Trial To Assess The Lipid-Lowering Effect Of Adding Tenofovir/Emtricitabine Co-Formulation Vs Placebo To Hiv-1-Infected Subjects With Dyslipidemia And Sustained Viral Load Suppression Under Monotherapy With Ritonavir-Boosted Protease Inhibitors

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Fundacio Lluita Contra la SIDA
ClinicalTrials.gov Identifier:
NCT01458977
First received: October 21, 2011
Last updated: June 18, 2014
Last verified: June 2014
  Purpose

This is a phase IV, multicenter, prospective, randomised, crossover, double blind, placebo-controlled and proof of concept clinical trial.

All subjects fulfilling inclusion criteria will be randomised to add either TDF/FTC co-formulation (group A) or placebo (Group B) to their current PI/r regimen, i.e.: DRV/r 800/100 mg QD or LPV/r 400/100 BID. This will be followed by a crossover addition of TDF/FTC co-formulation or placebo.

Randomization will be centralised in the CRO FLS-Research Support and will be stratified by DRV/r or LPV/r intake at baseline to ensure equal distribution in both arms. TDF/FTC co-formulation or Placebo will be provided in a double-blinded fashion, i.e.: neither the treating physician nor the patient will know whether the patient is receiving TDF/FTC or placebo.

All subjects will receive dietary counselling to promote lipid-lowering diet provided by a specialised dietician throughout the study.

The expected duration of the study for each participant will be 36 weeks. There will be 6 visits: screening, baseline and weeks 4, 12, 24 and 36.


Condition Intervention Phase
HIV
Dyslipidemia
Drug: Truvada® (300 mg tenofovir disoproxil fumarato/200 mg emtricitabine)
Drug: Placebo
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Prospective, Randomised, Crossover, Double-Blind, Placebo-Controlled Trial To Assess The Lipid-Lowering Effect Of Adding Tenofovir/Emtricitabine Co-Formulation Vs Placebo To Hiv-1-Infected Subjects With Dyslipidemia And Sustained Viral Load Suppression Under Monotherapy With Ritonavir-Boosted Protease Inhibitors

Resource links provided by NLM:


Further study details as provided by Fundacio Lluita Contra la SIDA:

Primary Outcome Measures:
  • Total fasting cholesterol [ Time Frame: Baseline, week 4, 12, 24 and 36 ] [ Designated as safety issue: Yes ]
  • LDL-cholesterol [ Time Frame: Baseline, week 4, 12, 24 and 36 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • CD4 cell count [ Time Frame: Baseline, week 4, 12, 24 and 36 ] [ Designated as safety issue: No ]
  • Changes in liver enzymes [ Time Frame: Baseline, week 4, 12, 24 and 36 ] [ Designated as safety issue: Yes ]
  • Changes in phosphate [ Time Frame: Baseline, week 4, 12, 24 and 36 ] [ Designated as safety issue: Yes ]
  • Changes in creatinine [ Time Frame: Baseline, week 4, 12, 24 and 36 ] [ Designated as safety issue: Yes ]
  • Changes in glomerular filtration rate [ Time Frame: Baseline, week 4, 12, 24 and 36 ] [ Designated as safety issue: Yes ]
  • Changes in HDL cholesterol [ Time Frame: Baseline, week 4, 12, 24 and 36 ] [ Designated as safety issue: Yes ]
  • Changes in triglycerides [ Time Frame: Baseline, week 4, 12, 24 and 36 ] [ Designated as safety issue: Yes ]
  • Adverse events [ Time Frame: Baseline, week 4, 12, 24 and 36 ] [ Designated as safety issue: Yes ]
  • Resistance mutations [ Time Frame: Baseline, week 4, 12, 24 and 36 ] [ Designated as safety issue: No ]
  • lipid-lowering drugs [ Time Frame: Baseline, week 4, 12, 24 and 36 ] [ Designated as safety issue: Yes ]

Enrollment: 48
Study Start Date: January 2012
Study Completion Date: February 2014
Primary Completion Date: February 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: TDF/FTC (3 months) + Placebo (6 months)
TDF/FTC (3 months) + Placebo (6 months)
Drug: Truvada® (300 mg tenofovir disoproxil fumarato/200 mg emtricitabine)
TDF/FTC 300/200mg daily during 3 months + Placebo during 6 months
Other Name: N/H
Placebo Comparator: Placebo (3 months) + TDF/FTC (3 months) + Placebo (3 months)
Placebo (3 months) + TDF/FTC (3 months) + Placebo (3 months)
Drug: Placebo
Placebo during 3 months + TDF/FTC 300/200mg daily during 3 months + Placebo during 3 months
Other Name: N/H

Detailed Description:

This is a phase IV, multicenter,, prospective, randomised, crossover, double blind, placebo‐controlled and proof of concept clinical trial. The trial was conducted in a total sample of 60 patients (30 patients per group), which assures adequate power to detect differences. This study is adequate to demonstrate the lipid-lowering effect of TDF/FTC co-formulation addition in patients with dyslipidemia and stable monotherapy antiretroviral treatment.

