Adjusting Antiretroviral Therapy Dosage Using Therapeutic Drug Monitoring

HIV Infections Clinical Trial

— TDM  

Official title:

Adjusting Antiretroviral Therapy Dosage Using Therapeutic Drug Monitoring

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT00836212
• Other study ID #: SHCS 571
• Status: Recruiting
• Phase: Phase 4
• First received: February 3, 2009
• Last updated: July 21, 2009
• Start date: March 2008
• Est. completion date: April 2009

Study information

• Verified date: July 2009
• Source: University Hospital, Geneva
• Contact: Alexnadra AC Calmy
• Phone: 022 372 98 08
• Email: Alexandra.Calmy[@]hcuge.ch
• Is FDA regulated: No
• Health authority: Switzerland: Swissmedic
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 12
• Est. completion date: April 2009
• Est. primary completion date: April 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

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

Related Conditions & MeSH terms

• Acquired Immunodeficiency Syndrome
• HIV Infections
• Human Immunodeficiency Virus
• Immunologic Deficiency Syndromes

Intervention

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.
• 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.

Locations

Country	Name	City	State
Switzerland	University Hopistal of Geneva	Geneva

Sponsors (2)

Lead Sponsor	Collaborator
University Hospital, Geneva	Swiss HIV Cohort Study

Country where clinical trial is conducted

Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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		6 months	No
Secondary	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		6 months	No

External Links

•   Profil of Alexandra Calmy
•   Profil of Professor Bernard Hirschel
•   Swiss HIV Cohort Study