Zoledronic Acid for Osteoporosis in the Elderly (ZEST)

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
University of Pittsburgh
ClinicalTrials.gov Identifier:
NCT00558012
First received: November 13, 2007
Last updated: February 12, 2014
Last verified: February 2014
  Purpose

This trial will examine the safety, efficacy and feasibility of a single dose of intravenous zoledronic acid in the maintenance of skeletal integrity for frail, institutionalized women, who are most at risk for the deleterious outcomes of osteoporosis. The investigators will test the hypothesis that in institutionalized elderly women a single dose of intravenous zoledronic acid therapy will: (1) be efficacious as demonstrated by stability or improvement in bone mass measurements and reductions in bone turnover; (2) be safe and feasible; and (3) provide estimates for vertebral and nonvertebral fracture reduction in this cohort for use in planning a future study.


Condition Intervention
Osteoporosis
Bone Loss
Fragility Fractures
Drug: Intravenous zoledronic acid

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: Maintenance of Skeletal Integrity in Frail Elders

Resource links provided by NLM:


Further study details as provided by University of Pittsburgh:

Primary Outcome Measures:
  • Bone mineral density (BMD) of the total hip and spine [ Time Frame: At 6 month intervals over 2 years ] [ Designated as safety issue: No ]
  • Markers of bone turnover [ Time Frame: At 6 month intervals over 2 years ] [ Designated as safety issue: No ]
  • Safety (adverse events and laboratory data) and feasibility [ Time Frame: At 6 month intervals over 2 years ] [ Designated as safety issue: No ]
  • Participation and survival [ Time Frame: At 6 month intervals over 2 years ] [ Designated as safety issue: No ]
  • Fragility fractures through 12 months [ Time Frame: At 6 month intervals over 2 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • BMD at other skeletal sites [ Time Frame: At 6 month intervals over 2 years ] [ Designated as safety issue: No ]
  • Functional and cognitive assessments [ Time Frame: At 6 month intervals over 2 years ] [ Designated as safety issue: No ]
  • Comorbidity index and fragility fractures [ Time Frame: At 6 month intervals over 2 years ] [ Designated as safety issue: No ]
  • Survival after 12 months [ Time Frame: At 6 month intervals over 2 years ] [ Designated as safety issue: No ]

Enrollment: 181
Study Start Date: December 2007
Study Completion Date: February 2014
Primary Completion Date: February 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
Active Zoledronic Acid study drug group
Drug: Intravenous zoledronic acid
Intravenous zoledronic acid 5.0 mg once
Other Name: Zometa
No Intervention: 2
Placebo

Detailed Description:

This is a 2-year, randomized, double-blind, calcium/vitamin D-controlled clinical trial of a single dose of therapy with at least 12 months follow-up. All participants will receive calcium and vitamin D throughout the trial. At baseline, 190 women will be randomized in a 1:1 allocation to zoledronic acid (group 1) or zoledronic acid placebo (group 2). At the end of 24 months, women will be followed to gather data on longer term fragility fracture rates and survival until all participants have completed 24 months of follow-up.

  Eligibility

Ages Eligible for Study:   65 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • We will include elderly women 65 years and older if they reside in a nursing home or an assisted living facility and have a known history of osteoporosis, as determined by history of an adult fragility fracture or bone mineral density criteria for osteoporosis (T-score -2.5 at the total hip, femoral neck or spine) or low bone mass (T-score < -2.0 at the total hip, femoral neck or spine, consistent with the National Osteoporosis Foundation Treatment guidelines). If a participant's spine and or hip are not evaluable (due to surgery, calcifications, artifact in the scan area, scoliosis, etc.), they may be included in the study with a T-score of ≤ -2.0 at the forearm.
  • Elders will be chosen without consideration of ethnic or racial background. We chose frail, institutionalized women because 70-85% of them have osteoporosis and this age group is substantially under-treated.
  • We will include all who qualify, if they are able to weight bear or assist with transfer to chair, to endure that the results have maximum generalizability to the nursing home population as a whole.

Exclusion Criteria:

  • Children will be excluded because they are not frail, institutionalized elders.
  • Men will be excluded because they do not become postmenopausal and are less likely to become osteoporotic.
  • We will exclude institutionalized women with subacute illnesses who are not expected to survive or who will be discharged in less than 2 years.
  • We will also exclude patient with a contraindication to bisphosphonate, such as hypocalcemia, allergy, pervious adverse event (excluding gastrointestinal disorders), or currently on an oral bisphosphonate.
  • We will exclude patients with a calculated creatinine clearance of < 30 ml/mm.
  • We will exclude women scheduled for or in need of a tooth extraction as this procedure has been associated with osteonecrosis of the jaw in patients with cancer given multiple coursed of high dose intravenous bisphosphonates.
  • We will screen for these conditions by detailed history, physical exam (including dental exam), chart review, and baseline laboratory analyses, including BUN/creatinine, liver function tests, TSH, calcium, PTH, 25-hydroxyvitamin D, alkaline phosphatase and baseline calculated creatinine clearance. Participants with vitamin D levels < 20 ng/ml will be treated with vitamin D 50,000 IU/wk for 8 weeks in addition to calcium. Vitamin D will be rechecked and the patient will be enrolled if the vitamin D level is > 20 ng/ml.
  • Patients will be allowed to continue on certain medications known to affect bone and mineral metabolism (e.g. glucocorticoids, anticonvulsants) because their use is common in this population. (In our facilities, 2.9% of patients use glucocorticoids and 7.2% use anti-epileptic drugs.) In addition, women who have been treated in the past or present with osteoporosis agents, such as estrogen/progesterone, raloxifene, and calcitonin, will be allowed to participate and continue on these therapies if prescribed by their physician. However, if patients are currently on or have been on bisphosphonates for greater than 1 year in the previous 2 years prior to enrollment, they will be excluded as some bisphosphonates are long acting.
  • Patients will be allowed to wear hip pads if prescribed by their physician. If they are on parathyroid hormone, they may participate, but will be told that monotherapy with parathyroid hormone is more beneficial than combination therapy with parathyroid hormone and alendronate, as we have previously demonstrated.
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00558012

Locations
United States, Pennsylvania
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, United States, 15213
Sponsors and Collaborators
University of Pittsburgh
Investigators
Principal Investigator: Susan L Greenspan, MD University of Pittsburgh
  More Information

No publications provided

Responsible Party: University of Pittsburgh
ClinicalTrials.gov Identifier: NCT00558012     History of Changes
Other Study ID Numbers: 0612018, RO1 AG028086-01A1
Study First Received: November 13, 2007
Last Updated: February 12, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by University of Pittsburgh:
Osteoporosis
Bone loss
Frail Geriatric Women
Nursing Home Patients
Fragility Fractures

Additional relevant MeSH terms:
Fractures, Bone
Osteoporosis
Wounds and Injuries
Bone Diseases, Metabolic
Bone Diseases
Musculoskeletal Diseases
Zoledronic acid
Diphosphonates
Bone Density Conservation Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 31, 2014