Safety and Durability ofTenofovir and a Cell Cycle Agent for Viral Suppression (HADIT)

This study has been completed.
Sponsor:
Information provided by:
University of Maryland
ClinicalTrials.gov Identifier:
NCT00344981
First received: June 23, 2006
Last updated: May 21, 2010
Last verified: May 2010

June 23, 2006
May 21, 2010
June 2003
November 2006   (final data collection date for primary outcome measure)
Loss of viral suppression during maintenance therapy, defined by 3 consecutive viral load measurements greater than 50c/ml over a 48- week period. [ Time Frame: At any point during the 48 week study ] [ Designated as safety issue: Yes ]
Viral load measurements will be done throughout the study to monitor for viral suppression
  • Loss of viral suppression during maintenance therapy, defined by 3 consecutive viral load measurements greater than 50c/ml over a 48- week period.
  • Secondary Endpoints:
Complete list of historical versions of study NCT00344981 on ClinicalTrials.gov Archive Site
Laboratory Abnormalities: Routine measurements of hematology, serum chemistry, CD4 cell count, lipid profiles, and HIV-1 viral load will be performed. Viral genotypes will be performed with failure to maintain viral suppression. [ Time Frame: Throughout the 48 week study ] [ Designated as safety issue: Yes ]
These tests will be done to monitor Safety and tolerability
  • 1. Safety and Tolerability
  • Laboratory Abnormalities: Routine measurements of hematology, serum chemistry, CD4 cell count, lipid profiles, and HIV-1 viral load will be performed. Viral genotypes will be performed with failure to maintain viral suppression.
Not Provided
Not Provided
 
Safety and Durability ofTenofovir and a Cell Cycle Agent for Viral Suppression
A Study to Probe The Safety And Durability of Tenofovir And a Cell Cycle Agent to Maintain Viral Suppression

Study Hypothesis Evaluation of the durability of the combination Tenofovir and Hydroxyurea to maintain viral suppression below 50 copies/ml in volunteers who have achieved viral suppression on a standard HAART regimen.

This is a 48 week open-label, randomized study comparing the safety and durability of a highly active de-intensified therapy (Tenofovir/Hydroxyurea) to a simplified standard of care therapy (Tenofovir plus 3TC or Emtriva plus Sustiva or Nevirapine) to maintain a durable viral suppression.

Up to 20 subjects with chronic HIV-1 infection, suppressed on highly active antiretroviral therapy, and without evidence of viral resistance will be enrolled in this study. Their present HAART therapy will be stopped.

Half of the 20 volunteers will be randomized to the Tenofovir 300 mg qd/Hydroxyurea 500mg qd arm and those subjects will have Hydroxyurea added to their current screening regimen for 4 weeks prior to de-intensifying to Hydroxyurea and Tenofovir. The other half will be randomized to Sustiva 600 mg qd or Nevirapine 200 mg twice a day); Tenofovir 300 mg qd, 3TC 300 mg qd or Emtriva 200 mg once a day. Volunteers will continue on this regimen for 48 weeks. Patients will be monitored for immunological and virological parameters as well as the incidence of toxicity and side effects during the study. If a patient's viral load reaches >400 copies/ml on 3 consecutive measurements over a 6 week period, they will be terminated from the study and started back on their HAART.

Interventional
Not Provided
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
  • HIV Infections
  • AIDS
  • Drug: Tenofovir
    Half of the 20 volunteers will be randomized to the Tenofovir 300 mg qd/Hydroxyurea 500mg qd arm and those subjects will have Hydroxyurea added to their current screening regimen for 4 weeks prior to de-intensifying to Hydroxyurea and Tenofovir.
    Other Name: Viread
  • Drug: Hydroxyurea
    Half of the 20 volunteers will be randomized to the Tenofovir 300 mg qd/Hydroxyurea 500mg qd arm and those subjects will have Hydroxyurea added to their current screening regimen for 4 weeks prior to de-intensifying to Hydroxyurea and Tenofovir. Volunteers will continue on this regimen for 48 weeks. Patients will be monitored for immunological and virological parameters as well as the incidence of toxicity and side effects during the study. If a patient's viral load reaches >400 copies/ml on 3 consecutive measurements over a 6 week period, they will be terminated from the study and started back on their HAART.
    Other Name: Hydrea
Not Provided
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
9
November 2006
November 2006   (final data collection date for primary outcome measure)

Inclusion Criteria:

  1. Diagnosis of HIV infection based on western blot testing, ELISA, or HIV viral load
  2. Age greater than or equal to 18 years
  3. CD4 count greater than or equal to 200c/ml.
  4. On a standard HAART regimen of 2 or 3 nucleoside reverse transcriptase inhibitors and either a protease inhibitor or a nonnucleoside reverse transcriptase inhibitor or 3 nucleoside reverse transcriptase inhibitors (2-3NRTI's + PI or 2-3NRTI's +NNRTI or 3NRTI's).
  5. On stable, continuous HAART regimen for greater than or equal to 3 months,
  6. Viral load less than or equal to 400c/ml on all measurements in the preceding 6 months with at least 2 measurements (screening viral load can be included if needed)
  7. Viral load less than or equal to 50c/ml at screening
  8. Subject able to comply with the study protocol
  9. Signed informed consent
  10. No history of antiretroviral failure that is suspected to be from or resulted in antiretroviral resistance.

Exclusion Criteria:

  1. Serious HIV related or non HIV related carcinoma requiring chemotherapy
  2. Recent serious opportunistic infection, such as progressive multifocal leukoencephalopathy, CMV disease, cryptococcus meningitis, cerebral toxoplasmosis, but not excluding other infections in which successful treatment may be judged to be placed at risk if antiretroviral therapy was de intensified.
  3. Known or suspected intolerance or hypersensitivity to Hydroxyurea
  4. Grade 3 or higher neutropenia (using ACTG grading table)
  5. Grade 2 or higher thrombocytopenia (using ACTG grading table)
  6. Grade 2 or higher LFT abnormalities (using ACTG grading table)
  7. History of pancreatitis, or risk factors associated with pancreatitis (more then two drinks containing alcohol/day, triglyceride levels greater than 400, and pancreatic enzymes greater then 1.5x normal)
  8. Renal insufficiency (Estimated Creatinine clearance of <60ml/min.)
  9. Chronic diarrhea
  10. Pregnancy or breastfeeding
  11. Unwillingness to use effective barrier contraception or abstinence
  12. The use of systemic corticosteroids, or other systemic immunosuppressive medications; the use of cholestyramine; the use of probenecid or other inhibitors of renal tubular secretion
  13. Genotypic or phenotypic testing documenting major resistance to any antiretroviral agents
  14. Active substance or mental health concerns that are judged to place a significant limitation on medication adherence.
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00344981
H-22407
Yes
Dr. Robert R. Redfield, Institute of Human Virology
University of Maryland
Not Provided
Principal Investigator: Robert R. Redfield, MD University of Maryland, School of Medcine, Department of Infectious Disease
University of Maryland
May 2010

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