Pneumonia, Pneumocystis CariniiPhase 3NCT00000730
Comparison of Three Treatments for Pneumocystis Pneumonia in AIDS Patients
A Phase 3 study testing Trimetrexate glucuronate, Methylprednisolone and Pentamidine isethionate 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
This study compares three different therapies for treatment of refractory Pneumocystis carinii pneumonia (PCP) in patients with AIDS. "Refractory" means that the patient has failed to respond to at least 4 days of treatment with either of two standard therapies: (1) sulfamethoxazole/trimethoprim (SMX/TMP) or (2)… 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, Methylprednisolone and Pentamidine isethionate
- How many people
- 240 participants
- Where
- 1 siteUnited States
- Study dates
- Start not givento Mar 1989
- 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:
- physiologic replacement doses of steroids.
- Pneumocystis carinii pneumonia (PCP) in patient who is HIV positive by ELISA, HIV culture, or p24 antigenemia, or is a member of a risk group for HIV infection.
- Failed at least 4 but not > 14 full days' therapy with either sulfamethoxazole/trimethoprim (SMX/TMP) or parenteral pentamidine. Patients must have received therapy with only one of the two conventional agents prior to enrollment.
- Patients in whom an unequivocal diagnosis of this episode of PCP has been or can be established by morphologic confirmation of three or more typical Pneumocystis carinii organisms in sputum, bronchoalveolar lavage fluid, or lung tissue obtained by transbronchial or open lung biopsy within 15 days prior to study entry.
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- Patients in whom no significant improvement in arterial-alveolar oxygen pressure (defined as a decrease of at least 15mm Hg) is observed in the 24 hours prior to entry.
- Patient is willing to have maximal medical support, including pressors, invasive monitoring, and/or mechanical ventilation, during at least the first 7 days of protocol therapy if such support is necessary. Continuation of maximal medical support beyond 7 days is at discretion of investigator and patient.
- Patients with history of hypersensitivity less severe than type I may be enrolled if, in opinion of investigator, these adverse effects do not prohibit rechallenge with the drug.
- Prior Medication:
- Required:
- At least 4 full days but no greater than 14 full days of parenteral and/or oral therapy with sulfamethoxazole/trimethoprim (SMX/TMP) or pentamidine.
- Allowed:
- Zidovudine (AZT).
Who cannot join
- Co-existing Condition:
- Excluded:
- Patients with history of type I hypersensitivity (urticaria, angioedema, anaphylaxis), exfoliative dermatitis, or other life-threatening reaction secondary to trimetrexate, sulfamethoxazole/trimethoprim, or pentamidine.
- Presence of any process that, in the opinion of investigator, would be adversely and seriously affected by steroid therapy.
- Failure to meet inclusion criteria.
- Concurrent Medication:
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- Excluded:
- Zidovudine (AZT).
- Myelosuppressive agents.
- Nephrotoxic agents.
- AZT may be resumed at completion of study.
- Excluded:
- Patients with history of type I hypersensitivity (urticaria, angioedema, anaphylaxis), exfoliative dermatitis, or other life-threatening reaction secondary to trimetrexate, sulfamethoxazole/trimethoprim, or pentamidine.
- Presence of any process that, in the opinion of investigator, would be adversely and seriously affected by steroid therapy.
- Failure to meet inclusion criteria.
- Prior Medication:
- Excluded within 4 days of study entry:
- Any other investigational agent.
- Excluded within 14 days of study entry:
- Steroids (other than physiologic replacement doses).
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Randomized, Comparative Trial of Trimetrexate With Leucovorin Rescue Versus Standard Anti-Pneumocystis Therapy Versus Standard Anti-Pneumocystis Therapy With High Dose Steroids for AIDS Patients With Pneumocystis Pneumonia Who Appear to Be Refractory to Conventional Drugs
This study compares three different therapies for treatment of refractory Pneumocystis carinii pneumonia (PCP) in patients with AIDS. "Refractory" means that the patient has failed to respond to at least 4 days of treatment with either of two standard therapies: (1) sulfamethoxazole/trimethoprim (SMX/TMP) or (2) pentamidine (PEN). This study compares therapy with trimetrexate (TMTX) and leucovorin (LCV) to standard therapy and standard therapy plus high-dose steroids (methylprednisolone). The purpose is to find better and safer forms of treatment for PCP in AIDS patients. There is at present no scientific information about the best treatment for an AIDS patient with PCP who is not improving while receiving the standard therapies (SMX/TMP or PEN). New drug treatments are available, including steroid therapy and TMTX, but there is no information proving that these new treatments work better than the standard therapies.
