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Pneumonia, Pneumocystis CariniiPhase 3NCT00000727

A Controlled Comparative Trial of Sulfamethoxazole-Trimethoprim Versus Aerosolized Pentamidine for Secondary Prophylaxis of Pneumocystis Carinii Pneumonia in AIDS Patients Receiving Azidothymidine (AZT)

A Phase 3 study testing Pentamidine isethionate, Pyrimethamine and Sulfamethoxazole/Trimethoprim in people with Pneumonia, Pneumocystis Carinii and HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 9 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

To determine if the drug combination sulfamethoxazole-trimethoprim (SMX-TMP), given by mouth, and the drug pentamidine (PEN), given by inhaled aerosol, are effective in preventing a relapse of Pneumocystis carinii pneumonia (PCP) when they are given to patients who have recovered from a first episode of PCP and are… Read more about this study

Who is it for?
Ages 12 years and older
What is being tested?
Pentamidine isethionate, Pyrimethamine and Sulfamethoxazole/Trimethoprim
How many people
322 participants
Where
9 sitesUnited States
Study dates
Start not givento Aug 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

  • Patients must fulfill the following criteria:
  • Randomization within 10 weeks of completing therapy for Pneumocystis carinii pneumonia (PCP).
  • Ability to tolerate oral and aerosolized therapy at the time of randomization.
  • Life expectancy > 4 months.
  • Concurrent Medication:
  • Allowed:
Show all 29Show fewer
  • Inhaled bronchodilators for cough and bronchospasm related to aerosolized pentamidine treatment.
  • Aspirin at modest doses.
  • Ibuprofen at modest doses.
  • Acetaminophen at modest doses.
  • Erythropoietin for management of anemia.
  • Allowed to treat opportunistic infections while on study:
  • Acyclovir.
  • Ketoconazole.
  • Amphotericin B.
  • Nystatin.
  • Clotrimazole.
  • Also allowed:
  • Ganciclovir (DHPG) for maintenance therapy of life-threatening or sight-threatening cytomegalovirus retinitis (CMV retinitis) infection only.
  • Zidovudine (AZT) must be discontinued during the acute induction phase of treatment and will be restarted when maintenance therapy is introduced.
  • Concurrent Treatment:
  • Allowed:
  • Local radiation therapy for Kaposi's sarcoma.
  • Prior Medication:
  • Allowed:
  • Primary prophylactic therapy prior to Pneumocystis carinii pneumonia (PCP) episode.
  • Risk Behavior:
  • Allowed:
  • Patients maintained in a methadone maintenance program per local investigator's judgment.

Who cannot join

  • Active drug or alcohol abuse which would impair performance as a study subject.
  • Concurrent Medication:
  • Excluded:
  • Famotidine.
  • Any medications suspected of interference with the metabolism of zidovudine.
  • Flurazepam.
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  • Chronic probenecid.
  • Phenobarbital.
  • Phenytoin.
  • Experimental therapies, except as noted.
  • Chronic oral bronchodilators should not be started in patients in order to maintain them on aerosolized pentamidine after they have exhibited pulmonary toxicity.
  • Prior Medication:
  • Excluded for the 30 patients who will undergo pharmacokinetic studies:
  • Zidovudine (AZT) at any time.
  • Excluded within 7 days of study entry for the 30 patients who will undergo pharmacokinetic studies:
  • Trimethoprim / sulfamethoxazole.
  • Pyrimethamine / sulfadoxine.
  • Aerosolized pentamidine.
  • Excluded:
  • Pentamidine by any route for the original infection.
  • Prophylactic therapy for Pneumocystis carinii pneumonia (PCP) between the discontinuation of acute treatment and study entry.
  • Prior Treatment:
  • Excluded within 2 weeks of study entry:
  • Transfusions of blood or red blood cells.
  • Patients may not have any of the following symptoms or diseases:
  • Known treatment-limiting hypersensitivity to sulfonamides, trimethoprim, pyrimethamine, pentamidine, or zidovudine (AZT), especially but not limited to, exfoliative dermatitis, erythema multiforme, and Stevens-Johnson syndrome.
  • Development of severe hypoglycemia (serum glucose < 50 mg/dl with pentamidine therapy).
  • History of neoplasms other than basal cell carcinoma of the skin or carcinoma in situ of the cervix, or mucocutaneous Kaposi's sarcoma.
  • Known visceral Kaposi's sarcoma.
  • Known glucose-6-phosphate dehydrogenase (G-6-PD) deficiency.

Trial locations and contacts

9 sites in 1 country.

9 sites in 1 country

United States9 sites

  • Bmc Actg Crs

    Boston, Massachusetts, 02118

  • Case CRS

    Cleveland, Ohio, 44106

  • Indiana Univ. School of Medicine, Infectious Disease Research Clinic

    Indianapolis, Indiana, 46202

  • USC CRS

    Los Angeles, California, 90033

  • University of Minnesota, ACTU

    Minneapolis, Minnesota, 55455

  • Memorial Sloan-Kettering Cancer Ctr.

    New York, New York, 10021

  • Ucsd, Avrc Crs

    San Diego, California, 92103

  • Ucsf Aids Crs

    San Francisco, California, 94110

  • University of Washington AIDS CRS

    Seattle, Washington, 98105

Other trials in United States

About this study

Official title: A Controlled Comparative Trial of Trimethoprim - Sulfamethoxazole Versus Aerosolized Pentamidine for Secondary Prophylaxis of Pneumocystis Carinii Pneumonia in AIDS Patients Receiving Azidothymidine (AZT)

To determine if the drug combination sulfamethoxazole-trimethoprim (SMX-TMP), given by mouth, and the drug pentamidine (PEN), given by inhaled aerosol, are effective in preventing a relapse of Pneumocystis carinii pneumonia (PCP) when they are given to patients who have recovered from a first episode of PCP and are being given zidovudine (AZT) to treat primary HIV infection.

