NCT00000730

Brief Summary

This study compares three different therapies for treatment of refractory Pneumocystis carinii pneumonia (PCP) in patients with AIDS. "Refractory" means that the patient has failed to respond to at least 4 days of treatment with either of two standard therapies: (1) sulfamethoxazole/trimethoprim (SMX/TMP) or (2) pentamidine (PEN). This study compares therapy with trimetrexate (TMTX) and leucovorin (LCV) to standard therapy and standard therapy plus high-dose steroids (methylprednisolone). The purpose is to find better and safer forms of treatment for PCP in AIDS patients. There is at present no scientific information about the best treatment for an AIDS patient with PCP who is not improving while receiving the standard therapies (SMX/TMP or PEN). New drug treatments are available, including steroid therapy and TMTX, but there is no information proving that these new treatments work better than the standard therapies.

Trial Health

35
At Risk

Trial Health Score

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

Enrollment
240

participants targeted

Target at P50-P75 for phase_3

Geographic Reach
1 country

1 active site

Status
terminated

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

March 1, 1989

Completed
10.7 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 3, 2021

Status Verified

October 1, 2021

First QC Date

November 2, 1999

Last Update Submit

October 27, 2021

Conditions

Pneumonia, Pneumocystis CariniiHIV Infections

Keywords

Trimethoprim-Sulfamethoxazole CombinationTrimetrexateAIDS-Related Opportunistic InfectionsPneumonia, Pneumocystis cariniiLeucovorinFolic Acid AntagonistsAcquired Immunodeficiency SyndromeAntiprotozoal AgentsSulfamethoxazole-Trimethoprim

Interventions

Trimetrexate glucuronateDRUG
MethylprednisoloneDRUG
Pentamidine isethionateDRUG
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:
  • physiologic replacement doses of steroids.
  • Pneumocystis carinii pneumonia (PCP) in patient who is HIV positive by ELISA, HIV culture, or p24 antigenemia, or is a member of a risk group for HIV infection.
  • Failed at least 4 but not \> 14 full days' therapy with either sulfamethoxazole/trimethoprim (SMX/TMP) or parenteral pentamidine. Patients must have received therapy with only one of the two conventional agents prior to enrollment.
  • Patients in whom an unequivocal diagnosis of this episode of PCP has been or can be established by morphologic confirmation of three or more typical Pneumocystis carinii organisms in sputum, bronchoalveolar lavage fluid, or lung tissue obtained by transbronchial or open lung biopsy within 15 days prior to study entry.
  • Patients in whom no significant improvement in arterial-alveolar oxygen pressure (defined as a decrease of at least 15mm Hg) is observed in the 24 hours prior to entry.
  • Patient is willing to have maximal medical support, including pressors, invasive monitoring, and/or mechanical ventilation, during at least the first 7 days of protocol therapy if such support is necessary. Continuation of maximal medical support beyond 7 days is at discretion of investigator and patient.
  • Patients with history of hypersensitivity less severe than type I may be enrolled if, in opinion of investigator, these adverse effects do not prohibit rechallenge with the drug.
  • Prior Medication:
  • Required:
  • At least 4 full days but no greater than 14 full days of parenteral and/or oral therapy with sulfamethoxazole/trimethoprim (SMX/TMP) or pentamidine.
  • Allowed:
  • Zidovudine (AZT).

You may not qualify if:

  • Co-existing Condition:
  • Excluded:
  • Patients with history of type I hypersensitivity (urticaria, angioedema, anaphylaxis), exfoliative dermatitis, or other life-threatening reaction secondary to trimetrexate, sulfamethoxazole/trimethoprim, or pentamidine.
  • Presence of any process that, in the opinion of investigator, would be adversely and seriously affected by steroid therapy.
  • Concurrent Medication:
  • Excluded:
  • Zidovudine (AZT).
  • Myelosuppressive agents.
  • Nephrotoxic agents.
  • AZT may be resumed at completion of study.
  • Excluded:
  • Patients with history of type I hypersensitivity (urticaria, angioedema, anaphylaxis), exfoliative dermatitis, or other life-threatening reaction secondary to trimetrexate, sulfamethoxazole/trimethoprim, or pentamidine.
  • Presence of any process that, in the opinion of investigator, would be adversely and seriously affected by steroid therapy.
  • Prior Medication:
  • Excluded within 4 days of study entry:
  • +3 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Julio Arroyo

West Columbia, South Carolina, 29169, United States

Location

Related Publications (1)

  • Amsden GW, Kowalsky SF, Morse GD. Trimetrexate for Pneumocystis carinii pneumonia in patients with AIDS. Ann Pharmacother. 1992 Feb;26(2):218-26. doi: 10.1177/106002809202600217.

    PMID: 1532518BACKGROUND

MeSH Terms

Conditions

Pneumonia, PneumocystisHIV InfectionsAIDS-Related Opportunistic InfectionsAcquired Immunodeficiency Syndrome

Interventions

trimetrexate glucuronateMethylprednisolonePentamidineTrimethoprim, 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)

PrednisolonePregnadienetriolsPregnadienesPregnanesSteroidsFused-Ring CompoundsPolycyclic CompoundsBenzamidinesAmidinesOrganic ChemicalsSulfamethoxazoleBenzenesulfonamidesSulfonamidesAmidesSulfanilamidesAniline CompoundsAminesBenzene DerivativesHydrocarbons, AromaticHydrocarbons, CyclicHydrocarbonsSulfonesSulfur CompoundsTrimethoprimPyrimidinesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsDrug CombinationsPharmaceutical PreparationsFormyltetrahydrofolatesTetrahydrofolatesFolic AcidPterinsPteridinesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingCoenzymesEnzymes and Coenzymes

Study Officials

  • Masur H

    STUDY CHAIR

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Purpose
TREATMENT
Sponsor Type
NIH
Responsible Party
SPONSOR

Study Record Dates

First Submitted

November 2, 1999

First Posted

August 31, 2001

Study Completion

March 1, 1989

Last Updated

November 3, 2021

Record last verified: 2021-10

Locations

US(1)