Read the detailed description
There is at present no scientific information about the best treatment for an AIDS patient with PCP who is not improving while receiving the standard therapies (SMX/TMP or PEN). New drug treatments are available, including steroid therapy and TMTX, but there is no information proving that these new treatments work better than the standard therapies.
Hospitalized patients who have failed to respond to at least 4 full days but no greater than 14 full days of therapy with SMX/TMP or PEN are randomly placed into one of three study groups. Patients are stratified for (1) mechanical ventilation at enrollment, (2) prior zidovudine therapy of at least 4 weeks duration, and (3) first versus subsequent episode of PCP. One group of patients receives TMTX by intravenous infusion for 21 days and LCV for 24 days. The second and third group of patients receive either PEN or SMX/TMP depending on which therapy they have already received and not improved on. The difference between the second and third group is that the second group receives the conventional therapy (PEN or SMX/TMP) and a placebo (inactive medication) and the third group receives the conventional therapy and prednisolone. Neither investigators nor patients know whether patients receive methylprednisolone. Patients continue study treatment until a study end point is reached or for a minimum of 21 days (unless there is toxicity).
- Conditions
- Pneumonia, Pneumocystis Carinii, HIV Infections
- Being tested
- Trimetrexate glucuronate, Methylprednisolone, Pentamidine isethionate, Sulfamethoxazole-Trimethoprim, Leucovorin calcium
- Keywords
- Trimethoprim-Sulfamethoxazole Combination, Trimetrexate, AIDS-Related Opportunistic Infections, Pneumonia, Pneumocystis carinii, Leucovorin, Folic Acid Antagonists, Acquired Immunodeficiency Syndrome, Antiprotozoal Agents, Sulfamethoxazole-Trimethoprim
- Medical subject headings
- Pneumonia, Pneumocystis, HIV Infections, AIDS-Related Opportunistic Infections, Acquired Immunodeficiency Syndrome
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 completionMar 1989
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
- Allocation
- Randomised
- Enrolment
- 240 participants
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Masur H, Study chair
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00000730
- Sponsor's protocol ID
- ACTG 030
- Other IDs
- 11006
- Status last verified
- Oct 2021
- First submitted
- 2 Nov 1999
- Last updated
- 3 Nov 2021
- Results posted
- No
Publications
Amsden GW, Kowalsky SF, Morse GD. Trimetrexate for Pneumocystis carinii pneumonia in patients with AIDS. Ann Pharmacother. 1992 Feb;26(2):218-26. doi: 10.1177/106002809202600217.
PubMed 1532518
Study at a glance
From the registry record, last updated by the sponsor on 3 Nov 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Comparative Trial of Trimetrexate With Leucovorin Rescue Versus Standard Anti-Pneumocystis Therapy Versus Standard Anti-Pneumocystis Therapy With High Dose Steroids for AIDS Patients With Pneumocystis Pneumonia Who Appear to Be Refractory to Conventional Drugs
- ClinicalTrials.gov ID
- NCT00000730
- Acronym / sponsor ID
- ACTG 030
- Conditions
- Pneumonia, Pneumocystis Carinii, HIV Infections
- Keywords
- Trimethoprim-Sulfamethoxazole Combination, Trimetrexate, AIDS-Related Opportunistic Infections, Pneumonia, Pneumocystis carinii, Leucovorin, Folic Acid Antagonists, Acquired Immunodeficiency Syndrome, Antiprotozoal Agents
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 240 participants
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Study completion
- Mar 1989 (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.
