Pneumonia, Pneumocystis CariniiPhase 3NCT00001016
A Treatment Protocol for the Use of Trimetrexate With Leucovorin Rescue for AIDS Patients With Pneumocystis Carinii Pneumonia and Serious Intolerance to Approved Therapies
A Phase 3 study testing Trimetrexate glucuronate and Leucovorin calcium in people with Pneumonia, Pneumocystis Carinii and HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.
Trial summary
To determine the safety and effectiveness of an investigational drug trimetrexate (TMTX) with leucovorin rescue (LCV) in the treatment of Pneumocystis carinii pneumonia (PCP) in patients who have AIDS, are HIV positive, or are at high risk for HIV infection, and who have demonstrated serious adverse effects from the… 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 and Leucovorin calcium
- How many people
- Not given
- Where
- 1 siteUnited States
- Study dates
- Start not givento Aug 2007
- 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:
- Blood pressure medication.
- Concurrent Treatment:
- Allowed:
- Blood products.
Show all 19Show fewer
- Ventilatory support.
- Patients must have the following:
- Diagnosis of Pneumocystis carinii pneumonia (PCP).
- Be HIV positive by ELISA, HIV culture, or p24 antigenemia; or be a member of an identified risk group.
- Intolerant to trimethoprim / sulfamethoxazole (TMP / SMX).
- Intolerant to pentamidine.
- Prior Medication:
- Allowed:
- Trimethoprim / sulfamethoxazole trials.
- Pentamidine trials.
- Myelosuppressive agents.
- Nephrotoxic agents.
- Zidovudine (AZT).
Who cannot join
- Co-existing Condition:
- Patients who do not meet the inclusion criteria are excluded.
- Concurrent Medication:
- Excluded:
- Myelosuppressive agents.
- Nephrotoxic agents.
- Other investigational drugs including high-dose steroids (exceeding physiologic replacement doses).
- Patients who do not meet the inclusion criteria are excluded.
Trial locations and contacts
1 site in 1 country.
United States1 site
Warner-Lambert Parke-Davis
Morris Plains, New Jersey, 07950
About this study
To determine the safety and effectiveness of an investigational drug trimetrexate (TMTX) with leucovorin rescue (LCV) in the treatment of Pneumocystis carinii pneumonia (PCP) in patients who have AIDS, are HIV positive, or are at high risk for HIV infection, and who have demonstrated serious adverse effects from the conventional therapies for PCP.
The drugs usually used to treat PCP in AIDS patients (trimethoprim / sulfamethoxazole and pentamidine) have had to be discontinued in many patients because of severe adverse effects. Currently there are no proven alternatives to these drugs. TMTX was chosen for this trial because it has been found to be very active against the PCP organism in laboratory tests. In a preliminary trial, TMTX in combination with LCV has been effective against PCP with fewer and less severe adverse effects.
Read the detailed description
The drugs usually used to treat PCP in AIDS patients (trimethoprim / sulfamethoxazole and pentamidine) have had to be discontinued in many patients because of severe adverse effects. Currently there are no proven alternatives to these drugs. TMTX was chosen for this trial because it has been found to be very active against the PCP organism in laboratory tests. In a preliminary trial, TMTX in combination with LCV has been effective against PCP with fewer and less severe adverse effects.
AMENDED: 08/01/90. As of August 31, 1989, 437 patients were enrolled into uncontrolled studies of trimetrexate for PCP:214 in TX 301/ACTG 0=039 (trimetrexate for patients intolerant of approved therapies) and 223 in NS 401 (trimetrexate for patients refractory to approved therapies). The analysis of overall response rate, stringently defined as having received at least 14 days of trimetrexate and being alive at follow-up 1 month after the completion of therapy, reveals 84/159 intolerant patients and 48/160 refractory patients had responded, for rates of 53 percent and 30 percent, respectively. These response rates include all individuals who received at least one dose of trimetrexate. Of the 111 patients who were ventilator-dependent at study entry, 18 completed a course of therapy and were alive a month later, for a response rate of 16 percent. All other ventilated patients died. The most common severe (grades 3 and 4) toxicities were: transaminase elevation (greater than 5 x normal) in 94 patients, anemia (less than 7.9 g/dl) in 109, neutropenia (less than 750 cells/mm3) in 58, fever (greater than 40 degrees C) in 37, and thrombocytopenia (less than 50,000 platelets/mm3) in 27.
Toxicity required discontinuation of therapy in approximately 5 percent of all patients. Original design: Patients entered in the study are given TMTX once a day for 21 days and LCV 4 times a day (every 6 hours) for 24 days. Doses are determined by body size. Both drugs are given by intravenous infusion, but LCV may be given orally after the first 10 days. Doses are adjusted if side effects, such as low white blood cell counts, 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 administration of TMTX and LCV has been completed. After treatment with TMTX, the patient may be treated with other drugs to prevent the recurrence of PCP at the discretion of his/her physician.