AZT prolongs survival in patients with AIDS and decreases the occurrence of opportunistic infections such as PCP. However, PCP recurs in about 43 percent of patients receiving AZT, indicating a need for other treatments to reduce the relapse rate.

The two medications to be tested in this study, SMX/TMP and aerosolized PEN, have also been partially effective in preventing recurrence of PCP. It is hoped that the combination of AZT with these medications will be more effective than AZT or one of the medications alone.

Read the detailed description

AZT prolongs survival in patients with AIDS and decreases the occurrence of opportunistic infections such as PCP. However, PCP recurs in about 43 percent of patients receiving AZT, indicating a need for other treatments to reduce the relapse rate.

The two medications to be tested in this study, SMX/TMP and aerosolized PEN, have also been partially effective in preventing recurrence of PCP. It is hoped that the combination of AZT with these medications will be more effective than AZT or one of the medications alone.

Patients receive the standard dose of AZT at study entry. Low body weight patients receive AZT at a lower dose. Patients are randomly assigned to one of two medications intended to prevent the recurrence of PCP. Patients assigned to SMX/TMP will take 1 capsule which contains both drugs once a day for 1 year. Patients assigned to PEN will have 1 aerosol treatment every 4 weeks for 1 year. Blood will be drawn at intervals in order to estimate blood levels of the drugs and to detect any adverse effects from the drugs. Note: Earlier versions of this protocol reflect its original design as a 3-arm study comparing aerosolized PEN, SMX/TMP, and pyrimethamine-sulfadoxine as secondary prophylaxis of PCP in AIDS patients receiving AZT. In order to reduce the effective sample size and permit the completion of accrual in a reasonable period of time, the pyrimethamine - sulfadoxine arm of this study has been discontinued. Patients randomized to this arm will be continued in this study on the original randomized therapy. Management of these patients will follow that described for SMX/TMP in the latest protocol version. AMENDED: Lower dose of AZT allowed.

Being tested
Pentamidine isethionate, Pyrimethamine, Sulfamethoxazole/Trimethoprim, Sulfadoxine/Pyrimethamine, Zidovudine
Keywords
Sulfadoxine, Trimethoprim-Sulfamethoxazole Combination, AIDS-Related Opportunistic Infections, Pneumonia, Pneumocystis carinii, Pentamidine, Pyrimethamine, Drug Evaluation, Administration, Inhalation, Administration, Oral, Aerosols, Acquired Immunodeficiency Syndrome, Zidovudine
Medical subject headings
Pneumonia, Pneumocystis, HIV Infections, AIDS-Related Opportunistic Infections, Respiratory Aspiration, Acquired Immunodeficiency Syndrome

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Pentamidine isethionateDrug

  • PyrimethamineDrug

  • Sulfamethoxazole/TrimethoprimDrug

  • Sulfadoxine/PyrimethamineDrug

  • ZidovudineDrug

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted31 Aug 2001 (estimated)
  2. Study completionAug 1991

Resources

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
322 participants
IDs, dates and publications
ClinicalTrials.gov ID
NCT00000727
Sponsor's protocol ID
ACTG 021
Other IDs
10997
Status last verified
Oct 2021
First submitted
2 Nov 1999
Last updated
3 Nov 2021
Results posted
No

Publications

  • Freedberg KA, Hardy WD, Holzman RS, Tosteson AN, Craven DE. Validating literature-based models with direct clinical trial results: the cost-effectiveness of secondary prophylaxis for PCP in AIDS patients. Med Decis Making. 1996 Jan-Mar;16(1):29-35. doi: 10.1177/0272989X9601600110.

    PubMed 8717596

  • Hardy WD, Feinberg J, Finkelstein DM, Power ME, He W, Kaczka C, Frame PT, Holmes M, Waskin H, Fass RJ, et al. A controlled trial of trimethoprim-sulfamethoxazole or aerosolized pentamidine for secondary prophylaxis of Pneumocystis carinii pneumonia in patients with the acquired immunodeficiency syndrome. AIDS Clinical Trials Group Protocol 021. N Engl J Med. 1992 Dec 24;327(26):1842-8. doi: 10.1056/NEJM199212243272604.

    PubMed 1448121

  • Hardy WD, Holzman RS, Avramis V, Bawdon R, Fall H, Feinberg J. Clinical and pharmacokinetic interactions of combined zidovudine (ZDV) therapy and sulfadoxine-pyrimethamine (fansidar) prophylaxis in post-PCP AIDS patients (ACTG 021). Int Conf AIDS. 1989 Jun 4-9;5:294 (abstract no TBP46)

  • Robins JM, Finkelstein DM. Correcting for noncompliance and dependent censoring in an AIDS Clinical Trial with inverse probability of censoring weighted (IPCW) log-rank tests. Biometrics. 2000 Sep;56(3):779-88. doi: 10.1111/j.0006-341x.2000.00779.x.

    PubMed 10985216

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Pentamidine isethionate, Pyrimethamine and Sulfamethoxazole/Trimethoprim in people with Pneumonia, Pneumocystis Carinii and HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 9 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 29 inclusion and 30 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 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 9 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 NCT00000727, which also lists 4 linked publications.

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.

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