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

History of Changes

Tracking Information

First Received Date ^ICMJE

February 3, 2009

Last Updated Date

July 21, 2009

Start Date ^ICMJE

March 2008

Estimated Primary Completion Date

April 2009 (final data collection date for primary outcome measure)

Current Primary Outcome Measures ^ICMJE

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 ]

Original Primary Outcome Measures ^ICMJE

Same as current

Change History

Complete list of historical versions of study NCT00836212 on ClinicalTrials.gov Archive Site

Current Secondary Outcome Measures ^ICMJE

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 ]

Original Secondary Outcome Measures ^ICMJE

Same as current

Current Other Outcome Measures ^ICMJE

Not Provided

Original Other Outcome Measures ^ICMJE

Not Provided

Descriptive Information

Brief Title ^ICMJE

Adjusting Antiretroviral Therapy Dosage Using Therapeutic Drug Monitoring

Official Title ^ICMJE

Adjusting Antiretroviral Therapy Dosage Using Therapeutic Drug Monitoring

Brief Summary

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.

Detailed Description

Not Provided

Study Type ^ICMJE

Interventional

Study Phase

Phase 4

Study Design ^ICMJE

Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment

Condition ^ICMJE

Human Immunodeficiency Virus
HIV Infections

Intervention ^ICMJE

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.

Study Arm (s)

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

Publications *

Not Provided

* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.

Recruitment Information

Recruitment Status ^ICMJE

Recruiting

Estimated Enrollment ^ICMJE

Estimated Completion Date

April 2009

Estimated Primary Completion Date

April 2009 (final data collection date for primary outcome measure)

Eligibility Criteria ^ICMJE

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

Gender

Both

Ages

18 Years and older

Accepts Healthy Volunteers

Contacts ^ICMJE

Contact: Alexnadra AC Calmy

022 372 98 08 ext +41

Alexandra.Calmy@hcuge.ch

Location Countries ^ICMJE

Switzerland

Administrative Information

NCT Number ^ICMJE

NCT00836212

Other Study ID Numbers ^ICMJE

SHCS 571

Has Data Monitoring Committee

Not Provided

Responsible Party

Alexandra Calmy / Doctor, University Hospital, Geneva

Study Sponsor ^ICMJE

University Hospital, Geneva

Collaborators ^ICMJE

Swiss HIV Cohort Study

Investigators ^ICMJE

Principal Investigator:

Alexandra AC Calmy

University Hospital, Geneva

Information Provided By

University Hospital, Geneva

Verification Date

July 2009

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

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