Clinical trial NCT00000771: A Double-Blind, Placebo-Controlled Trial of Paromomycin for Treatment of Cryptosporidiosis in Patients With Advanced HIV Disease and CD4 Counts Under 150 Cells/mm3
Official title: A Double-Blind, Placebo-Controlled Trial of Paromomycin for Treatment of Cryptosporidiosis in Patients With Advanced HIV Disease and CD4 Counts Under 150 Cells/mm3
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Cryptosporidiosis
HIV Infections
Keywords: Cryptosporidiosis
Acquired Immunodeficiency Syndrome
Paromomycin
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
First posted: 2001-08-31
Enrollment: 68
Sex: ALL
Minimum age (years): 13
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: To determine the effectiveness of oral paromomycin sulfate for 21 days compared to placebo in the treatment of cryptosporidiosis in patients with HIV infection. To evaluate the safety of oral paromomycin at two different doses. To explore whether paromomycin administered over a longer period provides additional benefit.

In previous studies, patients with cryptosporidiosis demonstrated dramatic improvement with paromomycin therapy.

Detailed description: In previous studies, patients with cryptosporidiosis demonstrated dramatic improvement with paromomycin therapy.

Patients are randomized to receive either placebo or paromomycin for 3 weeks. After the initial double-blind phase, all patients receive open-label paromomycin for 3 weeks. Following 6 weeks of therapy, patients who do not achieve a complete response receive a higher dose of paromomycin for an additional 3 weeks, while complete responders continue receiving the original dose for an additional 3 weeks. Complete or partial responders after 9 weeks may receive 16 additional weeks of optional maintenance therapy at the dose at which their response was achieved. Treatment continues for up to 25 weeks total. Patients are followed at weeks 1, 3, 4, 6, 7, and 9, and then at 2-4 week intervals.

Eligibility criteria: Inclusion Criteria

Concurrent Medication:

Allowed:

* Antiretroviral therapy.
* Macrolides for disseminated Mycobacterium avium.
* Atovaquone for toxoplasmosis.
* Other antimicrobials for concurrent infections.
* Lomotil, Imodium, or deodorized opium tincture in a standardized regimen for diarrhea.

Patients must have:

* Advanced HIV disease.
* Diarrhea presumptively caused by Cryptosporidia.

Exclusion Criteria

Co-existing Condition:

Patients with the following symptoms or conditions are excluded:

* Hypersensitivity to aminoglycosides.
* Inability to swallow capsules.
* Active infection due to other enteric pathogens. Previous diagnosis of CMV or MAC infection permitted if patient is currently stabilized on a therapeutic regimen (clarithromycin up to 500 mg bid or azithromycin up to 600 mg daily).
* Other known causes for diarrhea (e.g., malabsorption syndrome, gastrointestinal Kaposi's sarcoma).

Concurrent Medication:

Excluded during the first 9 weeks of study:

* Agents with putative anticryptosporidial activity (such as spiramycin, diclazuril, letrazuril, or bovine colostrum).
* Octreotide acetate (Sandostatin).
* Antidiarrheals other than those specifically allowed.
* Clarithromycin if initiated at 500 mg or higher or azithromycin if initiated at 600 mg or higher.

Prior Medication:

Excluded:

* Paromomycin at \> 1 g/day for \>= 14 days prior to study entry.

Excluded within 14 days prior to study entry:

* Agents with putative anticryptosporidial activity (such as spiramycin, diclazuril, letrazuril, or bovine colostrum), with the exception of macrolides that are permitted for other indications.
* Octreotide acetate (Sandostatin).

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: USC CRS
state: California
city: Miami
country: United States
facility: Univ. of Miami AIDS CRS
state: Florida
city: Chicago
country: United States
facility: Northwestern University CRS
state: Illinois
city: Chicago
country: United States
facility: Rush Univ. Med. Ctr. ACTG CRS
state: Illinois
city: Chicago
country: United States
facility: Weiss Memorial Hosp.
state: Illinois
city: Indianapolis
country: United States
facility: Indiana Univ. School of Medicine, Infectious Disease Research Clinic
state: Indiana
city: Indianapolis
country: United States
facility: Methodist Hosp. of Indiana
state: Indiana
city: Saint Louis
country: United States
facility: Washington U CRS
state: Missouri
city: Buffalo
country: United States
facility: SUNY - Buffalo, Erie County Medical Ctr.
state: New York
city: New York
country: United States
facility: NY Univ. HIV/AIDS CRS
state: New York
city: New York
country: United States
facility: Cornell University A2201
state: New York
city: Cincinnati
country: United States
facility: Univ. of Cincinnati CRS
state: Ohio
city: Cleveland
country: United States
facility: Case CRS
state: Ohio
city: Columbus
country: United States
facility: The Ohio State Univ. AIDS CRS
state: Ohio
city: San Juan
country: Puerto Rico
facility: Puerto Rico-AIDS CRS
Study officials:
name: Carey J
role: STUDY_CHAIR
References:
citation: Hewitt RG, Yiannoutsos CT, Higgs ES, Carey JT, Geiseler PJ, Soave R, Rosenberg R, Vazquez GJ, Wheat LJ, Fass RJ, Antoninievic Z, Walawander AL, Flanigan TP, Bender JF. Paromomycin: no more effective than placebo for treatment of cryptosporidiosis in patients with advanced human immunodeficiency virus infection. AIDS Clinical Trial Group. Clin Infect Dis. 2000 Oct;31(4):1084-92. doi: 10.1086/318155. Epub 2000 Oct 25.