Pneumonia, Pneumocystis CariniiPhase 3NCT00001013
Comparison of Trimetrexate Plus Leucovorin Calcium Rescue Versus Sulfamethoxazole-Trimethoprim in the Treatment of Pneumocystis Carinii Pneumonia (PCP) in Patients With AIDS
A Phase 3 study testing Trimetrexate glucuronate, Pentamidine isethionate and Sulfamethoxazole-Trimethoprim in people with Pneumonia, Pneumocystis Carinii and HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 23 sites in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 12 years and older
- Conditions the study is for
- Pneumonia, Pneumocystis Carinii, HIV Infections
- What is being tested?
- Trimetrexate glucuronate, Pentamidine isethionate and Sulfamethoxazole-Trimethoprim
- How many people
- 364 participants
- Where
- 23 sitesUnited States
- Study dates
- Start not givento Sep 1991
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Concurrent Medication:
- Allowed:
- 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:
- Allowed:
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- 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.
Who cannot join
- 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:
- Excluded:
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- 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.
Trial locations and contacts
23 sites in 1 country.
23 sites in 1 country
United States23 sites
SUNY / Erie County Med Ctr at Buffalo
Buffalo, New York, 14215
Northwestern Univ Med School
Chicago, Illinois, 60611
Holmes Hosp / Univ of Cincinnati Med Ctr
Cincinnati, Ohio, 452670405
Univ Hosp of Cleveland / Case Western Reserve Univ
Cleveland, Ohio, 44106
City Hosp Ctr at Elmhurst / Mount Sinai Hosp
Elmhurst, New York, 11373
Milton S Hershey Med Ctr
Hershey, Pennsylvania, 170330850
Los Angeles County - USC Med Ctr
Los Angeles, California, 90033
Univ of Miami School of Medicine
Miami, Florida, 331361013
Charity Hosp / Tulane Univ Med School
New Orleans, Louisiana, 70112
Louisiana State Univ Med Ctr / Tulane Med School
New Orleans, Louisiana, 70112
Tulane Univ School of Medicine
New Orleans, Louisiana, 70112
Beth Israel Med Ctr / Peter Krueger Clinic
New York, New York, 10003
Mount Sinai Med Ctr
New York, New York, 10029
Thomas Jefferson Med College
Philadelphia, Pennsylvania, 19107
Univ of Rochester Medical Center
Rochester, New York, 14642
SUNY - Stony Brook
Stony Brook, New York, 117948153
SUNY / State Univ of New York
Syracuse, New York, 13210
Bronx Municipal Hosp Ctr/Jacobi Med Ctr
The Bronx, New York, 10461
Jack Weiler Hosp / Bronx Municipal Hosp
The Bronx, New York, 10465
Montefiore Med Ctr / Bronx Municipal Hosp
The Bronx, New York, 10467
George Washington Univ Med Ctr
Washington D.C., District of Columbia, 20037
Julio Arroyo
West Columbia, South Carolina, 29169
Univ of Massachusetts Med Ctr
Worcester, Massachusetts, 01655
About this study
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
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.
Read the 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.
- Conditions
- Pneumonia, Pneumocystis Carinii, HIV Infections
- Being tested
- Trimetrexate glucuronate, Pentamidine isethionate, Sulfamethoxazole-Trimethoprim, Leucovorin calcium
- Keywords
- Trimethoprim-Sulfamethoxazole Combination, Trimetrexate, AIDS-Related Opportunistic Infections, Pneumonia, Pneumocystis carinii, Pentamidine, Infusions, Intravenous, Leucovorin, Drug Therapy, Combination, Folic Acid Antagonists, Aerosols, Acquired Immunodeficiency Syndrome, Antiprotozoal Agents, AIDS-Related Complex, Sulfamethoxazole-Trimethoprim
- Medical subject headings
- Pneumonia, Pneumocystis, HIV Infections, AIDS-Related Opportunistic Infections, Acquired Immunodeficiency Syndrome, AIDS-Related Complex
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Trimetrexate glucuronateDrug
Pentamidine isethionateDrug
Sulfamethoxazole-TrimethoprimDrug
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Aug 2001 (estimated)
- Study completionSep 1991
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Pneumonia, Pneumocystis CariniiStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Intervention model
- Parallel groups
- Enrolment
- 364 participants
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Sattler FR, Study chair
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00001013
- Sponsor's protocol ID
- ACTG 029
- Other IDs
- 11005
- Status last verified
- Oct 2021
- First submitted
- 2 Nov 1999
- Last updated
- 4 Nov 2021
- Results posted
- No
Publications
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.
PubMed 8014493
Study at a glance
From the registry record, last updated by the sponsor on 4 Nov 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00001013
- Acronym / sponsor ID
- ACTG 029
- Conditions
- Pneumonia, Pneumocystis Carinii, HIV Infections
- Keywords
- Trimethoprim-Sulfamethoxazole Combination, Trimetrexate, AIDS-Related Opportunistic Infections, Pneumonia, Pneumocystis carinii, Pentamidine, Infusions, Intravenous, Leucovorin, Drug Therapy, Combination
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 364 participants
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Study completion
- Sep 1991 (actual)
- First posted
- 31 Aug 2001 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Treatment
- Intervention model
- Parallel groups
Who may qualify
- Ages
- 12 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (10 listed)
- 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.
- 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).
Key exclusion criteria (18 listed)
- 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.
- Other drugs for the treatment or prevention of AIDS or Pneumocystis carinii pneumonia (PCP).
- Disalcid.
- Aspirin.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Trimetrexate glucuronate | Drug | – |
| Pentamidine isethionate | Drug | – |
| Sulfamethoxazole-Trimethoprim | Drug | – |
| Leucovorin calcium | Drug | – |
Primary outcome
Not reported in the source record.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Nov 2021.
- Background: PubMed 8014493Sattler 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Sattler FR study chair
23 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Trimetrexate glucuronate, Pentamidine isethionate and Sulfamethoxazole-Trimethoprim in people with Pneumonia, Pneumocystis Carinii and HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 23 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Nov 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 23 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00001013, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Nov 2021.