NCT00001014

Brief 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. 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 in treating PCP and in preventing a recurrence of PCP.

Trial Health

80
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
302

participants targeted

Target at P50-P75 for phase_3

Geographic Reach
1 country

6 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Completion

Last participant's last visit for all outcomes

September 1, 1991

Completed
8.2 years until next milestone

First Submitted

Initial submission to the registry

November 2, 1999

Completed
1.8 years until next milestone

First Posted

Study publicly available on registry

August 31, 2001

Completed
Last Updated

November 4, 2021

Status Verified

October 1, 2021

First QC Date

November 2, 1999

Last Update Submit

October 28, 2021

Conditions

Pneumonia, Pneumocystis CariniiHIV Infections

Keywords

Trimethoprim-Sulfamethoxazole CombinationTrimetrexateAIDS-Related Opportunistic InfectionsPneumonia, Pneumocystis cariniiInfusions, IntravenousLeucovorinDrug Therapy, CombinationAdministration, OralAcquired Immunodeficiency SyndromeAntiprotozoal AgentsAIDS-Related ComplexSulfamethoxazole-Trimethoprim

Interventions

Trimetrexate glucuronateDRUG
Sulfamethoxazole-TrimethoprimDRUG
Leucovorin calciumDRUG

Eligibility Criteria

Age12 Years+
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

  • Concurrent Medication:
  • Allowed:
  • Acetaminophen 650 mg prescribed as necessary for temperature \> 38.7 degrees C. Acetaminophen q4h should not be prescribed as a standing order for more than 48 hours.
  • Prior Medication:
  • Allowed:
  • Zidovudine as long as such therapy is suspended prior to randomization and not reinstituted until therapy for the acute episode is completed.
  • 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 alveolar-arterial oxygen differences = or \> 30 mm Hg on room air.

You may not qualify if:

  • Patients with the following are excluded:
  • Inability to have alveolar blood gas analysis on room air.
  • Medically unable to receive a liter of intravenous fluid (5 percent dextrose in water) per 24 hours. This procedure is required in order to maintain blinding.
  • Prior Medication:
  • Excluded within 14 days of study entry:
  • Systemic steroids exceeding physiological replacement.
  • Other investigational drugs.
  • Excluded within 6 weeks of study entry:
  • Antiprotozoal regimen for this episode consisting of pentamidine, eflornithine, DFMO, or dapsone, for therapy of active Pneumocystis carinii pneumonia (PCP)
  • 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.
  • Requirement for treatment with agents that are known to be myelosuppressive or nephrotoxic during the period of acute Pneumocystis carinii pneumonia (PCP) therapy.
  • Other drugs for the treatment or prevention of AIDS or Pneumocystis carinii pneumonia (PCP); disulcid; aspirin; acetaminophen q4h for more than 48 hours.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (6)

Ucsf Aids Crs

San Francisco, California, 94110, United States

Location

Rush Univ. Med. Ctr. ACTG CRS

Chicago, Illinois, 60611, United States

Location

Tulane Med. Ctr. - Charity Hosp. of New Orleans, ACTU

New Orleans, Louisiana, 70112, United States

Location

Washington U CRS

St Louis, Missouri, United States

Location

SUNY - Buffalo, Erie County Medical Ctr.

Buffalo, New York, 14215, United States

Location

Case CRS

Cleveland, Ohio, 44106, United States

Location

Related Publications (1)

  • 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.

    PMID: 8014493BACKGROUND

MeSH Terms

Conditions

Pneumonia, PneumocystisHIV InfectionsAIDS-Related Opportunistic InfectionsAcquired Immunodeficiency SyndromeAIDS-Related Complex

Interventions

trimetrexate glucuronateTrimethoprim, Sulfamethoxazole Drug CombinationLeucovorin

Condition Hierarchy (Ancestors)

Lung Diseases, FungalMycosesBacterial Infections and MycosesInfectionsPneumocystis InfectionsRespiratory Tract InfectionsPneumoniaLung DiseasesRespiratory Tract DiseasesBlood-Borne InfectionsCommunicable DiseasesSexually Transmitted Diseases, ViralSexually Transmitted DiseasesLentivirus InfectionsRetroviridae InfectionsRNA Virus InfectionsVirus DiseasesGenital DiseasesUrogenital DiseasesImmunologic Deficiency SyndromesImmune System DiseasesOpportunistic InfectionsSlow Virus Diseases

Intervention Hierarchy (Ancestors)

SulfamethoxazoleBenzenesulfonamidesSulfonamidesAmidesOrganic ChemicalsSulfanilamidesAniline CompoundsAminesBenzene DerivativesHydrocarbons, AromaticHydrocarbons, CyclicHydrocarbonsSulfonesSulfur CompoundsTrimethoprimPyrimidinesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsDrug CombinationsPharmaceutical PreparationsFormyltetrahydrofolatesTetrahydrofolatesFolic AcidPterinsPteridinesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingCoenzymesEnzymes and Coenzymes

Study Officials

  • Sattler FR

    STUDY CHAIR

Study Design

Study Type
interventional
Phase
phase 3
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
NIH
Responsible Party
SPONSOR

Study Record Dates

First Submitted

November 2, 1999

First Posted

August 31, 2001

Study Completion

September 1, 1991

Last Updated

November 4, 2021

Record last verified: 2021-10

Locations

US(6)