"OK 2004 Study" (Only Kaletra 2004 Study): Study to Evaluate Suspending Nucleosides From Triple-Drug Therapy in HIV Subjects

Phase 4

Completed

• Conditions: HIV Infection

• Registration Number: NCT00114933
• Lead Sponsor: Arribas, Jose R., M.D.

Brief Summary

Lopinavir/ritonavir monotherapy may maintain virologic suppression in patients who have been undetectable for six months while on triple drug antiretroviral therapy. Lopinavir/ritonavir pharmacokinetics might prevent resistance development in patients who experience virological rebound after single-drug simplification.

Detailed Description

Primary Study Objective: Efficacy and durability of switching to lopinavir/ritonavir single-drug HAART compared to maintaining therapy based on lopinavir/ritonavir and two nucleosides

Secondary Study Objective(s):

* Safety (related drug AEs/SAEs and laboratory anomalies G3/4) through 48 w.

* Resistance profile on patients with sustained virological failure

* QOL comparing stopping nucleosides versus continuing therapy

* Pharmaco-economic analysis comparing treatment cost between the 2 study arms.

* Predicting factors of failure in the stopping nucleosides arm

Subject Population: 200 patients

Study Design:

RANDOMIZATION:

Patients are randomized (1:1) either to continue under the same treatment or stop nucleosides as follows:

* Stopping nucleosides arm: Lopinavir/r alone.

* Continuing arm: Lopinavir/r + 2 NRTIs

STUDY PROCEDURES: A baseline HIV-RNA, CD4 and routine labs will be collected if the most recent results are not collected within the 4 weeks prior entering the study. Patients will be followed for HIV-RNA (and CD4) at w1, w4, w8, w16, w24, w 36 and w48. After w48, durability of response to lopinavir/r single-drug therapy will be studied long-term (up to w96). Routine hematology and clinical chemistry (including fasting triglycerides and cholesterol, total and HDL/LDL ratio) will be measured at w4, w16, w24, w 36 and w48. A central laboratory will be used for HIV-RNA determinations and to archive plasma/cell samples for further genotype test in case of rebound.

Treatment adherence will be followed with a self-patient report questionnaire (GEEMA study)

All AEs will be collected if suspected relation (possible or probable) to any concomitant ARV drug, and SAEs, related or not, reported within 24h.

Study Timeline

• Study Start: 2005-01
• Study First Submitted: 2005-06-20
• Study First Submitted QC: 2005-06-20
• Study First Posted: 2005-06-21
• Status Verified: 2005-09
• Study Completion: 2007-05
• Last Update Submitted: 2008-03-20
• Last Update Posted: 2008-03-21

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 200

Inclusion Criteria

• HIV patients > 18 years old who provide signed and dated Informed consent.
• HIV patients who have been receiving lopinavir/ritonavir and two nucleosides during at least 4 weeks.
• Plasma HIV RNA < 50 cop/ml for six months

Exclusion Criteria

• HIV patients who have stopped a protease inhibitor due to virological failure.
• HIV patients with hepatic or renal insufficiency.
• HIV patients with positive serum HBVAg
• HIV patients who require treatment with a lopinavir/r contraindicated medication.
• HIV pregnant or breastfeeding women.
• Active drug abuse (including alcohol or recreational drugs). Exception, cannabis, provided the investigator is confident in patient adherence. Patients under Methadone program will be accepted too if deemed appropriate by the investigator.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
% patients with therapeutic failure in both arms at 48 weeks (OT and ITT)

Secondary Outcome Measures

Name	Time	Method
% patients with virological failure: HIV-RNA > 500 cop/ml under the randomly assigned therapy (OT and ITT)
% patients with HIV RNA < 500 cop/ml and < 50 cop/ml at w24, w48 (OT and ITT)
Time to virological failure per Kaplan Meyer analysis
CD4 cell count change from baseline
Percentage of viruses with resistance in the protease gene at w24 and w48
Description of AEs with probable, possible or unknown relationship to study drug

Trial Locations

Locations (28)

Hospital de Bellvitge; 🇪🇸 Hospitalet de LLobregat, Barcelona, Spain

Hospital Universitario de Canarias; 🇪🇸 Santa Cruz de Tenerife, Tenerife, Spain

Hospital Sant Creu i Sant Pau; 🇪🇸 Barcelona, Spain

Hospital Clinic i Provincial; 🇪🇸 Barcelona, Spain

Hospital Germans Trias i Pujol; 🇪🇸 Barcelona, Spain

Hospital de Basurto; 🇪🇸 Bilbao, Vizcaya, Spain

Hospital del Mar; 🇪🇸 Barcelona, Spain

Hospital General de Alicante; 🇪🇸 Alicante, Spain

Hospital Nuestra Señora de Valme (Sevilla); 🇪🇸 Sevilla, Spain

Hospital Dr. Peset; 🇪🇸 Valencia, Spain

Hospital Miguel Servet; 🇪🇸 Zaragoza, Spain

Hospital La Fe; 🇪🇸 Valencia, Spain

Hospital General de Valencia; 🇪🇸 Valencia, Spain

Hospital General de Elche; 🇪🇸 Elche, Alicante, Spain

Hospital Insular; 🇪🇸 Las Palmas de Gran Canaria, Gran Canaria, Spain

Hospital U. Príncipe de Asturias; 🇪🇸 Alcalá de Henares, Madrid, Spain

Hospital de Donostia; 🇪🇸 San Sebastián, Guipuzcoa, Spain

Hospital Xeral Cies; 🇪🇸 Vigo, Pontevedra, Spain

Hospital La Paz; 🇪🇸 Madrid, Spain

Hospital La Princesa; 🇪🇸 Madrid, Spain

Hospital Ramón y Cajal; 🇪🇸 Madrid, Spain

Hospital Gregorio Marañón; 🇪🇸 Madrid, Spain

Hospital Virgen Macarena; 🇪🇸 Sevilla, Spain

Hospital 12 de Octubre; 🇪🇸 Madrid, Spain

Hospital Virgen de las Nieves; 🇪🇸 Granada, Spain

Hospital Clínico San Carlos; 🇪🇸 Madrid, Spain

Fundación Jiménez Díaz; 🇪🇸 Madrid, Spain

Hospital Clínico de Valencia; 🇪🇸 Valencia, Spain