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A Study of Three Drugs Plus Zidovudine in the Prevention of Infections in HIV-Infected Patients
This study has been completed.
Sponsored by: National Institute of Allergy and Infectious Diseases (NIAID)
Information provided by: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00000991
  Purpose

To evaluate and compare 3 anti-pneumocystis regimens plus zidovudine (AZT) in persons with HIV infection and T4 cell count less than 200 cells/mm3. All persons completing at least 8 weeks of therapy on 081 will be offered the opportunity to participate in the nested study (ACTG 981) of systemic antifungal therapy (fluconazole) versus local therapy (Clotrimazole) for the prevention of serious fungal disease.

Persons with HIV disease who are receiving AZT are at risk for PCP, toxoplasmosis, bacterial pneumonia, and other serious infections. It is therefore important to find drugs that can be given along with AZT to control these infections. Aerosolized pentamidine (PEN) has been shown to be useful in preventing PCP and is expected to lower the 2-year risk of PCP. Both sulfamethoxazole/trimethoprim (SMX/TMP) and dapsone probably also provide effective preventive treatment against PCP, and both may be useful in preventing toxoplasmosis and extrapulmonary pneumocystosis.


Condition Intervention Phase
Pneumonia, Pneumocystis Carinii
HIV Infections
Drug: Pentamidine isethionate
Drug: Sulfamethoxazole-Trimethoprim
Drug: Dapsone
Drug: Zidovudine
Phase III

MedlinePlus related topics: AIDS Pneumonia Toxoplasmosis
Drug Information available for: Zidovudine Sulfamethoxazole Trimethoprim Trimethoprim-sulfamethoxazole combination Dapsone Pentamidine
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment, Open Label
Official Title: A Randomized Trial of Three Anti-Pneumocystis Agents Plus Zidovudine for the Primary Prevention of Serious Infections in Patients With Advanced HIV Infection

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

Estimated Enrollment: 600
Detailed Description:

Persons with HIV disease who are receiving AZT are at risk for PCP, toxoplasmosis, bacterial pneumonia, and other serious infections. It is therefore important to find drugs that can be given along with AZT to control these infections. Aerosolized pentamidine (PEN) has been shown to be useful in preventing PCP and is expected to lower the 2-year risk of PCP. Both sulfamethoxazole/trimethoprim (SMX/TMP) and dapsone probably also provide effective preventive treatment against PCP, and both may be useful in preventing toxoplasmosis and extrapulmonary pneumocystosis.

All patients receive AZT. In addition, they are placed in one of three groups to receive either SMX/TMP, dapsone, or PEN. Stratification criteria are:

Received first AZT equal to or less than 6 weeks prior to study entry. Received first AZT more than 6 weeks prior to study entry. Potential to participate in ACTG 981. ACTG center in which the patient is enrolled.

  Eligibility

Ages Eligible for Study:   13 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

Concurrent Medication:

Allowed:

  • Antifolate medication required to treat an intercurrent infection.
  • Treatment of intercurrent infections or malignancies.
  • Fluconazole.
  • Itraconazole.
  • Standard or investigational therapy for pneumocystosis (PCP) or toxoplasmosis.
  • Only the forms of primary prophylaxis for PCP or toxoplasmosis assigned to the participant under the protocol. Patients who develop intolerance to all forms of prophylaxis assigned in this protocol or who develop PCP or toxoplasmosis may receive alternate or investigation forms of prophylaxis with or without zidovudine but must continue to be followed under this protocol.
  • Discouraged but allowed: AL-721.
  • Chronic acyclovir.
  • Ketoconazole.
  • Amphotericin B.
  • Corticosteroids at greater than physiologic replacement doses are strongly discouraged.
  • They should be used as briefly as possible and only for definite specific indications.

Patient must conform to the following:

  • Receiving or candidates for zidovudine therapy at least 500 mg/day under current labeled indications with no history of pneumocystosis (PCP) or toxoplasmosis.
  • Evidence of HIV infection documented by HIV antibody tests.
  • T4 cell count less than 200 cells/mm3 at any time prior to study entry.
  • Willing to sign informed consent.
  • Willing to be followed by a participating ACTG center for duration of the study.
  • Allowed: Concurrent enrollment in long-term follow-up studies in previously blinded trials of AZT (ACTG 016 and 019).

Exclusion Criteria

Co-existing Condition:

Patients with the following conditions are excluded:

  • History of documented or presumed pneumocystosis (PCP) or toxoplasmosis.
  • Active bacterial or mycobacterial infection.
  • History of type I hypersensitivity, exfoliative rash, or rash with mucosal involvement, severe bronchospasm, or other life-threatening reaction to any of the study drugs or to other sulfas, sulfones, or pentamidine.
  • History of intolerance causing dose interruption while receiving zidovudine at equal to or less than 600 mg/day or causing dose reduction to less than 500 mg/day within 4 weeks prior to entry.
  • Advanced Kaposi's sarcoma or other malignancy not specifically allowed that has been rapidly progressive during the month prior to enrollment or which may be expected to require chemotherapy within 90 days of study entry.

Concurrent Medication:

Excluded:

  • Active primary treatment for an infection or malignancy.
  • Other form of antifolate medication not specifically allowed.
  • Other antiretroviral or biologic response modifier.
  • Ganciclovir, if it causes intolerance to AZT equal to or more than 500 mg/day.
  • Foscarnet.

