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Adjusting Antiretroviral Therapy Dosage Using Therapeutic Drug Monitoring (TDM)

The recruitment status of this study is unknown because the information has not been verified recently.
Verified July 2009 by University Hospital, Geneva.
Recruitment status was  Recruiting
Sponsor:
Collaborator:
Swiss HIV Cohort Study
Information provided by:
University Hospital, Geneva
ClinicalTrials.gov Identifier:
NCT00836212
First received: February 3, 2009
Last updated: July 21, 2009
Last verified: July 2009
  Purpose

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.


Condition Intervention Phase
Human Immunodeficiency Virus
HIV Infections
Drug: Reducing dose of Lopinavir
Drug: Reducing dose of efavirenz
Phase 4

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Adjusting Antiretroviral Therapy Dosage Using Therapeutic Drug Monitoring

Resource links provided by NLM:


Further study details as provided by University Hospital, Geneva:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

Estimated Enrollment: 12
Study Start Date: March 2008
Estimated Study Completion Date: April 2009
Estimated Primary Completion Date: April 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
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.
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.
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  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: NCT00836212

Contacts
Contact: Alexnadra AC Calmy 022 372 98 08 ext +41 Alexandra.Calmy@hcuge.ch

Locations
Switzerland
University Hopistal of Geneva Recruiting
Geneva, Switzerland, 1211
Contact: Alexandra AC Calmy, MD    022 372 98 08 ext +41    Alexandra.Calmy@hcuge.ch   
Principal Investigator: Bernard BH Hirschel, MD         
Principal Investigator: Alexandra AC Calmy, MD         
Sponsors and Collaborators
University Hospital, Geneva
Swiss HIV Cohort Study
Investigators
Principal Investigator: Alexandra AC Calmy University Hospital, Geneva
  More Information

Additional Information:
No publications provided

Responsible Party: Alexandra Calmy / Doctor, University Hospital, Geneva
ClinicalTrials.gov Identifier: NCT00836212     History of Changes
Other Study ID Numbers: SHCS 571
Study First Received: February 3, 2009
Last Updated: July 21, 2009
Health Authority: Switzerland: Swissmedic

Keywords provided by University Hospital, Geneva:
HIV
Adjusting Antiretroviral Therapy
Dosage using Therapeutic Drug Monitoring
Swiss HIV Cohort Study
HIV Geneva
lopinavir
efavirenz
Treatment Experienced

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
HIV Infections
Immunologic Deficiency Syndromes
Immune System Diseases
Lentivirus Infections
RNA Virus Infections
Retroviridae Infections
Sexually Transmitted Diseases
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Virus Diseases
Efavirenz
Lopinavir
Anti-HIV Agents
Anti-Infective Agents
Anti-Retroviral Agents
Antiviral Agents
Enzyme Inhibitors
HIV Protease Inhibitors
Molecular Mechanisms of Pharmacological Action
Nucleic Acid Synthesis Inhibitors
Pharmacologic Actions
Protease Inhibitors
Reverse Transcriptase Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on November 25, 2014