- Conditions
- Pneumonia, Pneumocystis Carinii, HIV Infections
- Being tested
- Trimetrexate glucuronate, Leucovorin calcium
- Keywords
- Trimetrexate, Pneumonia, Pneumocystis carinii, Quinazolines, Infusions, Intravenous, Injections, Intravenous, Leucovorin, Drug Evaluation, Drug Therapy, Combination, Administration, Oral, Acquired Immunodeficiency Syndrome, Antiprotozoal Agents, AIDS-Related Complex
- Medical subject headings
- Pneumonia, Pneumocystis, HIV 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
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 completionAug 2007
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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
- Masking
- None (open label)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Investigators
- Feinberg J, Study chair
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00001016
- Sponsor's protocol ID
- TX 301
- Status last verified
- Jul 1993
- First submitted
- 2 Nov 1999
- Last updated
- 30 Sep 2008
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 Sep 2008. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Treatment Protocol for the Use of Trimetrexate With Leucovorin Rescue for AIDS Patients With Pneumocystis Carinii Pneumonia and Serious Intolerance to Approved Therapies
- ClinicalTrials.gov ID
- NCT00001016
- Acronym / sponsor ID
- TX 301
- Conditions
- Pneumonia, Pneumocystis Carinii, HIV Infections
- Keywords
- Trimetrexate, Pneumonia, Pneumocystis carinii, Quinazolines, Infusions, Intravenous, Injections, Intravenous, Leucovorin, Drug Evaluation, Drug Therapy, Combination
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Study completion
- Aug 2007 (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 determine the safety and effectiveness of an investigational drug trimetrexate (TMTX) with leucovorin rescue (LCV) in the treatment of Pneumocystis carinii pneumonia (PCP) in patients who have AIDS, are HIV positive, or are at high risk for HIV infection, and who have demonstrated serious adverse effects from the conventional therapies for PCP.
The drugs usually used to treat PCP in AIDS patients (trimethoprim / sulfamethoxazole and pentamidine) have had to be discontinued in many patients because of severe adverse effects. Currently there are no proven alternatives to these drugs. TMTX was chosen for this trial because it has been found to be very active against the PCP organism in laboratory tests. In a preliminary trial, TMTX in combination with LCV has been effective against PCP with fewer and less severe adverse effects.
Detailed description
The drugs usually used to treat PCP in AIDS patients (trimethoprim / sulfamethoxazole and pentamidine) have had to be discontinued in many patients because of severe adverse effects. Currently there are no proven alternatives to these drugs. TMTX was chosen for this trial because it has been found to be very active against the PCP organism in laboratory tests. In a preliminary trial, TMTX in combination with LCV has been effective against PCP with fewer and less severe adverse effects.
AMENDED: 08/01/90. As of August 31, 1989, 437 patients were enrolled into uncontrolled studies of trimetrexate for PCP:214 in TX 301/ACTG 0=039 (trimetrexate for patients intolerant of approved therapies) and 223 in NS 401 (trimetrexate for patients refractory to approved therapies). The analysis of overall response rate, stringently defined as having received at least 14 days of trimetrexate and being alive at follow-up 1 month after the completion of therapy, reveals 84/159 intolerant patients and 48/160 refractory patients had responded, for rates of 53 percent and 30 percent, respectively. These response rates include all individuals who received at least one dose of trimetrexate. Of the 111 patients who were ventilator-dependent at study entry, 18 completed a course of therapy and were alive a month later, for a response rate of 16 percent. All other ventilated patients died. The most common severe (grades 3 and 4) toxicities were: transaminase elevation (greater than 5 x normal) in 94 patients, anemia (less than 7.9 g/dl) in 109, neutropenia (less than 750 cells/mm3) in 58, fever (greater than 40 degrees C) in 37, and thrombocytopenia (less than 50,000 platelets/mm3) in 27.
Toxicity required discontinuation of therapy in approximately 5 percent of all patients. Original design: Patients entered in the study are given TMTX once a day for 21 days and LCV 4 times a day (every 6 hours) for 24 days. Doses are determined by body size. Both drugs are given by intravenous infusion, but LCV may be given orally after the first 10 days. Doses are adjusted if side effects, such as low white blood cell counts, 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 administration of TMTX and LCV has been completed. After treatment with TMTX, the patient may be treated with other drugs to prevent the recurrence of PCP at the discretion of his/her physician.
Study design
- Primary purpose
- Treatment
- Masking
- None (open label)
Who may qualify
- Ages
- 12 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (19 listed)
- Blood pressure medication.
- Blood products.
- Ventilatory support.
- Diagnosis of Pneumocystis carinii pneumonia (PCP).
- Be HIV positive by ELISA, HIV culture, or p24 antigenemia; or be a member of an identified risk group.
Key exclusion criteria (8 listed)
- Patients who do not meet the inclusion criteria are excluded.
- Myelosuppressive agents.
- Nephrotoxic agents.
- Other investigational drugs including high-dose steroids (exceeding physiologic replacement doses).
- Patients who do not meet the inclusion criteria are excluded.
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 | – |
| 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 30 Sep 2008.
Related trials for Pneumonia, Pneumocystis Carinii
RecruitingPhase 3
Low Dose Trimethoprim-Sulfamethoxazole for the Treatment of Pneumocystis Jirovecii Pneumonia
Pneumocystis, Pneumocystis Pneumonia
Not yet recruitingPhase 4
Positioning Second-line Therapies for Pneumocystis Jirovecii Pneumonia (PCP Alternatives)
Pneumocystis, Pneumocystis Infection
Not yet recruitingPhase 4
How Long Should we Give Steroids for Patients With Severe PCP
Pneumocystis Pneumonia, Pneumocystis
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.
Feinberg J study chair
1 site 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 and Leucovorin calcium in people with Pneumonia, Pneumocystis Carinii and HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site 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 19 inclusion and 8 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 30 Sep 2008. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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?
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 30 Sep 2008.