Patients with the following are excluded:

  • Symptoms and conditions defined in Exclusion Coexisting Conditions.
  • Glucose 6-phosphate dehydrogenase deficiency (GPD).
  • History of pneumocystosis (PCP) or toxoplasmosis.
  • History of type I hypersensitivity, exfoliative rash, or rash with mucosal involvement, severe bronchospasm, or other life-threatening reaction to any of the study drugs or to other sulfas, sulfones, or pentamidine.
  • History of intolerance causing dose interruption while receiving zidovudine at equal to or less than 500 mg/day with 4 weeks pior to study entry.

Prior Medication:

Excluded within 4 weeks of study entry:

  • Any other form of pneumocystosis (PCP) chemoprophylaxis.
  • Active substance abuse, including alcohol.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00000991

  Show 40 Study Locations
Sponsors and Collaborators
Investigators
Study Chair: S Bozzette
Study Chair: S Spector
  More Information

Click here for more information about Zidovudine  This link exits the ClinicalTrials.gov site
Click here for more information about Pentamidine isethionate  This link exits the ClinicalTrials.gov site
Click here for more information about Sulfamethoxazole-Trimethoprim  This link exits the ClinicalTrials.gov site

Publications:
Bozzette SA, Hays RD, Berry SH, Kanouse DE. A Perceived Health Index for use in persons with advanced HIV disease: derivation, reliability, and validity. Med Care. 1994 Jul;32(7):716-31.
Bozzette SA, Finkelstein DM, Spector SA, Frame P, Powderly WG, He W, Phillips L, Craven D, van der Horst C, Feinberg J. A randomized trial of three antipneumocystis agents in patients with advanced human immunodeficiency virus infection. NIAID AIDS Clinical Trials Group. N Engl J Med. 1995 Mar 16;332(11):693-9.
Glick ME. CTG studies yield results. AIDS Clinical Trials Group. NIAID AIDS Agenda. 1995 Spring;:8-9. No abstract available.
Justice AC, Rabeneck L, Hays RD, Wu AW, Bozzette SA. Sensitivity, specificity, reliability, and clinical validity of provider-reported symptoms: a comparison with self-reported symptoms. Outcomes Committee of the AIDS Clinical Trials Group. J Acquir Immune Defic Syndr. 1999 Jun 1;21(2):126-33.
Justice AC, Holmes W, Gifford AL, Rabeneck L, Zackin R, Sinclair G, Weissman S, Neidig J, Marcus C, Chesney M, Cohn SE, Wu AW. Development and validation of a self-completed HIV symptom index. J Clin Epidemiol. 2001 Dec;54 Suppl 1:S77-90.
Ioannidis JP, Dixon DO, McIntosh M, Albert JM, Bozzette SA, Schnittman SM. Relationship between event rates and treatment effects in clinical site differences within multicenter trials: an example from primary Pneumocystis carinii prophylaxis. Control Clin Trials. 1999 Jun;20(3):253-66.
DiRienzo AG, van Der Horst C, Finkelstein DM, Frame P, Bozzette SA, Tashima KT. Efficacy of trimethoprim-sulfamethoxazole for the prevention of bacterial infections in a randomized prophylaxis trial of patients with advanced HIV infection. AIDS Res Hum Retroviruses. 2002 Jan 20;18(2):89-94.

Study ID Numbers: ACTG 081
Study First Received: November 2, 1999
Last Updated: August 25, 2008
ClinicalTrials.gov Identifier: NCT00000991  
Health Authority: United States: Federal Government

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Trimethoprim-Sulfamethoxazole Combination
Toxoplasmosis
AIDS-Related Opportunistic Infections
Pneumonia, Pneumocystis carinii
Pentamidine
Dapsone
Drug Evaluation
Drug Therapy, Combination
Acquired Immunodeficiency Syndrome
Zidovudine
Sulfamethoxazole-Trimethoprim

Study placed in the following topic categories:
Opportunistic Infections
Sexually Transmitted Diseases, Viral
Trimethoprim
Clotrimazole
Miconazole
Zidovudine
Trimethoprim-Sulfamethoxazole Combination
Pneumonia, Pneumocystis
Mycoses
Respiratory Tract Diseases
Respiratory Tract Infections
AIDS-Related Opportunistic Infections
Dapsone
Pentamidine
Retroviridae Infections
Lung Diseases, Fungal
Sulfamethoxazole
Acquired Immunodeficiency Syndrome
Tioconazole
Immunologic Deficiency Syndromes
Toxoplasmosis
Virus Diseases
Folic Acid
Pneumocystis Infections
HIV Infections
Lung Diseases
Sexually Transmitted Diseases
Pneumonia

Additional relevant MeSH terms:
Antimetabolites
Anti-Infective Agents
Communicable Diseases
Trypanocidal Agents
Antiprotozoal Agents
Slow Virus Diseases
Molecular Mechanisms of Pharmacological Action
Infection
Renal Agents
Reverse Transcriptase Inhibitors
Antimalarials
Anti-Bacterial Agents
Antiparasitic Agents
Anti-Retroviral Agents
Therapeutic Uses
Antifungal Agents
Nucleic Acid Synthesis Inhibitors
RNA Virus Infections
Anti-HIV Agents
Immune System Diseases
Enzyme Inhibitors
Anti-Infective Agents, Urinary
Folic Acid Antagonists
Antiviral Agents
Pharmacologic Actions
Lentivirus Infections
Leprostatic Agents

ClinicalTrials.gov processed this record on January 15, 2009