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

November 2, 1999
March 28, 2012
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Complete list of historical versions of study NCT00000974 on ClinicalTrials.gov Archive Site
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A Study of Two Forms of Pentamidine in HIV-Infected Children Who May Have Pneumocystis Carinii Pneumonia
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

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.

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).

Interventional
Phase 1
Endpoint Classification: Pharmacokinetics Study
Masking: Open Label
Primary Purpose: Treatment
  • Pneumonia, Pneumocystis Carinii
  • HIV Infections
Drug: Pentamidine isethionate
Not Provided
  • 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)

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
16
September 1996
Not Provided

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.

Both
2 Months to 13 Years
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00000974
ACTG 115, 11090
Not Provided
National Institute of Allergy and Infectious Diseases (NIAID)
National Institute of Allergy and Infectious Diseases (NIAID)
Not Provided
Study Chair: YJ Bryson
Study Chair: ER Stiehm
Study Chair: B Montgomery
National Institute of Allergy and Infectious Diseases (NIAID)
March 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP