Bone Antiresorptive Therapy With Antiretroviral Initiation (BATARI) Pilot Trial

Study Overview
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Brief Summary
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This is a two-site, three-arm, open-label, pilot randomized controlled trial of bone anti-resorptive therapy during ART initiation in HIV-infected adults. Thirty (30) treatment-naïve HIV-infected adults initiating eligible first-line ART regimens will be randomized in a 1:1:1 fashion to one of the following three arms: no bone anti-resorptive therapy (standard of care) concomitant initiation of a 24 week course of co-formulated alendronate/vitamin D; a 24 week delay in initiation of a 24 week course of alendronate/vitamin D Assessments (including clinical evaluation, questionnaires, adherence, basic laboratory evaluation, and BMD measurement) will be performed at baseline, 24 and 48 weeks. The primary objective will involve calculation of σ and ρ using all data; δ will be estimated by comparing the two alendronate arms pooled to the no-treatment arm.

Official Title
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Bone Antiresorptive Therapy With Antiretroviral Initiation (BATARI) Pilot Trial

Conditions
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HIV

Intervention / Treatment
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* Drug: alendronate/vitamin D


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Documented HIV-1 infection Adult (aged >18 years or as per local guidelines) Premenopausal, if female Antiretroviral-naïve Starting first-line ART including tenofovir/emtricitabine with either efavirenz (co-formulated as Atripla®) or elvitegravir, cobicistat (co-formulated as Stribild®) Low (<10%) ten-year fracture risk as assessed by the FRAX score validated for Canadian populations Exclusion Criteria: Presence of established osteoporosis at baseline as determined by BMD measurement Prior or current use of any bone anti-resorptive therapy (eg. bisphosphonate, estrogens with the exception of oral contraceptive pills, etc.) Inability to communicate in English Creatinine clearance <35 mL/min (using Cockcroft-Gault formula) Hypersensitivity to alendronate, other bisphosphonates, or any component of the formulation Hypocalcemia Abnormalities of the esophagus which delay esophageal emptying such as stricture or achalasia Inability to stand or sit upright for at least 30 minutes Pregnancy, active plans to become pregnant, or lactation

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: no bone anti-resorptive therapy<br>(standard of care) | |
| Experimental: 24-week tx of alendronate/vitamin D<br>Concomitant initiation of a 24 week course of co-formulated alendronate/vitamin D | Drug: alendronate/vitamin D<br>* once weekly 70mg oral dose of alendronate co-formulated with 5600IU vitamin D3 (cholecalciferol) for 24 weeks.<br>* Other names: Fosavance 70/56;|
| Experimental: Delayed 24-week tx of alendronate/vitamin D<br>a 24 week delay in initiation of a 24 week course of alendronate/vitamin D | Drug: alendronate/vitamin D<br>* once weekly 70mg oral dose of alendronate co-formulated with 5600IU vitamin D3 (cholecalciferol) for 24 weeks.<br>* Other names: Fosavance 70/56;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage changes in BMD at a) the lumbar spine and b) proximal femur | The primary analysis will compare the percentage changes in BMD for the two alendronate/vitamin D arms pooled against the control arm. | 48 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Feasibility | The proportion of patients who are eligible and who consent to participate will be calculated, and the timeliness (rate) of enrollment will be described, to further inform the feasibility of a larger randomized controlled trial. | 48 weeks | 
| Acceptability | Using standardized questions, participants will be asked about the acceptability of the alendronate therapy (including the experience of pill-taking and the weekly schedule) | 48 weeks | 
| Safety/Tolerability | As per Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events. | 48 weeks | 
| Adherence | Adherence with anti-resorptive therapy will be assessed by pill count and questionnaire. | 48 weeks | 
| Bone Biomarkers | Two bone biomarkers will be assessed: cross-linked carboxyterminal-telopeptide (CTX) and aminoterminal propeptide of type 1 collagen (P1NP). | 48 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV, osteoporosis, bone Mineral Density, alendronate, vitamin D