All subjects fulfilling inclusion criteria will be randomised to add either TDF/FTC co-formulation (group A) or placebo (Group B) to their current PI/r regimen, i.e.: DRV/r 800/100 mg QD or LPV/r 400/100 BID. This will be followed by a crossover addition of TDF/FTC co-formulation or placebo.

In Group A the expected changes in cholesterol values, regarding baseline, can be observed 3 months after TDF/FTC addition. After this, a period of 3 months with placebo will act as a washout period, allowing establishing comparisons intra-patient. Finally, another period of 3 months with placebo will permit to establish comparisons with the first 3-month TDF/FTC intervention. In Group B, subjects will follow a 3-month placebo period, later a 3-month TDF/FTC intervention and finally a placebo period that will act as a wash-out.

Randomization will be centralised in the CRO FLS-Research Support and will be stratified by DRV/r or LPV/r intake at baseline to ensure equal distribution in both arms. TDF/FTC co-formulation or Placebo will be provided in a double-blinded fashion, i.e.: neither the treating physician nor the patient will know whether the patient is receiving TDF/FTC or placebo.

All subjects will receive dietary counselling to promote lipid-lowering diet provided by a specialised dietician throughout the study.

The expected duration of the study for each participant will be 36 weeks. There will be 6 visits: screening, baseline and weeks 4, 12, 24 and 36.

The date for the inclusion of the first patient was November 2011 and the end of the last patient follow-up has been in February 2014. The enrolment period has been 18 months. The final study report will be submitted before November 2014.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Age ≥ 18 years
  2. Chronic HIV-1 infection
  3. Antiretroviral treatment with either DRV/r (800/100 mg QD) or LPV/r (400/100 mg BID) monotherapy during at least 6 months prior to screening.
  4. Fasting total cholesterol or LDL-cholesterol levels ≥ 200 and ≥130 mg/dL respectively, in the previous two consecutive tests obtained at least 4 weeks apart before screening.
  5. Calculated creatinine clearance ≥ 60 mL/min, according to the Cockcroft-Gault formula.
  6. Undetectable plasma HIV-1 RNA levels (< 50 copies/mL) during at least 6 months prior to screening.
  7. Adequate treatment adherence.
  8. Absence of TDF or FTC resistances.
  9. Written informed consent to participate into the study.

Exclusion Criteria:

  1. Acute infections or uncontrolled chronic infection in the 2 months previous to the inclusion or physical examination that, in the investigator's opinion, would compromise the patient's safety or outcome of the study
  2. Lactating, pregnancy or fertile women willing to be pregnant.
  3. Concomitant use of any drug with potential drug-drug interaction with DRV/r, LPV/r or TDF/FTC co-formulation at study entry.
  4. Concomitant use of any lipid-lowering drugs at study entry.
  5. Prior documented intolerance or hypersensitivity to TDF, FTC, LPV/r or DRV/r.
  6. Therapies including interferon, interleukin-2, cytotoxic chemotherapy or immunosuppressors at study entry.
  7. Acute or chronic renal documented pathologies.
  8. Documented resistance to any of the study drugs (either genotypic or phenotypic)
  9. Life expectancy less or equal to 1 year.
  10. Current alcohol or substance use judged by the investigator to potentially interfere with subject study compliance.
  11. Subjects currently taking part in any other clinical trial using an investigational product, with the exception of studies where the treatment studied have stopped for more than 12 weeks.
  12. Any other clinical condition or prior therapy that, in the opinion of the investigator, would make the subject unsuitable for the study or unable to comply with the dosing requirements.
  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: NCT01458977

Locations
Spain
Germans Trias i Pujol Hospital
Badalona, Barcelona, Spain, 08916
Hospital de Bellvitge
Hospitalet de Llobregat, Barcelona, Spain
Hospital Valle Hebrón
Barcelona, Spain, 08035
Sponsors and Collaborators
Fundacio Lluita Contra la SIDA
  More Information

No publications provided

Responsible Party: Fundacio Lluita Contra la SIDA
ClinicalTrials.gov Identifier: NCT01458977     History of Changes
Other Study ID Numbers: TULIP
Study First Received: October 21, 2011
Last Updated: June 18, 2014
Health Authority: Spain: Ministry of Health

Keywords provided by Fundacio Lluita Contra la SIDA:
Lípid-lowering effect
Tenofovir
Dyslipidemia

Additional relevant MeSH terms:
Dyslipidemias
Lipid Metabolism Disorders
Metabolic Diseases
Protease Inhibitors
Ritonavir
HIV Protease Inhibitors
Tenofovir
Tenofovir disoproxil
Emtricitabine
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors

ClinicalTrials.gov processed this record on September 11, 2014