This study compares three different therapies for treatment of refractory Pneumocystis carinii pneumonia (PCP) in patients with AIDS. "Refractory" means that the patient has failed to respond to at least 4 days of treatment with either of two standard therapies: (1) sulfamethoxazole/trimethoprim (SMX/TMP) or (2) pentamidine (PEN). This study compares therapy with trimetrexate (TMTX) and leucovorin (LCV) to standard therapy and standard therapy plus high-dose steroids (methylprednisolone). The purpose is to find better and safer forms of treatment for PCP in AIDS patients. There is at present no scientific information about the best treatment for an AIDS patient with PCP who is not improving while receiving the standard therapies (SMX/TMP or PEN). New drug treatments are available, including steroid therapy and TMTX, but there is no information proving that these new treatments work better than the standard therapies.
Detailed description
There is at present no scientific information about the best treatment for an AIDS patient with PCP who is not improving while receiving the standard therapies (SMX/TMP or PEN). New drug treatments are available, including steroid therapy and TMTX, but there is no information proving that these new treatments work better than the standard therapies.
Hospitalized patients who have failed to respond to at least 4 full days but no greater than 14 full days of therapy with SMX/TMP or PEN are randomly placed into one of three study groups. Patients are stratified for (1) mechanical ventilation at enrollment, (2) prior zidovudine therapy of at least 4 weeks duration, and (3) first versus subsequent episode of PCP. One group of patients receives TMTX by intravenous infusion for 21 days and LCV for 24 days. The second and third group of patients receive either PEN or SMX/TMP depending on which therapy they have already received and not improved on. The difference between the second and third group is that the second group receives the conventional therapy (PEN or SMX/TMP) and a placebo (inactive medication) and the third group receives the conventional therapy and prednisolone. Neither investigators nor patients know whether patients receive methylprednisolone. Patients continue study treatment until a study end point is reached or for a minimum of 21 days (unless there is toxicity).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
Who may qualify
- Ages
- 12 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (14 listed)
- physiologic replacement doses of steroids.
- Pneumocystis carinii pneumonia (PCP) in patient who is HIV positive by ELISA, HIV culture, or p24 antigenemia, or is a member of a risk group for HIV infection.
- Failed at least 4 but not > 14 full days' therapy with either sulfamethoxazole/trimethoprim (SMX/TMP) or parenteral pentamidine. Patients must have received therapy with only one of the two conventional agents prior to enrollment.
- Patients in whom an unequivocal diagnosis of this episode of PCP has been or can be established by morphologic confirmation of three or more typical Pneumocystis carinii organisms in sputum, bronchoalveolar lavage fluid, or lung tissue obtained by transbronchial or open lung biopsy within 15 days prior to study entry.
- Patients in whom no significant improvement in arterial-alveolar oxygen pressure (defined as a decrease of at least 15mm Hg) is observed in the 24 hours prior to entry.
Key exclusion criteria (20 listed)
- Patients with history of type I hypersensitivity (urticaria, angioedema, anaphylaxis), exfoliative dermatitis, or other life-threatening reaction secondary to trimetrexate, sulfamethoxazole/trimethoprim, or pentamidine.
- Presence of any process that, in the opinion of investigator, would be adversely and seriously affected by steroid therapy.
- Failure to meet inclusion criteria.
- Zidovudine (AZT).
- Myelosuppressive agents.
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 | – |
| Methylprednisolone | Drug | – |
| Pentamidine isethionate | Drug | – |
| Sulfamethoxazole-Trimethoprim | Drug | – |
| Leucovorin calcium | Drug | – |
Primary outcome
Not reported in the source record.
Results and safety
The study was stopped early. Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Nov 2021.
- Background: PubMed 1532518Amsden GW, Kowalsky SF, Morse GD. Trimetrexate for Pneumocystis carinii pneumonia in patients with AIDS. Ann Pharmacother. 1992 Feb;26(2):218-26. doi: 10.1177/106002809202600217.
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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.
Masur H 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, Methylprednisolone and Pentamidine isethionate 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 14 inclusion and 20 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: stopped early, as of the sponsor's last update on 3 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 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 was stopped early. Results are not available in the source record.
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 NCT00000730, 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 3 Nov 2021.