Raltegravir One Thousand Two Hundred vs Darunavir-cb in Immnunosupressed Patients: ROTDIP Study (ROTDIP)

Multicenter, Open, Pilot Clinical Trial Aimed to Compare the Efficacy of RAL1200 QD vs DRV-cb 800-150 QD Both in Combination With TAF/FTC in Patients With HIV Infection and CD4 Count Under 200 Cells/microL

Multicenter, randomized, open label pilot clinical trial with two parallel arms aimed to compare the efficacy of Raltegravir (RAL) 1200mg QD vs Darunavir/Cobicistat (DRV-cb) 800-150mg QD both in combination with alafenamide/emtricitabine (TAF/FTC) in patients with Human Inmunodefficiency Virus (HIV) infection and CD4<200 cells/microL

Study Overview

• Status: Unknown
• Conditions: HIV Infections
• Intervention / Treatment: Drug: Experimental: RAL QD; Drug: Active comparator: DRV/cb

Detailed Description

The trial consists of two parallel arms to study the therapeutic success of 48 weeks, tolerability, immunological recovery, persistence of treatment, safety and results reported by the subject in severely immunocompromised HIV infected patients (with an initial CD4 count <200 cells/μl) naive to antiretroviral therapy.

Included subjects will be randomized two to one (2:1) to RAL 1200mg QD plus FTC/TAF or DRV/cb (800-150mg) plus FTC/TAF.

• Study Type: Interventional
• Enrollment (Anticipated): 75
• Phase: Phase 4

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subjects ≥ 18 years of age.
• HIV-1 infection.
• Naive to antiretroviral treatment.
• CD4 count at the beginning of the study <200 cells/μl.
• Estimated glomerular filtration ≥ 50 mL / min, according to the formula CKD-EPI.
• Grant Informed Consent in writing to participate in the study

Exclusion Criteria:

• Breastfeeding, pregnant or women in childbearing age who do not commit to maintain barrier contraceptive measures during the trial.
• Concomitant use of any drug with possible pharmacological interaction with the study drugs that it is advisable to "avoid" through the database for interactions at the University of Liverpool (www.hiv-druginteractions.org).
• Previous use of any antiretroviral for HIV infection.
• Resistance to the study drugs, or presence of any contraindication to use it. The inclusion in the study can be carried out before receiving the result of the resistance test. Once it is received, in case of presenting any mutation of resistance to drugs of the indicated regimen, the patient will be removed from the study and will be offered the best available treatment for their medical condition at that time.
• Therapies that include interferon, interleukin-2, cytotoxic chemotherapy or immunosuppressants at the entrance to the study.
• Current consumption of alcohol or other substances that at the discretion of the investigator may interfere with subject's treatment compliance.
• Subjects who currently participate in any other clinical trial using a research product, with the exception of studies in which the treatment studied has been stopped for more than 12 weeks.
• AIDS event in diagnosis of HIV infection or in the 3 months prior to the inclusion of the study.
• Suspected severe hepatopathy (grades B or C of the Child-Pugh classification), of any origin, according to the clinician.
• Any other clinical condition or previous treatment that, in the investigator's judgment, makes the subject unsuitable for the study or unable to comply with the dosage requirements.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: RAL 1200 QD; Start treatment with Raltegravir (RAL) 1200mg QD plus tenofovir alafenamide/emtricitabine (FTC/TAF)	Drug: Experimental: RAL QD; Prescription of 2x RAL 600mg (1200MG) once daily; Other Names: Raltegravir (RAL) 600mg Oral Tablet
ACTIVE_COMPARATOR: DRV/cb; Start treatment with Darunavir/Cobicistat (DRV/cb) 800-150mg QD plus tenofovir alafenamide/emtricitabine (FTC/TAF)	Drug: Active comparator: DRV/cb; Prescription of DARUNAVIR/COBICISTAT 800 Mg-150 Mg once daily; Other Names: DARUNAVIR/COBICISTAT 800 Mg-150 Mg Oral Tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Compare efficacy of RAL 1200 mg QD versus DRV/cb 800-150 mg QD, both in combination with TAF/FTC	Number of patients that will improve when having raltegravir vs darunavir	48 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Virological failure	Number of patients in virological failure at week 48.	48 weeks
Compare the proportion of patients who interrupt the treatment for any reason	Number of patients that interrupt the treatment for any reason after 48 weeks.	48 weeks
Analyze change (percentage) in the number of CD4 lymphocytes	Percentage of change in the number of CD4 lymphocytes after 48 weeks.	48 weeks
Compare the proportion of patients with CD4>200 cells/μL at end of intervention	Compare the proportion of patients with CD4>200 cells/μL at end of intervention.	48 weeks
Percentage change in total cholesterol (TC)	Percentage of patients with change in total cholesterol (TC),	48 weeks
Percentage change in LDL and HDL cholesterol	Percentage of patients with change in LDL and HDL cholesterol	48 weeks
Percentage change in triglycerides	Percentage of patients with change the percentage change in triglycerides after 48 weeks	48 weeks
Percentage change in TC/HDL ratio	Percentage of patients with change in TC/HDL ratio	48 weeks
Change in Cardiovascular Risk 10-year predictive value (REGICOR).	Percentage of patients with change in Cardiovascular Risk 10-year predictive value (REGICOR).	48 weeks
Check GF modification using Chronic Kidney Disease Epidemiology (CKD-EPI) equation	Number of patiens with changes in glomerular filtration using Chronic Kidney Disease Epidemiology (CKD-EPI) equation.	48 weeks

Collaborators and Investigators

• Sponsor: Fundación Pública Andaluza para la Investigación de Málaga en Biomedicina y Salud
• Collaborators: Merck Sharp & Dohme LLC

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): April 1, 2019
• Primary Completion (ANTICIPATED): March 1, 2021
• Study Completion (ANTICIPATED): March 1, 2021

Study Registration Dates

• First Submitted: December 19, 2018
• First Submitted That Met QC Criteria: February 14, 2019
• First Posted (ACTUAL): February 15, 2019

Study Record Updates

• Last Update Posted (ACTUAL): February 15, 2019
• Last Update Submitted That Met QC Criteria: February 14, 2019
• Last Verified: February 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; Slow Virus Diseases; HIV Infections; Infections; Acquired Immunodeficiency Syndrome; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Protease Inhibitors; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; HIV Integrase Inhibitors; Integrase Inhibitors; HIV Protease Inhibitors; Viral Protease Inhibitors; Cobicistat; Raltegravir Potassium; Darunavir
• Other Study ID Numbers: FIMHCSVIH-2017

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No