Clinical trial NCT00000715: A Controlled Trial Comparing the Efficacy of Aerosolized Pentamidine and Parenteral/Oral Sulfamethoxazole-Trimethoprim in the Treatment of Pneumocystis Carinii Pneumonia in AIDS
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Pneumonia, Pneumocystis Carinii
HIV Infections
Keywords: Trimethoprim-Sulfamethoxazole Combination
AIDS-Related Opportunistic Infections
Pneumonia, Pneumocystis carinii
Pentamidine
Infusions, Intravenous
Administration, Inhalation
Aerosols
Acquired Immunodeficiency Syndrome
Sulfamethoxazole-Trimethoprim
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
First posted: 2001-08-31
Enrollment: 240
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

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 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.

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: New Orleans
country: United States
facility: Tulane Univ School of Medicine
state: Louisiana
city: Boston
country: United States
facility: Harvard (Massachusetts Gen Hosp)
state: Massachusetts
city: Bronx
country: United States
facility: Bronx Municipal Hosp Ctr/Jacobi Med Ctr
state: New York
city: New York
country: United States
facility: Mount Sinai Med Ctr
state: New York
city: Rochester
country: United States
facility: Univ of Rochester Medical Center
state: New York
city: Chapel Hill
country: United States
facility: Univ of North Carolina
state: North Carolina
city: Cincinnati
country: United States
facility: Holmes Hosp / Univ of Cincinnati Med Ctr
state: Ohio
city: Cleveland
country: United States
facility: Univ Hosp of Cleveland / Case Western Reserve Univ
state: Ohio
city: West Columbia
country: United States
facility: Julio Arroyo
state: South Carolina
Study officials:
name: B Montgomery
role: STUDY_CHAIR
References:
citation: 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. doi: 10.1164/ajrccm/151.4.1068.