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

HIV-1 Infection Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01966822
• Other study ID #: OSTEODOLU
• Status: Completed
• Phase: Phase 3
• First received: October 7, 2013
• Last updated: November 27, 2015
• Start date: January 2014
• Est. completion date: October 2015

Study information

• Verified date: November 2015
• Source: Fundacio Lluita Contra la SIDA
• Contact: n/a
• Is FDA regulated: No
• Health authority: Spain: Ministry of Health
• Study type: Interventional

Clinical Trial 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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 75
• Est. completion date: October 2015
• Est. primary completion date: October 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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.

Study Design

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

Related Conditions & MeSH terms

• HIV-1 Infection

Intervention

Drug:
• Dolutegravir, 50mg every 24 hours
Dolutegravir, 50mg every 24 hours
• Protease Inhibitor/ritonavir
Protease Inhibitor/ritonavir

Locations

Country	Name	City	State
Spain	GermansTrias i Pujol Hospital	Badalona	Barcelona
Spain	Hospital de la Santa Creu i Sant Pau	Barcelona
Spain	Hospital Clínico San Carlos	Madrid

Sponsors (1)

Lead Sponsor	Collaborator
Fundacio Lluita Contra la SIDA

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Compare changes in Bone Mineral Density (BMO) measured by Dual-energy X-ray absorptiometry		From Baseline to week 48	Yes
Primary	Compare changes in femur T-score measured by DEXA		From Baseline to week 48	Yes
Primary	Compare changes in lumbar spine (L1-L4) T-score measured by DEXA		From Baseline to week 48	Yes
Secondary	HIV-1 viral load		Baseline	No
Secondary	HIV-1 viral load		week 4	No
Secondary	HIV-1 viral load		week 12	No
Secondary	HIV-1 viral load		week 24	No
Secondary	HIV-1 viral load		week 48	No
Secondary	CD4+/CD8+ T lymphocytes count.		Baseline	No
Secondary	CD4+/CD8+ T lymphocytes count.		week 4	No
Secondary	CD4+/CD8+ T lymphocytes count.		week 12	No
Secondary	CD4+/CD8+ T lymphocytes count.		week 24	No
Secondary	CD4+/CD8+ T lymphocytes count.		week 48	No
Secondary	Genotypic test if virological failure occurs.		From baseline to week 48	No
Secondary	Compare changes in total cholesterol		at week 48 relative to baseline values	Yes
Secondary	Compare changes in HDL cholesterol		at week 48 relative to baseline values	Yes
Secondary	Compare changes in LDL cholesterol		at week 48 relative to baseline values	Yes
Secondary	Compare changes in triglyceride levels.		at week 48 relative to baseline values	Yes
Secondary	Compare changes in filtrate glomerular rate by MDRD equation		at week 48 relative to baseline values	Yes
Secondary	Compare changes in creatinine		at week 48 relative to baseline values	Yes
Secondary	Compare changes in albumine/creatinine ratio		at week 48 relative to baseline values	Yes
Secondary	Compare changes in proteinuria/creatinine ratio		at week 48 relative to baseline values	Yes
Secondary	Adverse events related to antiretroviral treatment (Toxicity).		From Baseline to week 48	Yes
Secondary	Patient withdrawal		From Baseline to week 48	Yes
Secondary	Compare changes in osteocalcin		at week 48 relative to baseline values	Yes
Secondary	Compare changes in alkaline phosphatase		at week 48 relative to baseline values	Yes
Secondary	Compare changes in telopeptide		at week 48 relative to baseline values	Yes