Clinical trial NCT00114933: "OK 2004 Study" (Only Kaletra 2004 Study): Study to Evaluate Suspending Nucleosides From Triple-Drug Therapy in HIV Subjects
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: HIV Infection
Keywords: HIV
AIDS
Treatment Experienced
Lead sponsor: Arribas, Jose R., M.D.
Sponsor class: INDIV
Collaborators: name: Pulido, Federico, M.D.
name: Abbott
First posted: 2005-06-21
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: % patients with therapeutic failure in both arms at 48 weeks (OT and ITT)
Secondary outcomes:
measure: % patients with virological failure: HIV-RNA > 500 cop/ml under the randomly assigned therapy (OT and ITT)
measure: % patients with HIV RNA < 500 cop/ml and < 50 cop/ml at w24, w48 (OT and ITT)
measure: Time to virological failure per Kaplan Meyer analysis
measure: CD4 cell count change from baseline
measure: Percentage of viruses with resistance in the protease gene at w24 and w48
measure: Description of AEs with probable, possible or unknown relationship to study drug
Other outcomes:
Locations:
city: Elche
country: Spain
facility: Hospital General de Elche
state: Alicante
city: Hospitalet de LLobregat
country: Spain
facility: Hospital de Bellvitge
state: Barcelona
city: Las Palmas de Gran Canaria
country: Spain
facility: Hospital Insular
state: Gran Canaria
city: San Sebastián
country: Spain
facility: Hospital de Donostia
state: Guipuzcoa
city: Alcalá de Henares
country: Spain
facility: Hospital U. Príncipe de Asturias
state: Madrid
city: Vigo
country: Spain
facility: Hospital Xeral Cies
state: Pontevedra
city: Santa Cruz de Tenerife
country: Spain
facility: Hospital Universitario de Canarias
state: Tenerife
city: Bilbao
country: Spain
facility: Hospital de Basurto
state: Vizcaya
city: Alicante
country: Spain
facility: Hospital General de Alicante
city: Barcelona
country: Spain
facility: Hospital del Mar
city: Barcelona
country: Spain
facility: Hospital Sant Creu i Sant Pau
city: Barcelona
country: Spain
facility: Hospital Clinic i Provincial
city: Barcelona
country: Spain
facility: Hospital Germans Trias i Pujol
city: Granada
country: Spain
facility: Hospital Virgen de las Nieves
city: Madrid
country: Spain
facility: Hospital La Paz
city: Madrid
country: Spain
facility: Hospital La Princesa
city: Madrid
country: Spain
facility: Hospital Gregorio Marañón
city: Madrid
country: Spain
facility: Hospital Ramón y Cajal
city: Madrid
country: Spain
facility: Fundación Jiménez Díaz
city: Madrid
country: Spain
facility: Hospital Clínico San Carlos
city: Madrid
country: Spain
facility: Hospital 12 de Octubre
city: Sevilla
country: Spain
facility: Hospital Virgen Macarena
city: Sevilla
country: Spain
facility: Hospital Nuestra Señora de Valme (Sevilla)
city: Valencia
country: Spain
facility: Hospital La Fe
city: Valencia
country: Spain
facility: Hospital Clínico de Valencia
city: Valencia
country: Spain
facility: Hospital General de Valencia
city: Valencia
country: Spain
facility: Hospital Dr. Peset
city: Zaragoza
country: Spain
facility: Hospital Miguel Servet
Study officials:
affiliation: Hospital La Paz
name: José R. Arribas, MD
role: STUDY_CHAIR
affiliation: Hospital 12 de Octubre
name: Federico Pulido, MD
role: STUDY_CHAIR
References:
citation: Arribas JR, Delgado R, Arranz A, Munoz R, Portilla J, Pasquau J, Perez-Elias MJ, Iribarren JA, Rubio R, Ocampo A, Sanchez-Conde M, Knobel H, Arazo P, Sanz J, Lopez-Aldeguer J, Montes ML, Pulido F; OK04 Study Group. Lopinavir-ritonavir monotherapy versus lopinavir-ritonavir and 2 nucleosides for maintenance therapy of HIV: 96-week analysis. J Acquir Immune Defic Syndr. 2009 Jun 1;51(2):147-52. doi: 10.1097/QAI.0b013e3181a56de5.
citation: Pulido F, Arribas JR, Delgado R, Cabrero E, Gonzalez-Garcia J, Perez-Elias MJ, Arranz A, Portilla J, Pasquau J, Iribarren JA, Rubio R, Norton M; OK04 Study Group. Lopinavir-ritonavir monotherapy versus lopinavir-ritonavir and two nucleosides for maintenance therapy of HIV. AIDS. 2008 Jan 11;22(2):F1-9. doi: 10.1097/QAD.0b013e3282f4243b.