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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

NCT ID: NCT01966822

Last Updated: 2015-11-30

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

75 participants

Study Classification

INTERVENTIONAL

Study Start Date

2014-01-31

Study Completion Date

2015-10-31

Brief Summary

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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.

Detailed Description

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The second generation integrase inhibitor dolutegravir has demonstrated good virological and immunological outcomes in antiretroviral-naive subjects, compared with efavirenz, (SPRING 1 study). As well, it is active against HIV strains resistant to first-generation inhibitors raltegravir and elvitegravir in heavily treatment-experienced patients (VIKING study).

Additionally, it was safe and well tolerated after two years of use. It is administered once daily with no need for boosting, no food requirements and has a long half-life. The easy posology and its pharmacokinetics, together with the antiviral potency, make this drug a good alternative as a simplification approach. However, no clinical data are available supporting the switch of protease inhibitors or no nucleoside reverse transcriptase inhibitors to dolutegravir in virologically suppressed HIV-treated subjects.

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

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HIV-1 Infection

Keywords

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

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Dolutegravir 50mg

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

Group Type EXPERIMENTAL

Dolutegravir, 50mg every 24 hours

Intervention Type DRUG

Dolutegravir, 50mg every 24 hours

Protease Inhibitor/ritonavir

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

Group Type ACTIVE_COMPARATOR

Protease Inhibitor/ritonavir

Intervention Type DRUG

Protease Inhibitor/ritonavir

Interventions

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Dolutegravir, 50mg every 24 hours

Dolutegravir, 50mg every 24 hours

Intervention Type DRUG

Protease Inhibitor/ritonavir

Protease Inhibitor/ritonavir

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

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

Exclusion Criteria

1. Suspected or documented resistance to integrase inhibitors or reverse transcriptase inhibitors, nucleoside analogues.
2. Osteoporosis / osteopenia secondary (testosterone deficiency, thyroid disease ...), except vitamin D deficiency
3. Treatment with bisphosphonates in the last 6 months.
4. Have used integrase inhibitors
5. Pregnant or breastfeeding.
6. 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%)
7. Patients with severe hepatic dysfunction (Class B or C) according to the Child-Pugh classification
8. Patients infected with hepatitis B virus (HBV) who can not use entecavir or telbivudine.
9. Patients infected with hepatitis C virus (HCV) in which is expected to begin treatment during the study.
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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GermansTrias i Pujol Hospital

Badalona, Barcelona, Spain

Site Status

Hospital de la Santa Creu i Sant Pau

Barcelona, Barcelona, Spain

Site Status

Hospital Clínico San Carlos

Madrid, Madrid, Spain

Site Status

Countries

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Spain

Other Identifiers

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OSTEODOLU

Identifier Type: -

Identifier Source: org_study_id