Clinical trial NCT00001996: A Phase II Open Randomized Comparison of 566C80 and Pentamidine Isethionate for the Treatment of Pneumocystis Carinii Pneumonia in AIDS Patients Who Are Intolerant of Trimethoprim / Sulfamethoxazole
Official title: A Phase II Open Randomized Comparison of 566C80 and Pentamidine Isethionate for the Treatment of Pneumocystis Carinii Pneumonia in AIDS Patients Who Are Intolerant of Trimethoprim / Sulfamethoxazole
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Pneumonia, Pneumocystis Carinii
HIV Infections
Keywords: Trimethoprim-Sulfamethoxazole Combination
Pneumonia, Pneumocystis carinii
Pentamidine
Acquired Immunodeficiency Syndrome
atovaquone
Lead sponsor: NIH AIDS Clinical Trials Information Service
Sponsor class: INDUSTRY
First posted: 2001-08-31
Sex: ALL
Minimum age (years): 13
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief summary: To compare the safety of atovaquone (566C80) with intravenous (IV) pentamidine for the treatment of mild to moderate Pneumocystis carinii pneumonia (PCP) in AIDS patients who are intolerant of therapy with trimethoprim / sulfamethoxazole (TMP / SMX) by comparing the incidence of premature discontinuation of therapy due to toxicity. To compare the efficacy of 566C80 with intravenous (IV) pentamidine for the treatment of mild to moderate PCP in the same population.


Eligibility criteria: Inclusion Criteria

Patients must have the following:

* History of, or are currently experiencing, intolerance to TMP / SMX, or to another sulfonamide, which required discontinuation of therapy.
* Pneumocystis carinii pneumonia (PCP).
* Willing and able to give informed consent.

Exclusion Criteria

Co-existing Condition:

Patients with the following conditions or symptoms are excluded.

* Malabsorption disorder or vomiting that would, in the judgement of the investigator, potentially limit the retention and absorption of an oral therapy.
* Concurrent bacterial, fungal, or viral pneumonitis, pulmonary Kaposi's sarcoma, or other concurrent illness, or chronic pulmonary disease that, in the investigator's opinion, would make interpretation of drug efficacy difficult.
* Present occurrences of abnormal prolongation of QT interval on standard, 12 lead EKG.

Concurrent Medication:

Excluded:

* Drugs with potential anti-pneumocystis effect (eg:
* sulfonamides, dapsone, trimethoprim, other dihydrofolate reductase (DHFR) inhibitors, primaquine, clindamycin, sulfonylureas).
* Ganciclovir.
* Zidovudine.
* Investigational agents including anti-retroviral agents (ddI, ddC, etc.). Patients receiving these drugs prior to entry must discontinue their use during the therapy phase (21 days) of the trial.
* Corticosteroids (except replacement therapy) during the 21 day treatment period (Strata A and C Patients).
* Class 1A antiarrhythmics (ie:
* quinidine, procainamide, disopyramide).

Patients with the following are excluded:

* Judged by the investigator to be in impending respiratory failure.
* Known intolerance to parenteral pentamidine isethionate, or therapeutic failure with same for treatment of current episode of PCP.
* Significant psychosis or emotional disorder that, in the investigator's opinion, would preclude the patient from adhering to the protocol.
* Inability or unwillingness to take medication orally or with food.
* Prior documented glucose-6-phosphate dehydrogenase (G6PD) deficiency.
* History, or present occurrences, of abnormal prolongation of QT interval on standard, 12 lead EKG.
* Termination from FDA 053A due to toxicity.
* For patients entering under historic intolerance criteria (Groups A and B), prior therapy for this episode of PCP is an exclusion.

Prior Medication:

Excluded:

* Treatment within 4 weeks of entry for a prior episode of PCP.
* For patients entering under historic intolerance criteria (Groups A and B), prior therapy for this episode of PCP is an exclusion.

Required:

* Adjuvant prednisone for patient enrolled in Strata B or D.

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Berkeley
country: United States
facility: East Bay AIDS Ctr
state: California
city: Harbor City
country: United States
facility: Kaiser Foundation Hosp
state: California
city: Los Angeles
country: United States
facility: Cedars Sinai Med Ctr
state: California
city: Los Angeles
country: United States
facility: UCLA CARE Ctr
state: California
city: Orange
country: United States
facility: UCI Med Ctr
state: California
city: Redwood City
country: United States
facility: AIDS Community Research Consortium
state: California
city: San Francisco
country: United States
facility: Davies Med Ctr
state: California
city: San Ramone
country: United States
facility: Dr Patrick Joseph
state: California
city: Atlanta
country: United States
facility: Infectious Disease Research Consortium of Georgia
state: Georgia
city: Boston
country: United States
facility: Massachusetts Gen Hosp
state: Massachusetts
city: Boston
country: United States
facility: Boston City Hosp
state: Massachusetts
city: New York
country: United States
facility: Beth Israel Med Ctr
state: New York
city: New York
country: United States
facility: Saint Vincent's Hosp and Med Ctr
state: New York
city: New York
country: United States
facility: Harlem AIDS Treatment Group / Harlem Hosp Ctr
state: New York
city: Cincinnati
country: United States
facility: Univ of Cincinnati
state: Ohio
city: Portland
country: United States
facility: Portland Veterans Adm Med Ctr / Rsch & Education Grp
state: Oregon
city: Philadelphia
country: United States
facility: Buckley Braffman Stern Med Associates
state: Pennsylvania
city: Memphis
country: United States
facility: Regional Med Ctr at Memphis
state: Tennessee
city: Houston
country: United States
facility: Gathe, Joseph, M.D.
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
Study officials:
References:
citation: Dohn M, Weinberg W, Rosenstock J, Follansbee S, Torres R, Caldwell P. Atovaquone vs. pentamidine for pneumocystis carinii pneumonia in patients with AIDS. Int Conf AIDS. 1993 Jun 6-11;9(1):372 (abstract no PO-B10-1421)