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

HIV-1 Infection Clinical Trial

Official title:

Effects of Losartan and Antiretroviral Regimen Containing Raltegravir in Fibrosis Inflammation

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01529749
• Other study ID #: HIV-IMMUNESARTAN
• Secondary ID: 2011-002071-42
• Status: Completed
• Phase: Phase 4
• Start date: February 2012
• Est. completion date: February 2016

Study information

• Verified date: June 2019
• Source: Hospital Clinic of Barcelona
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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%.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 48
• Est. completion date: February 2016
• Est. primary completion date: March 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• HIV-1 Infection
• Inflammation
• Neurocognitive Disorders

Intervention

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.
• EFV/FTC/TDF
600/200/245 mg, od, oral
• FTC/TDF + MK-0518
FTC/TDF --> 200/245 mg, oral MK-0518 --> 400 mg, oral
• 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.

Locations

Country	Name	City	State
Spain	Hospital Clinic	Barcelona

Sponsors (1)

Lead Sponsor	Collaborator
Felipe Garcia

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of Patients With 50% Reduction of Fibrosis in Lymphatic Tissue.		48 weeks
Secondary	Proportion of Patients With Changes in the Levels of IL-6 in Different Groups.		48 weeks
Secondary	Proportion of Patients With Changes in the Levels of CRP in Different Groups.		48 weeks
Secondary	Proportion of Patients With Changes in the Levels of D-dimer in Different Groups.		48 weeks
Secondary	Proportion of Patients With Increased CD4 in Peripheral Blood.		48 weeks
Secondary	Proportion of Patients With Increased CD4 in Lymphatic Tissue.		week 48
Secondary	Proportion of Patients With Undetectable Plasma Viral Load in Different Groups		48 weeks
Secondary	Proportion of Patients With Undetectable Viral Load in Lymphatic Tissue in Different Groups		week 48
Secondary	Changes in the CD4/CD8 Ratio in Peripheral Blood in Different Groups.		48 weeks
Secondary	Proportion of Patients With Reduced Intima-media Complex in Carotid Ultrasound in Different Groups.		48 weeks
Secondary	Proportion of Patients With Changes in Levels of Metalloproteinases		48 weeks
Secondary	Proportion of Patients With Changes in Levels of beta2-microglobulin.		48 weeks
Secondary	Proportion of Patients With Changes in Levels of CSF Cells.		48 weeks
Secondary	Proportion of Patients With Changes in Levels of Proteins.		48 weeks
Secondary	Proportion of Patients With Improvement in Neuropsychological Test		48 weeks
Secondary	Number of Participants With Adverse Events and Laboratory Abnormalities in the Different Groups.		up to 48 weeks
Secondary	Changes in CD4 CD38+ HLADR+ (%)	Marker of activation in CD4 T cells. This Outcome Measure is reporting a change in the percentage of CD4 CD38+ HLADR+ T cells at 48 months minus the percentage at 0 weeks (baseline)	0, 48 weeks