Comparison of Three Treatments for Pneumocystis Pneumonia in AIDS Patients
Information source: National Institute of Allergy and Infectious Diseases (NIAID)
Information obtained from ClinicalTrials.gov on June 20, 2008
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Pneumonia, Pneumocystis Carinii; HIV Infections
Intervention: Trimetrexate glucuronate (Drug); Methylprednisolone (Drug); Pentamidine isethionate (Drug); Sulfamethoxazole-Trimethoprim (Drug); Leucovorin calcium (Drug)
Phase: Phase 3
Status: Terminated
Sponsored by: National Institute of Allergy and Infectious Diseases (NIAID) Official(s) and/or principal investigator(s):
Masur H, Study Chair
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) 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.
Clinical Details
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
Study design: Treatment, Randomized
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).
Eligibility
Minimum age: 12 Years.
Maximum age: N/A.
Gender(s): Both.
Criteria:
Inclusion Criteria
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.
- 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).
Exclusion Criteria
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:
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).
Locations and Contacts
Julio Arroyo, West Columbia, South Carolina 29169, United States
Additional Information
Click here for more information about Pentamidine isethionate Click here for more information about Sulfamethoxazole-Trimethoprim Click here for more information about Trimetrexate glucuronate
Related publications: Amsden GW, Kowalsky SF, Morse GD. Trimetrexate for Pneumocystis carinii pneumonia in patients with AIDS. Ann Pharmacother. 1992 Feb;26(2):218-26. Review.
Last updated: June 23, 2005
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