., District of Columbia, United States

Site Status

Univ of Miami School of Medicine

Miami, Florida, United States

Site Status

Northwestern Univ Med School

Chicago, Illinois, United States

Site Status

Charity Hosp / Tulane Univ Med School

New Orleans, Louisiana, United States

Site Status

Louisiana State Univ Med Ctr / Tulane Med School

New Orleans, Louisiana, United States

Site Status

Tulane Univ School of Medicine

New Orleans, Louisiana, United States

Site Status

Univ of Massachusetts Med Ctr

Worcester, Massachusetts, United States

Site Status

SUNY / Erie County Med Ctr at Buffalo

Buffalo, New York, United States

Site Status

City Hosp Ctr at Elmhurst / Mount Sinai Hosp

Elmhurst, New York, United States

Site Status

Beth Israel Med Ctr / Peter Krueger Clinic

New York, New York, United States

Site Status

Mount Sinai Med Ctr

New York, New York, United States

Site Status

Univ of Rochester Medical Center

Rochester, New York, United States

Site Status

SUNY - Stony Brook

Stony Brook, New York, United States

Site Status

SUNY / State Univ of New York

Syracuse, New York, United States

Site Status

Bronx Municipal Hosp Ctr/Jacobi Med Ctr

The Bronx, New York, United States

Site Status

Jack Weiler Hosp / Bronx Municipal Hosp

The Bronx, New York, United States

Site Status

Montefiore Med Ctr / Bronx Municipal Hosp

The Bronx, New York, United States

Site Status

Holmes Hosp / Univ of Cincinnati Med Ctr

Cincinnati, Ohio, United States

Site Status

Univ Hosp of Cleveland / Case Western Reserve Univ

Cleveland, Ohio, United States

Site Status

Milton S Hershey Med Ctr

Hershey, Pennsylvania, United States

Site Status

Thomas Jefferson Med College

Philadelphia, Pennsylvania, United States

Site Status

Julio Arroyo

West Columbia, South Carolina, United States

Site Status

Countries

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United States

References

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Sattler FR, Frame P, Davis R, Nichols L, Shelton B, Akil B, Baughman R, Hughlett C, Weiss W, Boylen CT, et al. Trimetrexate with leucovorin versus trimethoprim-sulfamethoxazole for moderate to severe episodes of Pneumocystis carinii pneumonia in patients with AIDS: a prospective, controlled multicenter investigation of the AIDS Clinical Trials Group Protocol 029/031. J Infect Dis. 1994 Jul;170(1):165-72. doi: 10.1093/infdis/170.1.165.

Reference Type BACKGROUND
PMID: 8014493 (View on PubMed)

Other Identifiers

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11005

Identifier Type: REGISTRY

Identifier Source: secondary_id

ACTG 029

Identifier Type: -

Identifier Source: org_study_id