Clinical trial NCT00338390: Study to Evaluate Changes in CD4 on Replacing TDF With ABC or DDI+TDF With ABC+3TC
Official title: Study of Changes in CD4 Lymphocyte Count in Patients With a HAART Regimen Including DDI + Tenofovir and With Viral Suppression Following the Replacement of Tenofovir With Abacavir Once Daily or Following the Double Replacement of DDI + Tenofovir With Abacavir + Lamivudine in a Single Tablet
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: HIV Infections
Keywords: Antiretrovirals
CD4 cell count
toxicity
Lead sponsor: Hospital de Granollers
Sponsor class: OTHER
First posted: 2006-06-20
Enrollment: 75
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The study aims to ascertain whether the sole replacement of tenofovir with abacavir once a day improves the immunological response obtained with tenofovir + ddI or whether it is better to perform a double replacement of tenofovir and ddI with abacavir + lamivudine (joint formulation) in a single daily dose to achieve these objectives.

Detailed description: Different works have shown a high rate of virological failure among patients on abacavir + lamivudine + tenofovir or ddI + 3TC + tenofovir, thus rendering the use of these combinations actively unadvisable.

Furthermore, recent studies have also shown that ABC+3TC are associated with a significantly higher increase in CD4 than the current treatment standard formed by AZT+3TC. This provides us with grounds to suppose that patients with TDF+ddI may recover their CD4 with ABC+3HT. Similarly, and recently, the existence of pharmacokinetic interactions between tenofovir + abacavir has begun to be questioned.

Finally, the replacement of tenofovir with abacavir or tenofovir + ddI with abacavir + lamivudine does not detract from the potency of HAART, the toxicity profile is different and their behaviour at mitochondrial level is similar.

This study aims to ascertain whether the sole replacement of tenofovir with abacavir once a day improves the immunological response obtained with tenofovir + ddI or whether it is better to perform a double replacement of tenofovir and ddI with abacavir + lamivudine (joint formulation) in a single daily dose to achieve these objectives.

Eligibility criteria: Inclusion Criteria:

* Age \> 18 years.
* HIV-1 infected patients.
* Patients on triple HAART therapy including ddI + tenofovir plus a PI or NNRTI for at least 3 months.
* Patients with an undetectable HIV-1 viral load (\< 50 copies RNA / mL or \< centre's limit of detection) over the last 6 months.
* Not be on treatment with immunosuppressives, such as: hydroxyurea, interferon, ribavirin or cytostatics.
* Not be on treatment with interleukin-2 or other immunomodulators.
* Women may not be of fertile age (defined as at least one year from menopause or undergoing any surgical sterilisation technique), or must undertake to use a barrier contraceptive method during the study.
* Signature of the informed consent.

Exclusion Criteria:

* Incapacity to give informed consent.
* Bad adherence or treatment interruptions over the previous 6 months.
* Prior exposure to abacavir.
* HAART Therapy including ddI at a dose of 400mg + tenofovir if weight \> 60 kg or ddI 250 mg + tenofovir if weight \< 60 kg.
* Suspicion of cross resistances to abacavir and lamivudine.
* Hepatic or pancreatic analytical alterations 4 times above the limit of normality.
* Presence of opportunistic infections and/or recent tumours (\< 6 months).
* Patients participating in another clinical trial.

Primary outcomes:
measure: Proportion of patients that increase their number of CD4 lymphocytes with regard to the baseline.
timeFrame: At 12, 24, 36 and 48 weeks
Secondary outcomes:
measure: To evaluate the proportion of patients with viral load of HIV-1 <50 copies of the combinations studied during the follow-up period.
timeFrame: At 12, 24, 36 and 48 weeks.
measure: Incidence of new clinical adverse events that appear .
timeFrame: during 48 weeks of follow-up
measure: Evolution of the clinical adverse events that were already present at the time they were included in the study.
timeFrame: during the 48 weeks of follow-up
measure: Rate of treatment drop-outs due to the appearance of adverse events
timeFrame: during the 48 weeks of follow-up
measure: Incidence of new laboratory alterations that appear during the follow-up period (change in renal parameters, changes in lactate levels, modification of pancreatic enzymes, changes in lipid parameters).
timeFrame: during the follow-up period
measure: Evolution of the laboratory alterations that were already present at the time they were included in the study.
timeFrame: during the 48 weeks of follow-up
Other outcomes:
Locations:
city: Badalona
country: Spain
facility: Germans Trias i Pujol Hospital
state: Barcelona
city: Calella
country: Spain
facility: Hospital Sant Jaume de Calella
state: Barcelona
city: Mataro
country: Spain
facility: Hospital de Mataró
state: Barcelona
city: Bilbao
country: Spain
facility: Hospital Basurto
state: Bilabao
city: Jerez de la Frontera
country: Spain
facility: H. del S.A.S. Jerez de la Frontera
state: Cádiz
city: Barcelona
country: Spain
facility: Fundació Hospital de Granollers,
state: Granollers
city: El Ferrol
country: Spain
facility: Hospital Arquitecto Marcide
state: La Coruña
city: Torrelavega
country: Spain
facility: Hospital Sierrallana
state: Santander
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau
city: Barcelona
country: Spain
facility: Hospital Clínic de Barcelona
city: Castello
country: Spain
facility: Hospital General de Castellón, , Castellón,
city: Gandia
country: Spain
facility: H. San Fco Borja Gandia
city: Gijon
country: Spain
facility: Hospital de Cabueñes
city: Granada
country: Spain
facility: Hospital Clínico San Cecílio
city: Madrid
country: Spain
facility: Fundación Jiménez Diaz
city: Madrid
country: Spain
facility: Hospital Clínico San Carlos
city: Santander
country: Spain
facility: Hospital Marqués de Valdecilla
city: Sevilla
country: Spain
facility: Hospital Virgen Macarena
city: Tarragona
country: Spain
facility: Hospital Joan XXIII
city: Valencia
country: Spain
facility: Hospital Arnau de Vilanova
city: Vigo
country: Spain
facility: Hospital Xeral de Vigo
Study officials:
affiliation: Fundació Hospital de Granollers
name: Enric Pedrol, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: