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

This study has been completed.
Sponsor:
Information provided by:
Hospital de Granollers
ClinicalTrials.gov Identifier:
NCT00338390
First received: June 15, 2006
Last updated: October 30, 2008
Last verified: October 2008
  Purpose

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.


Condition Intervention Phase
HIV Infections
Drug: Abacavir
Drug: Didanosine
Drug: Abacavir+Lamivudine
Phase 3

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

Resource links provided by NLM:


Further study details as provided by Hospital de Granollers:

Primary Outcome Measures:
  • Proportion of patients that increase their number of CD4 lymphocytes with regard to the baseline. [ Time Frame: At 12, 24, 36 and 48 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To evaluate the proportion of patients with viral load of HIV-1 <50 copies of the combinations studied during the follow-up period. [ Time Frame: At 12, 24, 36 and 48 weeks. ] [ Designated as safety issue: Yes ]
  • Incidence of new clinical adverse events that appear . [ Time Frame: during 48 weeks of follow-up ] [ Designated as safety issue: Yes ]
  • Evolution of the clinical adverse events that were already present at the time they were included in the study. [ Time Frame: during the 48 weeks of follow-up ] [ Designated as safety issue: Yes ]
  • Rate of treatment drop-outs due to the appearance of adverse events [ Time Frame: during the 48 weeks of follow-up ] [ Designated as safety issue: Yes ]
  • 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). [ Time Frame: during the follow-up period ] [ Designated as safety issue: Yes ]
  • Evolution of the laboratory alterations that were already present at the time they were included in the study. [ Time Frame: during the 48 weeks of follow-up ] [ Designated as safety issue: Yes ]

Enrollment: 75
Study Start Date: April 2005
Study Completion Date: February 2007
Primary Completion Date: February 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
No Intervention: 1
Maintain antiretroviral treatment
Experimental: 2
Change tenofovir to abacavir and increase didanosine dose to 400 mg/day if weight is > 60 Kg. or to 250mg/day if weight is < 60 kg.
Drug: Abacavir
Change tenofovir to abacavir
Other Name: n/h.
Drug: Didanosine
Increase didanosine dose to 400 mg/day if weight is > 60 Kg. or to 250mg/day if weight is < 60 kg.
Other Name: n/h.
Experimental: 3
Change tenofovir and didanosine to abacavir + lamivudine (600mg+300 mg/day in one single tablet).
Drug: Abacavir+Lamivudine
Change tenofovir and didanosine to abacavir + lamivudine (600mg+300 mg/day in one single tablet).
Other Name: n/h.

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

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00338390

Locations
Spain
Germans Trias i Pujol Hospital
Badalona, Barcelona, Spain, 08916
Hospital Sant Jaume de Calella
Calella, Barcelona, Spain, 08370
Hospital de Mataró
Mataro, Barcelona, Spain, 08304
Hospital Basurto
Bilbao, Bilabao, Spain, 48013
H. del S.A.S. Jerez de la Frontera
Jerez de la Frontera, Cádiz, Spain, 11407
Fundació Hospital de Granollers,
Barcelona, Granollers, Spain, 08400
Hospital Arquitecto Marcide
El Ferrol, La Coruña, Spain, 15405
Hospital Sierrallana
Torrelavega, Santander, Spain, 39300
Hospital Clínic de Barcelona
Barcelona, Spain, 08036
Hospital de la Santa Creu i Sant Pau
Barcelona, Spain, 08025
Hospital General de Castellón, , Castellón,
Castello, Spain, 12004
H. San Fco Borja Gandia
Gandia, Spain, 46700
Hospital de Cabueñes
Gijon, Spain, 33394
Hospital Clínico San Cecílio
Granada, Spain, 18012
Hospital Clínico San Carlos
Madrid, Spain, 28040
Fundación Jiménez Diaz
Madrid, Spain, 28040
Hospital Marqués de Valdecilla
Santander, Spain, 39008
Hospital Virgen Macarena
Sevilla, Spain, 41009
Hospital Joan XXIII
Tarragona, Spain, 43007
Hospital Arnau de Vilanova
Valencia, Spain, 46015
Hospital Xeral de Vigo
Vigo, Spain, 36204
Sponsors and Collaborators
Hospital de Granollers
Investigators
Principal Investigator: Enric Pedrol, MD, PhD Fundació Hospital de Granollers
  More Information

No publications provided

ClinicalTrials.gov Identifier: NCT00338390     History of Changes
Other Study ID Numbers: EUROPA, 2004-003749-42
Study First Received: June 15, 2006
Last Updated: October 30, 2008
Health Authority: Spain: Ministry of Health

Keywords provided by Hospital de Granollers:
Antiretrovirals
CD4 cell count
toxicity

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Didanosine
Lamivudine
Tenofovir
Tenofovir disoproxil
Abacavir
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Anti-HIV Agents

ClinicalTrials.gov processed this record on September 11, 2014