A Controlled Trial Comparing the Efficacy of Aerosolized Pentamidine and Parenteral/Oral Sulfamethoxazole-Trimethoprim in the Treatment of Pneumocystis Carinii Pneumonia in AIDS
Information source: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Pneumonia, Pneumocystis Carinii; HIV Infections
Intervention: Pentamidine isethionate (Drug); Sulfamethoxazole-Trimethoprim (Drug)
Phase: Phase 3
Status: Completed
Sponsored by: National Institute of Allergy and Infectious Diseases (NIAID) Official(s) and/or principal investigator(s):
B Montgomery, Study Chair
Summary
To compare the safety and effectiveness of drug therapy with aerosolized pentamidine (PEN)
with that of conventional therapy, sulfamethoxazole plus trimethoprim (SMX/TMP) in the
treatment of Pneumocystis carinii pneumonia (PCP) in patients who have AIDS, are HIV
positive, or are at high risk for HIV infection.
New treatments are needed for PCP, a common lung infection in patients with AIDS, because
many patients treated with the two standard treatments, PEN given by injections and SMX/TMP,
have had adverse effects that required a change in treatment. There is also a high relapse
rate after the standard treatments. Preliminary experiments in humans suggest that
aerosolized PEN is as effective as the standard treatments for PCP, and causes few adverse
effects.
Clinical Details
Official title: A Controlled Trial Comparing the Efficacy of Aerosolized Pentamidine and Parenteral/Oral Trimethoprim-Sulfamethoxazole in the Treatment of Pneumocystis Pneumonia in AIDS
Study design: Intervention Model: Parallel Assignment, Primary Purpose: Treatment
Detailed description:
New treatments are needed for PCP, a common lung infection in patients with AIDS, because
many patients treated with the two standard treatments, PEN given by injections and SMX/TMP,
have had adverse effects that required a change in treatment. There is also a high relapse
rate after the standard treatments. Preliminary experiments in humans suggest that
aerosolized PEN is as effective as the standard treatments for PCP, and causes few adverse
effects.
Patients entered in the study are randomly assigned to aerosolized PEN or to intravenous
SMX/TMP, for a 21-day trial. SMX/TMP is given 4 times a day and aerosolized PEN once a day.
Doses are determined by body size. Patients who receive aerosolized PEN also receive a
placebo intravenous injection and patients who receive SMX/TMP also receive a placebo
aerosol. Patients are hospitalized at least 5 days. Patients who improve may be discharged
after 5 days at the discretion of the attending physician. Discharged patients continue the
study with oral SMX/TMP and aerosolized placebo or aerosolized PEN and oral placebo.
Patients who fail to respond or who develop severe adverse effects are switched to
intravenous PEN or other standard therapy. During the 21-day trial, zidovudine (AZT) may not
be used. AZT may be resumed after therapy for the acute PCP episode is completed.
Eligibility
Minimum age: 12 Years.
Maximum age: N/A.
Gender(s): Both.
Criteria:
Inclusion Criteria
Prior Medication:
Allowed:
- Zidovudine (AZT), but must be suspended during study medication.
Unequivocal diagnosis of Pneumocystis carinii pneumonia 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 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 5 days of randomization, the patient will be withdrawn from study
therapy. Resting (A-a) DO2 less than 30 torr on room air at all ACTG sites except San
Francisco General Hospital. Non-ACTG sites will enter patients up to a resting (A-a)
DO2less than 55 mmHg on room air.
Exclusion Criteria
Co-existing Condition:
Patients with the following are excluded:
- Dyspnea, cough, bronchospasm, or other reasons causing inability to cooperate with
aerosol administration.
- History of major adverse reaction to pentamidine or sulfonamide-containing
preparation defined as:
- Absolute neutropenia of 750 or less PMN + bands cells/mm3.
- Thrombocytopenia below 40000 platelets/mm3.
- Rise in creatinine:
- To more than 3. 0 mg/dl.
- Liver function abnormalities:
- SGOT or SGPT greater than 5 x upper limit of normal.
- Hypoglycemia below 50 mg/dl.
- Rash:
- Exfoliative or mucositis.
- Cough:
- Unremitting or bronchospasm uncontrolled by bronchodilator preventing more than 50
percent of delivered dose for more than 2 days.
Concurrent Medication:
Excluded:
- Other drugs for the treatment or prevention of AIDS or Pneumocystis carinii
pneumonia.
- Zidovudine (AZT).
Patients with the following are excluded:
- Dyspnea, cough, bronchospasm, or other reasons causing inability to cooperate with
aerosol administration.
- History of major adverse reaction to pentamidine or sulfonamide-containing
preparation defined as:
- Absolute neutropenia of 750 or less PMN + bands cells/mm3.
- Thrombocytopenia lower than 40000 platelets/mm3.
- Rise in creatinine:
- To greater than 3. 0 mg/dl.
- Liver function abnormalities:
- SGOT or SGPT greater than 5 x upper limit of normal.
- Hypoglycemia less than 50 mg/dl.
- Rash:
- Exfoliative or mucositis.
- Cough:
- Unremitting or bronchospasm uncontrolled by bronchodilator preventing more than 50
percent of delivered dose for more than 2 days.
Prior Medication:
Excluded within 14 days of study entry:
- Systemic steroids higher than adrenal replacement doses.
- Excluded within 6 weeks of study entry:
- Another antiprotozoal regimen for this episode, whether therapeutic or prophylactic.
- Sulfamethoxazole / trimethoprim.
- Pyrimethamine.
- Sulfadoxine / pyrimethamine.
- Pentamidine.
- Eflornithine.
Locations and Contacts
Tulane Univ School of Medicine, New Orleans, Louisiana 70112, United States
Harvard (Massachusetts Gen Hosp), Boston, Massachusetts 02114, United States
Bronx Municipal Hosp Ctr/Jacobi Med Ctr, Bronx, New York 10461, United States
Mount Sinai Med Ctr, New York, New York 10029, United States
Univ of Rochester Medical Center, Rochester, New York 14642, United States
Univ of North Carolina, Chapel Hill, North Carolina 275997215, United States
Holmes Hosp / Univ of Cincinnati Med Ctr, Cincinnati, Ohio 452670405, United States
Univ Hosp of Cleveland / Case Western Reserve Univ, Cleveland, Ohio 44106, United States
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
Related publications: Montgomery AB, Feigal DW Jr, Sattler F, Mason GR, Catanzaro A, Edison R, Markowitz N, Johnson E, Ogawa S, Rovzar M, et al. Pentamidine aerosol versus trimethoprim-sulfamethoxazole for Pneumocystis carinii in acquired immune deficiency syndrome. Am J Respir Crit Care Med. 1995 Apr;151(4):1068-74.
Last updated: March 28, 2012
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