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

Sponsor

Arribas, Jose R., M.D. (Other)

Overall Status

Completed

CT.gov ID

NCT00114933

Collaborator

Pulido, Federico, M.D. (Other), Abbott (Industry)

200

Enrollment

Locations

27.9

Duration (Months)

7.1

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
HIV Infection	Drug: Stopping nucleosides and continuing lopinavir/ritonavir monotherapy	Phase 4

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 Design

Study Type:

Interventional

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Study Start Date :

Jan 1, 2005

Study Completion Date :

May 1, 2007

Outcome Measures

Primary Outcome Measures

% patients with therapeutic failure in both arms at 48 weeks (OT and ITT) []

Secondary Outcome Measures

% 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 []

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Hospital General de Elche	Elche	Alicante	Spain	03202
2	Hospital de Bellvitge	Hospitalet de LLobregat	Barcelona	Spain	08907
3	Hospital Insular	Las Palmas de Gran Canaria	Gran Canaria	Spain	35500
4	Hospital de Donostia	San Sebastián	Guipuzcoa	Spain	20014
5	Hospital U. Príncipe de Asturias	Alcalá de Henares	Madrid	Spain	28880
6	Hospital Xeral Cies	Vigo	Pontevedra	Spain	362004
7	Hospital Universitario de Canarias	Santa Cruz de Tenerife	Tenerife	Spain	38010
8	Hospital de Basurto	Bilbao	Vizcaya	Spain	48013
9	Hospital General de Alicante	Alicante		Spain	03010
10	Hospital del Mar	Barcelona		Spain	08003
11	Hospital Sant Creu i Sant Pau	Barcelona		Spain	08025
12	Hospital Clinic i Provincial	Barcelona		Spain	08036
13	Hospital Germans Trias i Pujol	Barcelona		Spain	08916
14	Hospital Virgen de las Nieves	Granada		Spain	18014
15	Hospital La Paz	Madrid		Spain	28 046
16	Hospital La Princesa	Madrid		Spain	28006
17	Hospital Gregorio Marañón	Madrid		Spain	28007
18	Hospital Ramón y Cajal	Madrid		Spain	28034
19	Fundación Jiménez Díaz	Madrid		Spain	28040
20	Hospital Clínico San Carlos	Madrid		Spain	28040
21	Hospital 12 de Octubre	Madrid		Spain	28041
22	Hospital Virgen Macarena	Sevilla		Spain	41009
23	Hospital Nuestra Señora de Valme (Sevilla)	Sevilla		Spain	41014
24	Hospital La Fe	Valencia		Spain	46009
25	Hospital Clínico de Valencia	Valencia		Spain	46010
26	Hospital General de Valencia	Valencia		Spain	46014
27	Hospital Dr. Peset	Valencia		Spain	46017
28	Hospital Miguel Servet	Zaragoza		Spain	50010