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Adjusting Antiretroviral Therapy Dosage Using Therapeutic Drug Monitoring (TDM)

The recruitment status of this study is unknown. The completion date has passed and the status has not been verified in more than two years.
Verified July 2009 by University Hospital, Geneva.
Recruitment status was:  Recruiting
Sponsor:
ClinicalTrials.gov Identifier:
NCT00836212
First Posted: February 4, 2009
Last Update Posted: July 23, 2009
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborator:
Swiss HIV Cohort Study
Information provided by:
University Hospital, Geneva
February 3, 2009
February 4, 2009
July 23, 2009
March 2008
April 2009   (Final data collection date for primary outcome measure)
Number of patients who reach a plasma concentration within targets (P25-P75) after at least one cycle (and maximum two cycles) of dose reduction according to the provided algorithm at 6 months [ Time Frame: 6 months ]
Same as current
Complete list of historical versions of study NCT00836212 on ClinicalTrials.gov Archive Site
Number of patients who reach a plasma concentration within targets (P25-P75) after at least one cycle of dose reduction -percentage of spared drugs through TDM-guided dosage adaptation over a 6 months period. Compliance: electronic pills count [ Time Frame: 6 months ]
Same as current
Not Provided
Not Provided
 
Adjusting Antiretroviral Therapy Dosage Using Therapeutic Drug Monitoring
Adjusting Antiretroviral Therapy Dosage Using Therapeutic Drug Monitoring

Background

Low concentrations of protease inhibitors (PIs) or nonnucleoside reverse transcriptase inhibitors (NNRTIs) are associated with an increased risk of virological failure. Likewise, excessive antiretroviral drug concentrations increase the risk of toxicity. Therapeutic drug monitoring (TDM) may identify and correct excessively high or low PI and/or NNRTI concentrations, and thus minimize toxicity and risk of treatment failure. Treatment guidelines only recommend using TDM to help optimize ARV therapy in selected patients, and there are no clear recommendations to guide the clinician who decides to adjust drug doses. Prospective studies have demonstrated the relationship between EFV plasma concentration and neuropsychiatric symptoms. Moreover, EFV is metabolized mainly by cytochrome P450 2B6 and its concentration was reported to be associated with the CYP2B6 516GrT genetic polymorphism.

For drugs such as EFV or LPV/r, lower doses than the ones validated for standard clinical use have demonstrated efficacy in dose-ranging studies.

The investigators will use a standardised algorithm to reduce doses in patients with plasma EFV or LPV/r concentration above percentile 75. This algorithm is based on a Bayesian approach from the pharmacology unit in Lausanne. The investigators hypothesize that a dosage individualisation is feasible and safe.

2.2 Study Aims

The investigators aim at testing a simplified algorithm for dose reduction in patients with documented virological efficacy, treated by a stable LPV/r or EFV based regimen with elevated plasma concentration of these drugs.

Study Design

Prospective open label study in which all eligible patients screened with a plasma drug concentration of either EFV or LPV/r above percentile 75 will be included. After confirmation of the results at baseline, patients will be offered to decrease drug dosage by a third or a half according to a standardised algorithm. All patients will undergo HIVRNA, biochemistry and validated questionnaires after 3 and 6 months to assess the safety and the benefit of this strategy.

Not Provided
Interventional
Phase 4
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
  • Human Immunodeficiency Virus
  • HIV Infections
  • Drug: Reducing dose of Lopinavir
    Patients with blood levels measured 2 times at 2 weeks intervals in the upper quartile (>percentile 75) of concentrations reported under standard therapy (i.e. EFV 600 mg q.d. or LPV/r 400 or 533 mg bid) will have their dose reduced by approximately one third, with the aim to bring their concentration in the 25-75% percentile range.
  • Drug: Reducing dose of efavirenz
    Patients with blood levels measured 2 times at 2 weeks intervals in the upper quartile (>percentile 75) of concentrations reported under standard therapy (i.e. EFV 600 mg q.d. or LPV/r 400 or 533 mg bid) will have their dose reduced by approximately one third, with the aim to bring their concentration in the 25-75% percentile range.
  • Experimental: LPV
    Patients with blood levels measured 2 times at 2 weeks intervals in the upper quartile (>percentile 75) of concentrations reported under standard therapy (i.e. EFV 600 mg q.d. or LPV/r 400 or 533 mg bid) will have their dose reduced by approximately one third, with the aim to bring their concentration in the 25-75% percentile range.
    Intervention: Drug: Reducing dose of Lopinavir
  • Experimental: EFV
    Patients with blood levels measured 2 times at 2 weeks intervals in the upper quartile (>percentile 75) of concentrations reported under standard therapy (i.e. EFV 600 mg q.d. or LPV/r 400 or 533 mg bid) will have their dose reduced by approximately one third, with the aim to bring their concentration in the 25-75% percentile range.
    Intervention: Drug: Reducing dose of efavirenz
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Unknown status
12
April 2009
April 2009   (Final data collection date for primary outcome measure)

Inclusion Criteria:

  • Stable regimen including either EFV or LPV/r
  • HIVRNA below 40 copies since at least 3 months
  • Antiretroviral drug concentration (EFV, LPV/r) plasma concentration at screening above P75
  • Signed consent for the SHCS genetics core project

Exclusion Criteria:

  • Concomitant medication:Amiodarone, bepidril, flecainide, propafenone, quinidine,Astemizole, terfenadine,Dihydroergotamine, ergotamine,Midazolam, triazolam,Cisapride,Pimozide,Rifabutin
  • Renal or hepatic impairment
  • Pregnancy or wish to become pregnant within the next 6 months
  • Both EFV and LPV/r as part of the antiretroviral drug regimen
Sexes Eligible for Study: All
18 Years and older   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
Switzerland
 
 
NCT00836212
SHCS 571
Not Provided
Not Provided
Not Provided
Alexandra Calmy / Doctor, University Hospital, Geneva
University Hospital, Geneva
Swiss HIV Cohort Study
Principal Investigator: Alexandra AC Calmy University Hospital, Geneva
University Hospital, Geneva
July 2009

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