A Study of Two Forms of Pentamidine in HIV-Infected Children Who May Have Pneumocystis Carinii Pneumonia

NCT ID: NCT00000974

Last Updated: 2021-11-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 16 participants
• Study Classification: INTERVENTIONAL
• Study Completion Date: 1996-09-30

Brief Summary

To evaluate the delivery of a single dose of aerosolized pentamidine to children; to evaluate the tolerance of pentamidine administration by mask; to compare intravenous pentamidine first dose pharmacokinetics (blood levels) in children with information previously collected on adults; and to compare plasma pentamidine levels in children after an aerosolized treatment with levels previously collected on adults.

Pneumocystis carinii pneumonia (PCP) is the most common serious infection in children with AIDS and is associated with a high death rate. Current approved treatment includes intravenous trimethoprim - sulfamethoxazole (TMP / SMX) and intravenous pentamidine, which are both effective in treatment of the first episode of PCP pneumonia. However, both therapies have a 50 percent or greater incidence of adverse reactions. Because of serious toxicities, drug treatment has had to be discontinued. Animal studies show that aerosolized pentamidine (pentamidine given through inhalation) is as effective as intravenous pentamidine. It is hoped that the aerosolized route will be less toxic than intravenous pentamidine. The study is the first step in evaluating the delivery of aerosolized pentamidine to children.

Detailed Description

Pneumocystis carinii pneumonia (PCP) is the most common serious infection in children with AIDS and is associated with a high death rate. Current approved treatment includes intravenous trimethoprim - sulfamethoxazole (TMP / SMX) and intravenous pentamidine, which are both effective in treatment of the first episode of PCP pneumonia. However, both therapies have a 50 percent or greater incidence of adverse reactions. Because of serious toxicities, drug treatment has had to be discontinued. Animal studies show that aerosolized pentamidine (pentamidine given through inhalation) is as effective as intravenous pentamidine. It is hoped that the aerosolized route will be less toxic than intravenous pentamidine. The study is the first step in evaluating the delivery of aerosolized pentamidine to children.

Sixteen patients are assigned into one of the following groups. Group 1 (four patients) receives intravenous pentamidine as a one-time dose, infused over 2 hours. Group 2a (six patients) receives aerosolized pentamidine via face mask. Group 2b (six patients) receives aerosolized pentamidine 2 times. Group 2b will be studied only if initial dose is well tolerated. Small amounts (1 - 2 cubic centimeters) of blood is taken from all groups at 40 minutes, and 2, 3, 7, 14, and 24 hours from the beginning of pentamidine treatment and at the same time as the lung biopsy or bronchial alveolar lavage. Patients are given routine TMP / SMX (or whatever medications are considered appropriate by the patient's primary physician for medical management) dosing 1 - 2 hours after pentamidine is given. Bronchial alveolar lavage fluid or lung tissue from biopsy will be obtained between 2 - 48 hours after initiation of pentamidine treatment (optionally 10 - 24 hours post dose).

Conditions

Pneumonia, Pneumocystis Carinii; HIV Infections

Keywords

AIDS-Related Opportunistic Infections; Pneumonia, Pneumocystis carinii; Pentamidine; Injections, Intravenous; Drug Evaluation; Aerosols; Acquired Immunodeficiency Syndrome

Study Design

• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Interventions

Pentamidine isethionate

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

Concurrent Medication:

Allowed:

• Routine trimethoprim / sulfamethoxazole (TMP / SMX) (or whatever medications are considered appropriate by the patient's primary physician for medical management) 1 - 2 hours after pentamidine is given.

Patients must have:

• HIV infection with suspected Pneumocystis carinii pneumonia (PCP).
• Parent(s) or legal guardian must sign an informed consent.

Exclusion Criteria

Co-existing Condition:

Patients with the following conditions or symptoms are excluded:

• Known history of reactive airway disease or another chronic lung disease.
• Known previous adverse reaction to pentamidine.
• Thrombocytopenia.

Patients with the following are excluded:

• History of reactive airway disease or another chronic lung disease.
• Known previous adverse reaction to pentamidine.

Unable to cooperate with administration of aerosol via face mask.

• Minimum Eligible Age: 2 Months
• Maximum Eligible Age: 13 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

YJ Bryson

Role: STUDY_CHAIR

ER Stiehm

Role: STUDY_CHAIR

B Montgomery

Role: STUDY_CHAIR

Locations

Childrens Hosp. LA - Dept. of Ped., Div. of Clinical Immunology & Allergy

Los Angeles, California, United States

UCLA-Los Angeles/Brazil AIDS Consortium (LABAC) CRS

Los Angeles, California, United States

Children's Hosp. & Research Ctr. Oakland, Ped. Clinical Research Ctr. & Research Lab.

Oakland, California, United States

Texas Children's Hosp. CRS

Houston, Texas, United States

Countries

United States

References

Conte JE Jr; Wara D. Pharmacokinetics of aerosolized pentamidine in children. Int Conf AIDS. 1993 Jun 6-11;9(1):381 (abstract no PO-B10-1477)

Reference Type: BACKGROUND

Kreuz W, Gunguor T, Funk M, Ehrenforth S, Linde R, Lotz C, Kornhuber B. First experience with Pneumocystis carinii pneumonia-prophylaxis by inhaled pentamidine in HIV-infected children. Int Conf AIDS. 1991 Jun 16-21;7(2):242 (abstract no WB2243)

Reference Type: BACKGROUND

Other Identifiers

11090

Identifier Type: REGISTRY

Identifier Source: secondary_id

ACTG 115

Identifier Type: -

Identifier Source: org_study_id