Modification of Doses of Efavirenz According to Its Blood Concentration in HIV Patients - Full Text View

Sponsor:	Germans Trias i Pujol Hospital
Collaborator:	Fundacio Lluita Contra la SIDA
Information provided by:	Germans Trias i Pujol Hospital
ClinicalTrials.gov Identifier:	NCT00299091

Purpose

This is a study on the utility of the modification of doses of efavirenz guided by its plasma concentration (therapeutic drug monitoring) in HIV-infected patients initiating treatment with Sustiva.

Condition	Intervention	Phase
HIV	Drug: Efavirenz capsules 600 mg Drug: Efavirenz capsules 200 mg and 600 mg	Phase IV

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Safety/Efficacy Study
Official Title:	Open, Parallel and Randomised Pilot Clinical Trial to Evaluate the Utility of the Therapeutic Monitoring of Plasma Levels of Efavirenz in Hiv-Infected Patients Initiating an Antiretroviral Treatment Regimen With Sustiva

Resource links provided by NLM:

MedlinePlus related topics: AIDS

Drug Information available for: Efavirenz

U.S. FDA Resources

Further study details as provided by Germans Trias i Pujol Hospital:

Primary Outcome Measures:

The proportion of patients who need to interrupt treatment with efavirenz due to virological failure [ Time Frame: after 96 weeks of follow-up ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

The proportion of patients who need to interrupt treatment with efavirenz due to adverse side effects [ Time Frame: after 96 weeks of follow-up ] [ Designated as safety issue: Yes ]
To determine the incidence of adverse events and the toxicity profile (haemogram, AST/ALT/FA/GGT, creatinine, urea) [ Time Frame: during the 96 weeks of follow-up ] [ Designated as safety issue: Yes ]
To evaluate the proportion of patients with plasma levels of efavirenz between 1.0 and 4.0 mg/L [ Time Frame: during the 96 weeks of follow-up ] [ Designated as safety issue: No ]
To evaluate the relationship between the appearance of secondary events during treatment with efavirenz and the patients' demographic and clinical characteristics, as well the plasma concentration of efavirenz [ Time Frame: during the 96 weeks of follow-up ] [ Designated as safety issue: No ]
To evaluate the variations in CD4 and CD8 lymphocyte count [ Time Frame: during the 96 weeks of follow-up ] [ Designated as safety issue: No ]

Enrollment:	31
Study Start Date:	September 2006
Study Completion Date:	October 2008
Primary Completion Date:	October 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Control: No Intervention Efavirenz capsules 600 mg	Drug: Efavirenz capsules 600 mg Efavirenz capsules 600 mg
Experimental: Experimental Modification of doses of efavirenz guided by its plasma concentration (therapeutic drug monitoring)	Drug: Efavirenz capsules 200 mg and 600 mg Modification of doses of efavirenz guided by its plasma concentration (therapeutic drug monitoring)

Detailed Description:

Currently, efavirenz is dosed systematically, without taking into account the individual characteristics of each individual patient. However, plasma concentration of efavirenz may widely vary between different subjects that receive the same dose of the drug (interindividual variability).

Therapeutic drug monitoring (TDM) signifies individualised pharmacological dosing, based on the plasma levels that each patient presents. This strategy has been broadly used in the field of the treatment of other medical conditions and is acquiring growing interest in the field of antiretroviral treatment. Thus, the use of TDM for the treatment of naïve patients with nelfinavir or with indinavir has translated into an increase in the proportion of individuals with suppressed viral load and also into a reduction in HAART-induced adverse events . However, data on the utility of the therapeutic monitoring of the levels of efavirenz in HIV-infected patients are very scant.

On the basis of the above, it might be thought that the modification of the doses of efavirenz, guided by its plasma concentration, in patients receiving this drug and whose plasma levels of efavirenz are outside the therapeutic range, might improve the tolerability of the treatment without compromising virological efficacy.

Eligibility

Ages Eligible for Study:	18 Years to 65 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

HIV-1 patients.
According to the criteria of the treating physician, the need to initiate a regimen of antiretroviral treatment that includes efavirenz (both antiretroviral-naive patients and others on treatment with protease inhibitors switching to efavirenz for salvage reasons or for simplification of the anti-retroviral therapy are included).
Absence of opportunistic infections and/or tumours in the three months prior to inclusion.

Exclusion Criteria:

History of allergic hypersensitivity to the investigational drug.
History of previous failure with antiretroviral treatment with non-nucleoside reverse transcriptase inhibitors or previously documented resistance to efavirenz
History of psychiatric comorbidity which, in the investigator's opinion, renders the use of efavirenz inadvisable.
Active consumption of alcohol (>50 g/day) or other illegal drugs (except cannabis)
Suspicion of unsuitable compliance with the antiretroviral treatment.
Pregnant women or breast-feeding mothers.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00299091

Locations

Spain, Barcelona
Germans Trias i Pujol Hospital
Badalona, Barcelona, Spain, 08916

Sponsors and Collaborators

Germans Trias i Pujol Hospital

Fundacio Lluita Contra la SIDA

Investigators

Principal Investigator:

Bonaventura Clotet, MD, PhD

Lluita Sida Foundation-HIV Unit

More Information

No publications provided

Responsible Party:	LLuita Sida Foundation ( LLuita Sida Foundation )
Study ID Numbers:	startTDM-EFV, 2005-002493-30
Study First Received:	March 3, 2006
Last Updated:	October 14, 2008
ClinicalTrials.gov Identifier:	NCT00299091 History of Changes
Health Authority:	Spain: Ministry of Health

Keywords provided by Germans Trias i Pujol Hospital:

Therapeutic drug monitoring
Treatment Naive
Treatment Experienced
HIV

Additional relevant MeSH terms:

Anti-Infective Agents
Efavirenz
Anti-HIV Agents
Anti-Retroviral Agents
Molecular Mechanisms of Pharmacological Action
Therapeutic Uses

Enzyme Inhibitors
Antiviral Agents
Pharmacologic Actions
Nucleic Acid Synthesis Inhibitors
Reverse Transcriptase Inhibitors

ClinicalTrials.gov processed this record on February 08, 2010