Effects of Losartan and Antiretroviral Regimen Containing Raltegravir in Fibrosis Inflammation Mediators, Cardiovascular Risk and Neurocognitive Disorders in HIV Infected Patients Previously Effectively Treated

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2014 by Hospital Clinic of Barcelona
Sponsor:
Information provided by (Responsible Party):
Felipe Garcia, Hospital Clinic of Barcelona
ClinicalTrials.gov Identifier:
NCT01529749
First received: February 8, 2012
Last updated: February 25, 2014
Last verified: February 2014
  Purpose

This is a open controlled trial in which 48 HIV-1 patients successfully treated with EFV/FTC/TDF will be randomized to one of 4 groups in equal proportion between arms (1:1). The four arms are as follows:

Arm I: EFV / FTC / TDF (n = 12) Arm II: EFV / FTC / TDF + LST (n = 12) Arm III: FTC / TDF + MK-0518 (n = 12) Arm IV: FTC / TDF + LST + MK-0518 (n = 12)

The allocation will take place in two phases:

Phase I: 24 patients 1:1 receiving EFV/FTC/TDF vs. EFV/FTC/TDF + Losartan

If losartan arm shows benefits we will proceed to the second phase:

Phase II: 24 patients 1:1 to receive FTC/TDF+ MK-0518 versus FTC/TDF + MK-0518 + losartan.

Patients will be followed up during 12 months to determinate the proportion of patients with decreased collagen deposition in TL equal to or greater than 50%.


Condition Intervention Phase
HIV-1
Drug: EFV/FTC/TDF + Losartan
Drug: EFV/FTC/TDF
Drug: FTC/TDF + MK-0518
Drug: FTC/TDF+MK-0518+Losartan
Phase 4

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

Resource links provided by NLM:


Further study details as provided by Hospital Clinic of Barcelona:

Primary Outcome Measures:
  • Proportion of patients with 50% reduction of fibrosis in lymphatic tissue. [ Time Frame: 48 weeks ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Proportion of patients with changes in the levels of IL-6, D-dimer and CRP in different groups. [ Time Frame: 12, 24, 36 and 48 weeks ] [ Designated as safety issue: Yes ]
  • Proportion of patients with increased CD4 in peripheral blood and in lymphatic tissue. [ Time Frame: peripheral blood: 12, 24, 36 and 48 weeks, Lymphatic tissue: week 48 ] [ Designated as safety issue: Yes ]
  • Proportion of patients with undetectable plasma viral load and decreased in lymphatic tissue in different groups [ Time Frame: VL in plasma: 12, 24, 36, 48 weeks, Lymphatic tissue: week 48 ] [ Designated as safety issue: Yes ]
  • Proportion of patients with changes in the CD4/CD8 ratio in peripheral blood in different groups. [ Time Frame: 12, 24, 25 and 48 weeks ] [ Designated as safety issue: Yes ]
  • Proportion of patients with reduced intima-media complex in carotid ultrasound in different groups. [ Time Frame: 48 weeks ] [ Designated as safety issue: Yes ]
  • Proportion of patients with changes in levels of metalloproteinases and their inhibitors, beta2-microglobulin and CSF cells and proteins. [ Time Frame: 48 weeks ] [ Designated as safety issue: Yes ]
  • Proportion of patients with improvement in neuropsychological test CDS [ Time Frame: 48 weeks ] [ Designated as safety issue: Yes ]
  • Incidence and types of adverse events and laboratory abnormalities in the different groups. [ Time Frame: 12, 24, 36 and 48 weeks ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 48
Study Start Date: February 2012
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: EFV/FTC/TDF Drug: EFV/FTC/TDF
600/200/245 mg, od, oral
Experimental: EFV/FTC/TDF + Losartan Drug: EFV/FTC/TDF + Losartan
EFV/FTC/TDF --> oral, 600/200/245 mg, od Losartan --> initial dose 50 mg/24h, in patients with good tolerance, dose will be increased to 100 mg/24H in week 12.
Experimental: FTC/TDF + MK-0518 Drug: FTC/TDF + MK-0518
FTC/TDF --> 200/245 mg, oral MK-0518 --> 400 mg, oral
Experimental: FTC/TDF+MK-0518+Losartan Drug: FTC/TDF+MK-0518+Losartan
FTC/TDF --> 200/245 mg, oral MK-0518 --> 400 mg, oral Losartan --> -> initial dose 50 mg/24h, in patients with good tolerance, dose will be increased to 100 mg/24n in week 12.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patients older than 18 years.
  2. Patients with HIV infection in antiretroviral treatment with EFV / FTC / TDF with undetectable viral load (VL <37 copies) for at least 48 weeks.
  3. Nadir CD4 +> 250 cells/mm3.
  4. Patients, properly informed, give their written consent to participate in the study.

Exclusion Criteria:

  1. Criteria for patients with AIDS.
  2. Patients with active opportunistic diseases.
  3. Patients coinfected with HCV.
  4. Patients without tonsillar tissue.
  5. Treatment with other drugs receptor antagonists or angiotensin II converting enzyme inhibitors, angiotensin II.
  6. Kidney failure.(Glomerular Filtration Rate (GFR < 60 mL/mn)
  7. Severe liver failure (PT> 60% ).
  8. Pregnant women
  9. Known hypersensitivity or contraindication to any study drug.
  10. determination of blood pressure (BP) <100/60 mmHg
  11. Hyponatremia with serum Na numbers <132 Meq / l
  12. History of chronic vomiting the last 6 months
  13. History of chronic diarrhea the last 6 months
  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: NCT01529749

Contacts
Contact: Felipe Garcia, MD fgarcia@clinic.ub.es

Locations
Spain
Hospital Clinic Recruiting
Barcelona, Spain, 08036
Contact: Felipe Garcia, MD       fgarcia@clinic.ub.es   
Sponsors and Collaborators
Hospital Clinic of Barcelona
  More Information

No publications provided

Responsible Party: Felipe Garcia, Dr, Hospital Clinic of Barcelona
ClinicalTrials.gov Identifier: NCT01529749     History of Changes
Other Study ID Numbers: HIV-IMMUNESARTAN
Study First Received: February 8, 2012
Last Updated: February 25, 2014
Health Authority: Spain: Spanish Agency of Medicines

Additional relevant MeSH terms:
Losartan
Anti-Arrhythmia Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Antihypertensive Agents
Angiotensin II Type 1 Receptor Blockers
Angiotensin Receptor Antagonists
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 14, 2014