Study to Evaluate Changes in CD4 on Replacing TDF With ABC or DDI+TDF With ABC+3TC

HIV Infections Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00338390
• Other study ID #: EUROPA
• Secondary ID: 2004-003749-42
• Status: Completed
• Phase: Phase 3
• First received: June 15, 2006
• Last updated: March 19, 2015
• Start date: April 2005
• Est. completion date: February 2007

Study information

• Verified date: October 2008
• Source: Hospital de Granollers
• Contact: n/a
• Is FDA regulated: No
• Health authority: Spain: Ministry of Health
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 75
• Est. completion date: February 2007
• Est. primary completion date: February 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

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.

Study Design

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

Related Conditions & MeSH terms

• HIV Infections

Intervention

Drug:
• Abacavir
Change tenofovir to abacavir
• Didanosine
Increase didanosine dose to 400 mg/day if weight is > 60 Kg. or to 250mg/day if weight is < 60 kg.
• Abacavir+Lamivudine
Change tenofovir and didanosine to abacavir + lamivudine (600mg+300 mg/day in one single tablet).

Locations

Country	Name	City	State
Spain	Germans Trias i Pujol Hospital	Badalona	Barcelona
Spain	Fundació Hospital de Granollers,	Barcelona	Granollers
Spain	Hospital Clínic de Barcelona	Barcelona
Spain	Hospital de la Santa Creu i Sant Pau	Barcelona
Spain	Hospital Basurto	Bilbao	Bilabao
Spain	Hospital Sant Jaume de Calella	Calella	Barcelona
Spain	Hospital General de Castellón, , Castellón,	Castello
Spain	Hospital Arquitecto Marcide	El Ferrol	La Coruña
Spain	H. San Fco Borja Gandia	Gandia
Spain	Hospital de Cabueñes	Gijon
Spain	Hospital Clínico San Cecílio	Granada
Spain	H. del S.A.S. Jerez de la Frontera	Jerez de la Frontera	Cádiz
Spain	Fundación Jiménez Diaz	Madrid
Spain	Hospital Clínico San Carlos	Madrid
Spain	Hospital de Mataró	Mataro	Barcelona
Spain	Hospital Marqués de Valdecilla	Santander
Spain	Hospital Virgen Macarena	Sevilla
Spain	Hospital Joan XXIII	Tarragona
Spain	Hospital Sierrallana	Torrelavega	Santander
Spain	Hospital Arnau de Vilanova	Valencia
Spain	Hospital Xeral de Vigo	Vigo

Sponsors (1)

Lead Sponsor	Collaborator
Hospital de Granollers

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of patients that increase their number of CD4 lymphocytes with regard to the baseline.		At 12, 24, 36 and 48 weeks	No
Secondary	To evaluate the proportion of patients with viral load of HIV-1 <50 copies of the combinations studied during the follow-up period.		At 12, 24, 36 and 48 weeks.	Yes
Secondary	Incidence of new clinical adverse events that appear .		during 48 weeks of follow-up	Yes
Secondary	Evolution of the clinical adverse events that were already present at the time they were included in the study.		during the 48 weeks of follow-up	Yes
Secondary	Rate of treatment drop-outs due to the appearance of adverse events		during the 48 weeks of follow-up	Yes
Secondary	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).		during the follow-up period	Yes
Secondary	Evolution of the laboratory alterations that were already present at the time they were included in the study.		during the 48 weeks of follow-up	Yes