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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00000974
First received: November 2, 1999
Last updated: March 28, 2012
Last verified: March 2012
  Purpose

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 Intervention Phase
Pneumonia, Pneumocystis Carinii
HIV Infections
Drug: Pentamidine isethionate
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Pharmacokinetics Study
Masking: 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

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Estimated Enrollment: 16
Study Completion Date: September 1996
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).

  Eligibility

Ages Eligible for Study:   2 Months to 13 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00000974

Locations
United States, California
UCLA-Los Angeles/Brazil AIDS Consortium (LABAC) CRS
Los Angeles, California, United States, 90095
Childrens Hosp. LA - Dept. of Ped., Div. of Clinical Immunology & Allergy
Los Angeles, California, United States, 90027
Children's Hosp. & Research Ctr. Oakland, Ped. Clinical Research Ctr. & Research Lab.
Oakland, California, United States, 94609
United States, Texas
Texas Children's Hosp. CRS
Houston, Texas, United States, 77030
Sponsors and Collaborators
Investigators
Study Chair: YJ Bryson
Study Chair: ER Stiehm
Study Chair: B Montgomery
  More Information

Additional Information:
Publications:
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)
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)

Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00000974     History of Changes
Other Study ID Numbers: ACTG 115, 11090
Study First Received: November 2, 1999
Last Updated: March 28, 2012
Health Authority: United States: Federal Government

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
AIDS-Related Opportunistic Infections
Pneumonia, Pneumocystis carinii
Pentamidine
Injections, Intravenous
Drug Evaluation
Aerosols
Acquired Immunodeficiency Syndrome

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Pneumonia
Pneumonia, Pneumocystis
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Lung Diseases
Respiratory Tract Diseases
Respiratory Tract Infections
Lung Diseases, Fungal
Mycoses
Pneumocystis Infections
Pentamidine
Antifungal Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Antiprotozoal Agents
Antiparasitic Agents
Trypanocidal Agents

ClinicalTrials.gov processed this record on July 23, 2014