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

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID) (NIH)

Overall Status

Completed

CT.gov ID

NCT00000974

Collaborator

(none)

Enrollment

Locations

Patients Per Site

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Pneumonia, Pneumocystis Carinii HIV Infections	Drug: Pentamidine isethionate	Phase 1

Detailed Description

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).

Study Design

Study Type:

Interventional

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase I Study of the Safety, Tolerance, and Study of the Pharmacokinetics of Aerosolized Pentamidine and Parenteral Pentamidine in Children With HIV Infection and Suspected Pneumocystis Carinii Pneumonia

Actual Study Completion Date :

Sep 1, 1996

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

2 Months to 13 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Childrens Hosp. LA - Dept. of Ped., Div. of Clinical Immunology & Allergy	Los Angeles	California	United States	90027
2	UCLA-Los Angeles/Brazil AIDS Consortium (LABAC) CRS	Los Angeles	California	United States	90095
3	Children's Hosp. & Research Ctr. Oakland, Ped. Clinical Research Ctr. & Research Lab.	Oakland	California	United States	94609
4	Texas Children's Hosp. CRS	Houston	Texas	United States	77030