Clinical trial NCT00274001: Quality of Life and Changes in Metabolism of Lipids and Glucose After Switching to a Nevirapine-based Regimen in HIV+ Patients
Official title: An Open, Randomised, Multicentre, Comparative Trial, to Evaluate the Benefit of Switching From a PI-based Regimen to a Nevirapine-based Regimen on the Quality of Life, Patient Adherence, Patient's Perception of Fat Redistribution and Metabolic Changes, in HIV+ Patients Suffering From Fat Abnormalities
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: HIV Infections
Quality of Life
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2006-01-10
Enrollment: 158
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: DIAGNOSTIC

Brief summary: The purpose of this trial is to compare the effect of switching to nevirapine (Viramune®)-containing regimen on quality of life of patients with fat abnormalities and virological control whilst receiving a PI-based regimen.

Detailed description: Patients will receive one of the current standard of care regimens for the treatment of HIV infection, i.e. nevirapine (Viramune®) must be administered in conjunction with 2NRTIs, as prescribed by the investigator at the study sites. Patients randomized to the nevirapine (Viramune®)-arm of the study will receive 1x200mg tablet once daily for the first 14 days ("lead in" period) and 1x200 mg tablet twice daily at appropriately spaced intervals subsequently, plus their SOC combination of 2NRTIs as prescribed by the investigators (without changing their prior NRTIs). Patients randomized to continue their standard treatment will receive it as prescribed by the investigators. No dose modification of the study drugs is permitted during the trial. The study drug will be dispensed at randomization and every four weeks thereafter until completion of 48 weeks. After 6 months at least of treatment the switch from PI regimen to NVP regimen will be allowed to all patients included in the PI arm according to patient's willingness. In these patients AST and ALT should be checked at time 0 (switch) and every 2 weeks for 2 months.

Study Hypothesis:

Between treatment comparison of Nevirapine-based regimen versus PI-based regimen will be based on a null hypothesis of no treatment difference. The null hypothesis will be no difference between the two arms at week 24 (month 6th), against the alternative hypothesis that the mean change in physical domain of the QoL will be 10 points score (SD=20) and the difference between triglycerides normalized patients will be 20%.

Comparison(s):

The primary analysis on physical domain of QoL will be performed on the changes between last observation carried forward following the LCOF approach (i.e. visit 6 or in case of premature discontinuation visit 5 or 4) and baseline (visit 2) value using fixed-effects ANCOVA model with center and treatment groups as factors and baseline value and MMA type interaction will be also included in the main model.

Eligibility criteria: Main Inclusion criteria:

* Subject suffering with clinically evident fat redistribution including the lipodystrophic syndrome and/or with abnormal values of triglycerides, cholesterol and/or insulin resistance
* Subject on treatment with HAART including PIs for at least 9 months, without therapeutic changes for at least 6 months
* Baseline CD4+ \>200 cells/mm3
* HIV-1 RNA levels \<200 copies/mL at baseline and during the previous 6 months

Main Exclusion criteria:

* Subject with other serious or chronic disease unrelated to HIV
* Subject with active invasive infections
* Subject with Karnofsky score less than 50
* Prior NNRTs experience
* Documented or suspected acute hepatitis within 30 days prior to baseline visit, irrespective of AST and ALT values that are \>5 ULN
* Subject receiving hypolipidemic and/or antidiabetic drugs at study entry
* Subjects with central nervous system disease or pre-existing mental disturbance
* Subjects on methadone chronic treatment at study entry

Primary outcomes:
measure: Quality of Life (WHOQoL questionnaire)
timeFrame: up to 48 weeks
measure: Change in triglycerides in plasma
timeFrame: up to 48 weeks
Secondary outcomes:
measure: Patients perception of fat redistribution
timeFrame: up to 48 weeks
measure: Adherence to therapy
timeFrame: up to 48 weeks
measure: Changes in metabolism of lipids and glucose
timeFrame: up to 48 weeks
measure: Bone mineral loss
timeFrame: up to 48 weeks
measure: Therapeutic drug levels of antiretrovirals (drug plasma level / IC90)
timeFrame: up to 48 weeks
measure: Concentration of antiretrovirals in semen and vaginal secretions
timeFrame: up to 48 weeks
measure: Viral load
timeFrame: up to 48 weeks
measure: Immunological status
timeFrame: up to 48 weeks
measure: Incidence and intensity of clinical and adverse events
timeFrame: up to 48 weeks
Other outcomes:
Locations:
city: Ancona
country: Italy
facility: Ospedale Regionale
city: Antella (fi)
country: Italy
facility: Ospedale Santa Maria Annunziata
city: Bari
country: Italy
facility: Clinica di Malattie Infettive
city: Bergamo
country: Italy
facility: Ospedali Riuniti di Bergamo
city: Biella
country: Italy
facility: Ospedale degli Infermi di Biella
city: Bologna
country: Italy
facility: Istituto di Malattie Infettive
city: Brescia
country: Italy
facility: Ospedale Civile
city: Brescia
country: Italy
facility: Spedali Civili di Brescia
city: Busto Arsizio (va)
country: Italy
facility: Ospedale di Circolo di Busto
city: Cagliari
country: Italy
facility: Ospedale SS. Trinità
city: Ferrara
country: Italy
facility: Azienda Ospedaliera Arcispedale S. Anna
city: Genova
country: Italy
facility: Ospedale San Martino
city: Lecco
country: Italy
facility: Presidio Ospedaliero "A. Manzoni"
city: Mantova
country: Italy
facility: Azienda Ospedaliera Carlo Poma
city: Milano
country: Italy
facility: Ospedale Luigi Sacco
city: Milano
country: Italy
facility: Fondazione Centro S. Raffaele del Monte Tabor
city: Milano
country: Italy
facility: Azienda Ospedaliera "Luigi Sacco"
city: Milano
country: Italy
facility: Ospedale Luigi Sacco
city: Modena
country: Italy
facility: Policlinico Universitario
city: Napoli
country: Italy
facility: Ospedale A. Cotugno
city: Padova
country: Italy
facility: Azienda Ospedaliera di Padova
city: Pavia
country: Italy
facility: IRCCS Policlinico San Matteo
city: Piacenza
country: Italy
facility: Ospedale Civile
city: Pisa
country: Italy
facility: Ospedale Cisanello
Study officials:
affiliation: BI Italy
name: Boehringer Ingelheim Study Coordinator
role: STUDY_CHAIR
References: