Pneumonia, Pneumocystis CariniiPhase 3NCT00001014
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, Sulfamethoxazole-Trimethoprim and Leucovorin calcium in people with Pneumonia, Pneumocystis Carinii and HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 6 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, Sulfamethoxazole-Trimethoprim and Leucovorin calcium
- How many people
- 302 participants
- Where
- 6 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 q4h should not be prescribed as a standing order for more than 48 hours.
- Prior Medication:
- Allowed:
- Zidovudine as long as such therapy is suspended prior to randomization and not reinstituted until therapy for the acute episode is completed.
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- 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 alveolar-arterial oxygen differences = or > 30 mm Hg on room air.
Who cannot join
- Patients with the following are excluded:
- Inability to have alveolar blood gas analysis on room air.
- Medically unable to receive a liter of intravenous fluid (5 percent dextrose in water) per 24 hours. This procedure is required in order to maintain blinding.
- Prior Medication:
- Excluded within 14 days of study entry:
- Systemic steroids exceeding physiological replacement.
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- Other investigational drugs.
- Excluded within 6 weeks of study entry:
- Antiprotozoal regimen for this episode consisting of pentamidine, eflornithine, DFMO, or dapsone, for therapy of active Pneumocystis carinii pneumonia (PCP)
- 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.
- Requirement for treatment with agents that are known to be myelosuppressive or nephrotoxic during the period of acute Pneumocystis carinii pneumonia (PCP) therapy.
- Other drugs for the treatment or prevention of AIDS or Pneumocystis carinii pneumonia (PCP); disulcid; aspirin; acetaminophen q4h for more than 48 hours.
Trial locations and contacts
6 sites in 1 country.
6 sites in 1 country
United States6 sites
SUNY - Buffalo, Erie County Medical Ctr.
Buffalo, New York, 14215
Rush Univ. Med. Ctr. ACTG CRS
Chicago, Illinois, 60611
Case CRS
Cleveland, Ohio, 44106
Tulane Med. Ctr. - Charity Hosp. of New Orleans, ACTU
New Orleans, Louisiana, 70112
Ucsf Aids Crs
San Francisco, California, 94110
Washington U CRS
St Louis, Missouri
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. 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 in treating PCP and in preventing a recurrence of PCP.
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 in treating PCP and in preventing a recurrence of PCP.
Patients entered in the study are randomly assigned to trimetrexate / leucovorin (TMTX / LCV) or to sulfamethoxazole/trimethoprim (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 pentamidine 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. Drug therapy aimed at preventing recurrence of PCP is not allowed for a minimum of 4 weeks after the completion of study therapy.
- Conditions
- Pneumonia, Pneumocystis Carinii, HIV Infections
- Being tested
- Trimetrexate glucuronate, Sulfamethoxazole-Trimethoprim, Leucovorin calcium
- Keywords
- Trimethoprim-Sulfamethoxazole Combination, Trimetrexate, AIDS-Related Opportunistic Infections, Pneumonia, Pneumocystis carinii, Infusions, Intravenous, Leucovorin, Drug Therapy, Combination, Administration, Oral, 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
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
- 302 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
- NCT00001014
- Sponsor's protocol ID
- ACTG 031
- Other IDs
- 11007
- 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
- NCT00001014
- Acronym / sponsor ID
- ACTG 031
- Conditions
- Pneumonia, Pneumocystis Carinii, HIV Infections
- Keywords
- Trimethoprim-Sulfamethoxazole Combination, Trimetrexate, AIDS-Related Opportunistic Infections, Pneumonia, Pneumocystis carinii, Infusions, Intravenous, Leucovorin, Drug Therapy, Combination, Administration, Oral
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 302 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. 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 in treating PCP and in preventing a recurrence of PCP.
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 in treating PCP and in preventing a recurrence of PCP.
Patients entered in the study are randomly assigned to trimetrexate / leucovorin (TMTX / LCV) or to sulfamethoxazole/trimethoprim (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 pentamidine 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. Drug therapy aimed at preventing recurrence of PCP is not allowed for a minimum of 4 weeks after the completion of study therapy.
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 (9 listed)
- Acetaminophen 650 mg prescribed as necessary for temperature > 38.7 degrees C. Acetaminophen q4h should not be prescribed as a standing order for more than 48 hours.
- Zidovudine as long as such therapy is suspended prior to randomization and not reinstituted until therapy for the acute episode is completed.
- 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 alveolar-arterial oxygen differences = or > 30 mm Hg on room air.
Key exclusion criteria (13 listed)
- Inability to have alveolar blood gas analysis on room air.
- Medically unable to receive a liter of intravenous fluid (5 percent dextrose in water) per 24 hours. This procedure is required in order to maintain blinding.
- Systemic steroids exceeding physiological replacement.
- Other investigational drugs.
- Excluded within 6 weeks of study entry:
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 | – |
| 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
6 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, Sulfamethoxazole-Trimethoprim and Leucovorin calcium in people with Pneumonia, Pneumocystis Carinii and HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 6 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 9 inclusion and 13 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 6 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 NCT00001014, 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.