Multicentre Study To Assess Changes In Bone Mineral Density Of The Switch From Protease Inhibitors To Dolutegravir In HIV-1-Infected Subjects With Low Bone Mineral Density

NCT01966822 | Completed Phase 3

• 1 other identifier: OSTEODOLU
• Study Type: interventional
• Target: 75
• Locations: 1 country
• Sites: 3

Brief Summary

Protease inhibitors (PI) have been associated with an acceleration of bone mineral density loss in HIV-infected individuals because of an enhanced osteoclast activity, although some controversial data have been also published. A first study suggest an increase of bone mineral density after switching from PI to raltegravir, the first generation integrase inhibitor, but there are no more data about this subject. Based on data that PI decrease bone mineral density by accelerating osteoclast cells and that the discontinuation of this drugs could improve bone mineralization, we propose a randomized prospective multicenter study to assess the impact of switching from PI to dolutegravir on bone mineral density in patients with low bone mineral density receiving a PI-containing regimen. At the same time, the study will help to assess the antiviral efficacy and safety of a PI-sparing regimen including dolutegravir as a simplification strategy in virologically suppressed patients.

Conditions

HIV-1 Infection

Keywords

Osteoporosis; Bone mineral density; Dual-energy X-ray absorptiometry; HIV infection; Dolutegravir; Integrase inhibitor

Outcome Measures

Primary Outcomes (3)

• Compare changes in Bone Mineral Density (BMO) measured by Dual-energy X-ray absorptiometry

  From Baseline to week 48

• Compare changes in femur T-score measured by DEXA

  From Baseline to week 48

• Compare changes in lumbar spine (L1-L4) T-score measured by DEXA

  From Baseline to week 48

Secondary Outcomes (24)

• HIV-1 viral load

  Baseline

• HIV-1 viral load

  week 4

• HIV-1 viral load

  week 12

• HIV-1 viral load

  week 24

• HIV-1 viral load

  week 48

Study Arms (2)

Dolutegravir 50mg

EXPERIMENTAL

Dolutegravir 50mg every 24 hours + Kivexa (ABC+3TC)

Drug: Dolutegravir, 50mg every 24 hours

Protease Inhibitor/ritonavir

ACTIVE COMPARATOR

Protease Inhibitor/ritonavir + Kivexa (ABC+3TC)

Drug: Protease Inhibitor/ritonavir

Interventions

Dolutegravir, 50mg every 24 hours DRUG

Dolutegravir, 50mg every 24 hours

Dolutegravir 50mg

Protease Inhibitor/ritonavir DRUG

Protease Inhibitor/ritonavir

Protease Inhibitor/ritonavir

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• HIV-infected patients over 18 years.
• In current antiretroviral therapy with abacavir and lamivudine (Kivexa) plus ritonavir-boosted PI, at least 6 months.
• Viral suppression (HIV RNA \<50 copies / ml) for at least 12 months.
• T-score ≤ -1 evaluated by DEXA (done in the last 6 months).
• Signed informed consent.
• In potential childbearing women, commitment to use barrier contraceptive method throughout the study.

You may not qualify if:

• Suspected or documented resistance to integrase inhibitors or reverse transcriptase inhibitors, nucleoside analogues.
• Osteoporosis / osteopenia secondary (testosterone deficiency, thyroid disease ...), except vitamin D deficiency
• Treatment with bisphosphonates in the last 6 months.
• Have used integrase inhibitors
• Pregnant or breastfeeding.
• Patients with alanine aminotransferase (ALT)\> 5 times the upper limit of normal (ULN) or ALT ≥ 3 times ULN and bilirubin ≥ 1.5 times ULN (direct bilirubin\> 35%)
• Patients with severe hepatic dysfunction (Class B or C) according to the Child-Pugh classification
• Patients infected with hepatitis B virus (HBV) who can not use entecavir or telbivudine.
• Patients infected with hepatitis C virus (HCV) in which is expected to begin treatment during the study.

Sponsors & Collaborators

• Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia: lead

Study Sites (3)

GermansTrias i Pujol Hospital

Badalona, Barcelona, 08916, Spain

Location

Hospital de la Santa Creu i Sant Pau

Barcelona, Barcelona, 08025, Spain

Location

Hospital Clínico San Carlos

Madrid, Madrid, 28040, Spain

Location

MeSH Terms

Conditions

Osteoporosis; HIV Infections

Interventions

dolutegravir; Protease Inhibitors; Ritonavir

Condition Hierarchy (Ancestors)

Bone Diseases, Metabolic; Bone Diseases; Musculoskeletal Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 7, 2013
• First Posted: October 22, 2013
• Study Start: January 1, 2014
• Primary Completion: October 1, 2015
• Study Completion: October 1, 2015
• Last Updated: November 30, 2015

Record last verified: 2015-11

Locations

ES (3)