NCT00000724

Brief Summary

To study the safety and effectiveness of trimetrexate (TMTX) plus leucovorin calcium rescue (LCV) in the treatment of Pneumocystis carinii pneumonia (PCP) in patients who have AIDS, patients who are HIV positive, or those for whom laboratory confirmation of HIV infection has not yet been established if they are at high risk for HIV infection, and who have not responded to standard treatments or who have demonstrated severe or life-threatening intolerance to both conventional therapies for PCP. The drugs trimethoprim / sulfamethoxazole (TMP / SMX) and pentamidine, usually used to treat PCP in AIDS patients, have proven ineffective in many patients and have had to be discontinued in many other patients because of severe side effects. TMTX was chosen for this trial because it was found to be very active against the PCP organism in laboratory tests and, in a preliminary trial in combination with LCV, there was a high response rate without severe toxicity.

Trial Health

80
On Track

Trial Health Score

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

Geographic Reach
1 country

1 active site

Status
completed

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

Trial Relationships

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Study Timeline

Key milestones and dates

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
2.8 years until next milestone

Study Completion

Last participant's last visit for all outcomes

July 1, 2004

Completed
Last Updated

December 19, 2012

Status Verified

December 1, 2012

First QC Date

November 2, 1999

Last Update Submit

December 18, 2012

Conditions

Pneumonia, Pneumocystis CariniiHIV Infections

Keywords

TrimetrexatePneumonia, Pneumocystis cariniiInjections, IntravenousLeucovorinDrug EvaluationDrug Therapy, CombinationFolic Acid AntagonistsAcquired Immunodeficiency SyndromeAntiprotozoal Agents

Interventions

Trimetrexate glucuronateDRUG
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:
  • Antihypertensive agents.
  • Concurrent Treatment:
  • Allowed:
  • Blood products.
  • Ventilatory support.
  • Prior Medication:
  • Required:
  • At least 7 days trimethoprim / sulfamethoxazole or parenteral pentamidine.
  • Allowed:
  • Myelosuppressive or nephrotoxic agents including zidovudine, but must be discontinued during trial.
  • No improvement in ventilatory status, defined as no change or a decrease in arterial or alveolar difference ((A-a) DO2) in the 72 hours prior to entry. (A-a) DO2 should be determined on room air, or receiving an FiO2 of 100 percent for 10 minutes via a tightly fitting non-rebreathing mask, or at an FiO2 of 100 percent for 10 minutes if the patient is being ventilated. Intolerance to TMP / SMX is defined as one or more of the following:
  • Platelets \< 50000 platelets/mm3 or absolute neutrophil count (polys + bands) = or \< 500 cells/mm3 on at least two occasions = or \> 12 hours apart.
  • Blistering rash, mucosal involvement, generalized maculopapular eruption or intolerable pruritus.
  • +10 more criteria

You may not qualify if:

  • Co-existing Condition:
  • Patients with the following are excluded:
  • History of Type I hypersensitivity (i.e., urticaria, angioedema, or anaphylaxis), exfoliative dermatitis, or other life-threatening reactions due to trimetrexate.
  • Patients with less severe adverse reactions may be enrolled if, in the opinion of the investigator, they do not prohibit rechallenge with the drug.
  • Concurrent Medication:
  • Excluded:
  • Myelosuppressive or nephrotoxic agents.
  • Other investigational drugs including high-dose steroids (exceeding physiologic replacement doses).
  • Patients with the following are excluded:
  • History of Type I hypersensitivity (i.e., urticaria, angioedema, or anaphylaxis), exfoliative dermatitis, or other life-threatening reactions due to trimetrexate.
  • Patients with less severe adverse reactions may be enrolled if, in the opinion of the investigator, they do not prohibit rechallenge with the drug.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Warner-Lambert Parke-Davis

Morris Plains, New Jersey, 07950, United States

Location

Related Publications (1)

  • Feinberg J, McDermott C, Nutter J. Trimetrexate (TMTX) salvage therapy for PCP in AIDS patients with limited therapeutic options. Int Conf AIDS. 1992 Jul 19-24;8(2):B136 (abstract no PoB 3297)

    BACKGROUND

MeSH Terms

Conditions

Pneumonia, PneumocystisHIV InfectionsAcquired Immunodeficiency Syndrome

Interventions

trimetrexate glucuronateLeucovorin

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 DiseasesSlow Virus Diseases

Intervention Hierarchy (Ancestors)

FormyltetrahydrofolatesTetrahydrofolatesFolic AcidPterinsPteridinesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingHeterocyclic CompoundsCoenzymesEnzymes and Coenzymes

Study Officials

  • Feinberg J

    STUDY CHAIR

Study Design

Study Type
interventional
Phase
phase 3
Masking
NONE
Purpose
TREATMENT
Sponsor Type
NIH

Study Record Dates

First Submitted

November 2, 1999

First Posted

August 31, 2001

Study Completion

July 1, 2004

Last Updated

December 19, 2012

Record last verified: 2012-12

Locations

US(1)