Aerosols in the Treatment of Pneumocystis Pneumonia: A Pilot Study Quantitating the Deposition of Aerosolized Pentamidine as Delivered in ACTG 040 and Comparing Its Toxicity With Parenteral Pentamidine Therapy

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00000722
First received: November 2, 1999
Last updated: March 28, 2012
Last verified: March 2012
  Purpose

To compare the use of pentamidine aerosol (inhaled mist) with the standard intravenous method of administration in patients with AIDS related Pneumocystis carinii pneumonia (PCP), to measure the amount of pentamidine aerosol that actually reaches the lung, and to see if close clinical observation is safer and as effective as drug therapy in the prevention of PCP recurrences. To compare the efficiency of 2 nebulizers - the Respirgard II nebulizer and the Cadema Aerotech II nebulizer. Aerosolized pentamidine was as effective as intravenous pentamidine in treating PCP in animals. More of the pentamidine reached the lungs and less was found in the liver and kidney after pentamidine was given by aerosol than after an intravenous injection. This suggests that the toxicity of pentamidine may be less if given by aerosol than if given by the intravenous route.


Condition Intervention
Pneumonia, Pneumocystis Carinii
HIV Infections
Drug: Pentamidine isethionate

Study Type: Interventional
Study Design: Intervention Model: Parallel Assignment
Primary Purpose: Treatment
Official Title: Aerosols in the Treatment of Pneumocystis Pneumonia: A Pilot Study Quantitating the Deposition of Aerosolized Pentamidine as Delivered in ACTG 040 and Comparing Its Toxicity With Parenteral Pentamidine Therapy

Resource links provided by NLM:


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

Estimated Enrollment: 45
Study Completion Date: June 1991
Detailed Description:

Aerosolized pentamidine was as effective as intravenous pentamidine in treating PCP in animals. More of the pentamidine reached the lungs and less was found in the liver and kidney after pentamidine was given by aerosol than after an intravenous injection. This suggests that the toxicity of pentamidine may be less if given by aerosol than if given by the intravenous route.

Patients will inhale one dose of radiolabeled aerosol containing pentamidine, and an image of the lung will be taken immediately and then 24 hours later to determine the amount of pentamidine reaching the various areas of the lung. Patients will then undergo a bronchoalveolar lavage (BAL) in order to recover the PCP organism from the lung and to corroborate the diagnosis of PCP. If PCP organisms are detected, patients will be randomly assigned to aerosolized or intravenous pentamidine and treated for 21 days. Patients taking pentamidine by aerosol will repeat the radiolabeled aerosol study on day 9. The BAL will be repeated at the end of therapy for all patients. If patients do not improve within 9 days, they will be switched to another therapy. After completion of therapy, patients will be given the option of prophylactic therapy, i.e., doses of medication to prevent reinfection, for PCP. All patients will be carefully assessed every 4 weeks for 6 months whether they begin prophylactic therapy or not. Zidovudine (AZT) may not be taken during the 21-day trial because of the increased risk of side effects, but it can be resumed when PCP therapy is completed.

  Eligibility

Ages Eligible for Study:   12 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

Prior Medication:

Allowed:

  • Prophylaxis for Pneumocystis carinii pneumonia (PCP); zidovudine.

Unequivocal diagnosis of Pneumocystis carinii pneumonia (PCP) established by morphological confirmation of three or more typical Pneumocystis carinii organisms in bronchoalveolar lavage fluid, obtained immediately following the initial inhalation of radiolabeled aerosol.

  • Resting (A-a) DO2 < 30 torr on room air or resting (A-a) DO2 = or < 55 torr on room air with a serious intolerance to trimethoprim / sulfamethoxazole (TMP / SMX), defined as one or more of the following:
  • Platelets < 50000 platelets/mm3 or absolute neutrophil count (polys plus bands) = or < 500 cells/mm3 on at least two occasions = or > 12 hours apart.
  • Blistering rash, mucosal involvement, generalized maculopapular eruption, or intolerable pruritus.
  • Transaminase > 5 x ULN or = or > 300 IU if baseline is abnormal.
  • Daily temperature = or > 103 degrees F beginning after the 5th day of treatment and persisting for at least 3 days and not responsive to antipyretic therapy, with no other discernible cause.
  • Any other severe or life-threatening adverse reaction to TMP / SMX that, in the investigator's opinion, makes continued or recurrent treatment with TMP / SMX inadvisable (approved on a case-by-case basis by the NIAID clinical monitor).

Exclusion Criteria

Co-existing Condition:

Patients with the following conditions or diseases are excluded:

  • Dyspnea, cough, bronchospasm, or other reasons causing inability to cooperate with aerosol administration.
  • History of major adverse reaction to pentamidine.

Patients with the following conditions or diseases are excluded:

  • Dyspnea, cough, bronchospasm, or other reasons causing inability to cooperate with aerosol administration.
  • History of major adverse reaction to pentamidine.

Prior Medication:

Excluded:

  • Other antiprotozoal regimens.
  • Excluded within 14 days of entry:
  • Systemic steroids > adrenal replacement doses
  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: NCT00000722

Locations
United States, New York
SUNY - Stony Brook
Stony Brook, New York, United States, 117948153
Sponsors and Collaborators
Investigators
Study Chair: Smaldone GC
  More Information

Additional Information:
Publications:
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00000722     History of Changes
Other Study ID Numbers: ACTG 041, 11016
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
Lung
Administration, Inhalation
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 August 19, 2014