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

HIV Infection Clinical Trial

Official title:

Phase III-IV, Comparative, Randomized, Open-Label, Study to Evaluate Safety and Efficacy of Suspending Nucleosides From a Triple-Drug Therapy Based on Lopinavir/Ritonavir Versus Continuing Triple-Drug Therapy in HIV-Infected Subjects With Undetectable Plasma HIV Viremia for Six Months

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00114933
• Other study ID #: SPA-378-05-40
• Secondary ID: EudraCT 2004-001
• Status: Completed
• Phase: Phase 4
• First received: June 20, 2005
• Last updated: March 20, 2008
• Start date: January 2005
• Est. completion date: May 2007

Study information

• Verified date: September 2005
• Source: Arribas, Jose R., M.D.
• Contact: n/a
• Is FDA regulated: No
• Health authority: Spain: Spanish Agency of Medicines
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 200
• Est. completion date: May 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

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

Related Conditions & MeSH terms

• HIV Infection

Intervention

Drug:
• Stopping nucleosides and continuing lopinavir/ritonavir monotherapy

Locations

Country	Name	City	State
Spain	Hospital U. Príncipe de Asturias	Alcalá de Henares	Madrid
Spain	Hospital General de Alicante	Alicante
Spain	Hospital Clinic i Provincial	Barcelona
Spain	Hospital del Mar	Barcelona
Spain	Hospital Germans Trias i Pujol	Barcelona
Spain	Hospital Sant Creu i Sant Pau	Barcelona
Spain	Hospital de Basurto	Bilbao	Vizcaya
Spain	Hospital General de Elche	Elche	Alicante
Spain	Hospital Virgen de las Nieves	Granada
Spain	Hospital de Bellvitge	Hospitalet de LLobregat	Barcelona
Spain	Hospital Insular	Las Palmas de Gran Canaria	Gran Canaria
Spain	Fundación Jiménez Díaz	Madrid
Spain	Hospital 12 de Octubre	Madrid
Spain	Hospital Clínico San Carlos	Madrid
Spain	Hospital Gregorio Marañón	Madrid
Spain	Hospital La Paz	Madrid
Spain	Hospital La Princesa	Madrid
Spain	Hospital Ramón y Cajal	Madrid
Spain	Hospital de Donostia	San Sebastián	Guipuzcoa
Spain	Hospital Universitario de Canarias	Santa Cruz de Tenerife	Tenerife
Spain	Hospital Nuestra Señora de Valme (Sevilla)	Sevilla
Spain	Hospital Virgen Macarena	Sevilla
Spain	Hospital Clínico de Valencia	Valencia
Spain	Hospital Dr. Peset	Valencia
Spain	Hospital General de Valencia	Valencia
Spain	Hospital La Fe	Valencia
Spain	Hospital Xeral Cies	Vigo	Pontevedra
Spain	Hospital Miguel Servet	Zaragoza

Sponsors (3)

Lead Sponsor	Collaborator
Arribas, Jose R., M.D.	Abbott, Pulido, Federico, M.D.

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	% patients with therapeutic failure in both arms at 48 weeks (OT and ITT)
Secondary	% patients with virological failure: HIV-RNA > 500 cop/ml under the randomly assigned therapy (OT and ITT)
Secondary	% patients with HIV RNA < 500 cop/ml and < 50 cop/ml at w24, w48 (OT and ITT)
Secondary	Time to virological failure per Kaplan Meyer analysis
Secondary	CD4 cell count change from baseline
Secondary	Percentage of viruses with resistance in the protease gene at w24 and w48
Secondary	Description of AEs with probable, possible or unknown relationship to study drug