Search / Trial NCT00000724

A Study of Trimetrexate With Leucovorin Rescue for AIDS Patients Who Are Refractory to Standard Therapies for Pneumocystis Carinii Pneumonia

Launched by NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES (NIAID) · Aug 30, 2001

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Trial Information

Current as of February 21, 2024

Completed

Keywords

Trimetrexate Pneumonia, Pneumocystis Carinii Injections, Intravenous Leucovorin Drug Evaluation Drug Therapy, Combination Folic Acid Antagonists Acquired Immunodeficiency Syndrome Antiprotozoal Agents

Description

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. AMENDED: 08/01/90. As of August 31, 1989, 437 patients were enrolled into uncontrolled studies of trimetrexate for PCP: 214 in TX...

Gender

All

Eligibility criteria

  • Inclusion Criteria
  • 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.
  • Transaminase > 5 x ULN or = or > 300 IU if baseline abnormal.
  • Daily temperature = or > 103 degrees F beginning after the 5th day of treatment and persisting for at least 3 days and not responsive to antipyretic therapy, with no other discernible cause.
  • Any other severe or life-threatening adverse reaction to TMP / SMX that, in the investigator's opinion, makes continued or recurrent treatment with TMP / SMX inadvisable (approved on a case-by-case basis by the NIAID clinical monitor).
  • Intolerance to pentamidine is defined as one or more of the following:
  • Platelets < 50000 platelets/mm3 or absolute neutrophil count (polys + bands) < 550 cells/mm3 on at least two occasions = or > 12 hours apart.
  • Serum creatinine > 3.0 mg/dl.
  • Systolic blood pressure < 90 mm requiring supportive therapy.
  • Symptomatic hypoglycemia with blood glucose = or < 40 or hyperglycemia requiring therapy.
  • Pancreatitis with laboratory confirmation (abnormal amylase and/or lipase).
  • Any other severe or life-threatening adverse reaction to pentamidine that, in the investigator's opinion, makes continued or recurrent treatment with pentamidine inadvisable (approved on a case-by-case basis by the NIAID clinical monitor).
  • Exclusion Criteria
  • 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.

Attachments

readout_NCT00000724_2024-02-21.pdf

4.5 MB

NCT00000724_study_protocol.pdf

4.5 MB

About company

The National Institute of Allergy and Infectious Diseases (NIAID, /ˈnaɪ.æd/) is one of the 27 institutes and centers that make up the National Institutes of Health (NIH), an agency of the United States Department of Health and Human Services (HHS). NIAID's mission is to conduct basic and applied research to better understand, treat, and prevent infectious, immunologic, and allergic diseases.

Contacts

JC

Jennifer Cobb

Immunology at National Institute of Allergy and Infectious Diseases (NIAID)

Locations

Morris Plains, New Jersey, United States

People applied

Timeline

First submit

Trial launched

Trial updated

Estimated completion

Not reported

Reviews (48)

4.6

All reviews come from applied patients

5 stars
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6
3 stars
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Leslie Alexander
20 September 2023

Duis aute irure dolor in reprehenderit in voluptate velit esse cillum dolore eu fugiat nulla pariatur. Excepteur sint occaecat cupidatat non proident, sunt in culpa qui officia deserunt mollit anim id est laborum?

Michael Foster
20 September 2023

Duis aute irure dolor in reprehenderit in voluptate velit esse cillum dolore eu fugiat nulla pariatur. Excepteur sint occaecat cupidatat non proident, sunt in culpa qui officia deserunt mollit anim id est laborum?

Dries Vincent
20 September 2023

Duis aute irure dolor in reprehenderit in voluptate velit esse cillum dolore eu fugiat nulla pariatur. Excepteur sint occaecat cupidatat non proident, sunt in culpa qui officia deserunt mollit anim id est laborum?

Leslie Alexander
20 September 2023

Duis aute irure dolor in reprehenderit in voluptate velit esse cillum dolore eu fugiat nulla pariatur. Excepteur sint occaecat cupidatat non proident, sunt in culpa qui officia deserunt mollit anim id est laborum?

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