Zoledronic Acid for Osteoporotic Fracture Prevention (ZEST II)

Study Details

Study Description

Brief Summary

The goal of this study is to perform the first fracture reduction clinical trial with a potent antiresorptive agent (intravenous zoledronic acid) in the most vulnerable long-term care population.

Condition or Disease	Intervention/Treatment	Phase
Osteoporotic Fractures Osteoporosis, Postmenopausal	Drug: Zoledronic acid Dietary Supplement: vitamin D Dietary Supplement: calcium Other: Saline	Phase 4

Detailed Description

Although close to 85% of frail women in long-term care (LTC) facilities have osteoporosis and the risk of osteoporotic fractures is nearly 10 times that of community dwelling elderly, few are treated and studies are scarce. It is postulated that in frail, LTC women an annual infusion of zoledronic acid, an antiresorptive therapy for osteoporosis, will:

be effective demonstrated by fracture reduction;
be safe.

To address these hypotheses, up to 1000 female LTC residents age 65 and older will be screened in order to enroll 310 eligible for randomization in a 3 year, randomized, double-blind, calcium and vitamin D controlled trial with the antiresorptive agent zoledronic acid. Use of an intravenous, once yearly agent avoids concerns of oral bisphosphonate side effects, poor absorption and burden on staff. Participants will reside in the long-term care settings associated with the Division of Geriatric Medicine, University of Pittsburgh and will include women with multiple comorbid conditions, functional and cognitive impairment, and limited mobility.

Study Design

Study Type:

Interventional

Actual Enrollment :

310 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Care Provider, Investigator)

Primary Purpose:

Treatment

Official Title:

ZEST II for Osteoporotic Fracture Prevention

Study Start Date :

Jan 1, 2016

Anticipated Primary Completion Date :

Sep 1, 2022

Anticipated Study Completion Date :

Mar 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Active Medication Group Annual dose: intravenous zoledronic acid (Reclast) 5.0 mg; vitamin D (800 IU/daily) and calcium (approximately 1200 mg/daily, dietary + supplements)	Drug: Zoledronic acid Annual intravenous 5.0 mg Other Names: Reclast Dietary Supplement: vitamin D 800 IU daily Dietary Supplement: calcium approximately 1200 mg (dietary and supplement)
Placebo Comparator: Placebo Group Annual dose: intravenous saline; vitamin D (800 IU/daily and calcium (approximately 1200 mg/daily, dietary + supplements)	Dietary Supplement: vitamin D 800 IU daily Dietary Supplement: calcium approximately 1200 mg (dietary and supplement) Other: Saline Annual intravenous saline placebo

Arm

Intervention/Treatment

Experimental: Active Medication Group

Annual dose: intravenous zoledronic acid (Reclast) 5.0 mg; vitamin D (800 IU/daily) and calcium (approximately 1200 mg/daily, dietary + supplements)

Drug: Zoledronic acid

Annual intravenous 5.0 mg

Other Names:

Reclast

Dietary Supplement: vitamin D

800 IU daily

Dietary Supplement: calcium

approximately 1200 mg (dietary and supplement)

Placebo Comparator: Placebo Group

Annual dose: intravenous saline; vitamin D (800 IU/daily and calcium (approximately 1200 mg/daily, dietary + supplements)

Dietary Supplement: vitamin D

800 IU daily

Dietary Supplement: calcium

approximately 1200 mg (dietary and supplement)

Other: Saline

Annual intravenous saline placebo

Outcome Measures

Primary Outcome Measures

Total non-traumatic incident fractures (vertebral and nonvertebral) except those viewed as severe trauma, cancer-related or fractures of the toes, finger or facial bones as identified by x-ray, CT, MRI, VFA imaging. [3 years]
Primary outcome will be assessed in all randomized women, optimally obtaining partial data in terms of person months of exposure and corresponding counts of fractures for analysis from those expiring/dropping out/moving before 3 years.

Eligibility Criteria

Criteria

Ages Eligible for Study:

65 Years and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Inclusion Criteria:

women age ≥65 years including those using assistive devices to maximize generalizability if they:

Reside in long-term care (LTC);
Have:

osteoporosis by axial bone density (spine, hip or forearm bone mineral density (BMD) T-score ≤ -2.5 SD); or
a previous adult fragility fracture of the spine or hip; or,
would be treated based on FRAX National Osteoporosis Foundation (NOF) treatment thresholds of a 10 year risk of ≥ 20% for a major osteoporotic fracture or ≥ 3% for hip fracture using femoral neck BMD.

Exclusion Criteria:

Men because osteoporosis is less common in men and our initial ZEST 1 study only included women.
Institutionalized women with subacute illnesses surviving or discharged in < 3 years.
Women currently on bisphosphonate, denosumab, or teriparatide therapy or who have been on a bisphosphonate for greater than 1 year during the previous 2 years because bisphosphonates are long acting.
Patients with a calculated creatinine clearance < 35 ml/min or who have a contraindication for bisphosphonates (allergy, hypocalcemia).