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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00001013
Recruitment Status : Completed
First Posted : August 31, 2001
Last Update Posted : March 19, 2012
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)

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.

Condition or disease Intervention/treatment Phase
Pneumonia, Pneumocystis Carinii HIV Infections Drug: Trimetrexate glucuronate Drug: Pentamidine isethionate Drug: Sulfamethoxazole-Trimethoprim Drug: Leucovorin calcium Phase 3

Detailed Description:

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.

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Study Type : Interventional  (Clinical Trial)
Enrollment : 364 participants
Intervention Model: Parallel Assignment
Primary Purpose: Treatment
Official Title: A Randomized, Comparative, Double-Blind Trial of Trimetrexate (CI-898) With Leucovorin Calcium Rescue Versus Trimethoprim / Sulfamethoxazole for Moderately Severe Pneumocystis Carinii Pneumonia in Patients With AIDS
Actual Study Completion Date : September 1991

Information from the National Library of Medicine

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Ages Eligible for Study:   12 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria

Concurrent Medication:


  • 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:


  • 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:


  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00001013

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Sponsors and Collaborators
National Institute of Allergy and Infectious Diseases (NIAID)
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Study Chair: Sattler FR
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Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID) Identifier: NCT00001013    
Other Study ID Numbers: ACTG 029
11005 ( Registry Identifier: DAIDS ES Registry Number )
First Posted: August 31, 2001    Key Record Dates
Last Update Posted: March 19, 2012
Last Verified: March 2012
Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Trimethoprim-Sulfamethoxazole Combination
AIDS-Related Opportunistic Infections
Pneumonia, Pneumocystis carinii
Infusions, Intravenous
Drug Therapy, Combination
Folic Acid Antagonists
Acquired Immunodeficiency Syndrome
Antiprotozoal Agents
AIDS-Related Complex
Additional relevant MeSH terms:
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Pneumonia, Pneumocystis
Lung Diseases
Respiratory Tract Diseases
Respiratory Tract Infections
Lung Diseases, Fungal
Pneumocystis Infections
Trimethoprim, Sulfamethoxazole Drug Combination
Calcium-Regulating Hormones and Agents
Physiological Effects of Drugs
Protective Agents
Vitamin B Complex
Growth Substances
Anti-Infective Agents, Urinary
Anti-Infective Agents
Renal Agents
Antiprotozoal Agents