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VERtebral Fracture Treatment Comparisons in Osteoporotic Women

Phase 4
Completed
Conditions
Postmenopausal Osteoporosis
Interventions
Registration Number
NCT01709110
Lead Sponsor
Eli Lilly and Company
Brief Summary

The primary purpose of participation in this study is to answer whether teriparatide is superior to risedronate in reducing the occurrence of new vertebral fractures during 24 months of therapy.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
Female
Target Recruitment
1366
Inclusion Criteria
  • Postmenopausal women with osteoporosis, as defined by low bone mineral density (BMD), i.e. anterior-posterior lumbar spine, total hip or femoral neck BMD ≥1.5 standard deviations below the average BMD for young, healthy, non-Hispanic, Caucasian women
  • A minimum of 2 moderate or 1 severe vertebral fragility fractures (confirmed by central reader) were required
Exclusion Criteria
  • Increased risk of osteosarcoma
  • History of unresolved skeletal diseases that affect bone metabolism
  • History of atypical subtrochanteric or diaphyseal femoral fractures
  • Abnormally high or low calcium levels
  • Abnormally high parathyroid hormone (PTH) levels
  • Severe vitamin D deficiency
  • Abnormal thyroid function not corrected by therapy
  • History of malignant neoplasms in the last 5 years
  • Active liver disease, clinical jaundice
  • Significant impairment of hepatic or renal function
  • History of nephro- or urolithiasis
  • Previous or planned kypho- or vertebroplasty
  • Active or risk for osteonecrosis of the jaw
  • Active or recent history of upper gastrointestinal disorders
  • Unable to stand or sit in the upright position for at least 30 minutes

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
TeriparatidePlaceboTeriparatide 20 microgram (µg) administered by subcutaneous (SC) injection once daily for 24 months. Placebo given orally once weekly for 24 months. Elemental Calcium 500 to 1000 milligram per day and Vitamin D 400 to 800 International Units per day, both administered orally once daily while receiving treatment.
RisedronatePlaceboRisedronate 35 milligram (mg) administered orally once weekly for 24 months. Placebo given by SC injection once daily for 24 months. Elemental Calcium 500 to 1000 milligram per day and Vitamin D 400 to 800 International Units per day, both administered orally once daily while receiving treatment.
TeriparatideCalciumTeriparatide 20 microgram (µg) administered by subcutaneous (SC) injection once daily for 24 months. Placebo given orally once weekly for 24 months. Elemental Calcium 500 to 1000 milligram per day and Vitamin D 400 to 800 International Units per day, both administered orally once daily while receiving treatment.
TeriparatideTeriparatideTeriparatide 20 microgram (µg) administered by subcutaneous (SC) injection once daily for 24 months. Placebo given orally once weekly for 24 months. Elemental Calcium 500 to 1000 milligram per day and Vitamin D 400 to 800 International Units per day, both administered orally once daily while receiving treatment.
TeriparatideVitamin DTeriparatide 20 microgram (µg) administered by subcutaneous (SC) injection once daily for 24 months. Placebo given orally once weekly for 24 months. Elemental Calcium 500 to 1000 milligram per day and Vitamin D 400 to 800 International Units per day, both administered orally once daily while receiving treatment.
RisedronateRisedronateRisedronate 35 milligram (mg) administered orally once weekly for 24 months. Placebo given by SC injection once daily for 24 months. Elemental Calcium 500 to 1000 milligram per day and Vitamin D 400 to 800 International Units per day, both administered orally once daily while receiving treatment.
RisedronateCalciumRisedronate 35 milligram (mg) administered orally once weekly for 24 months. Placebo given by SC injection once daily for 24 months. Elemental Calcium 500 to 1000 milligram per day and Vitamin D 400 to 800 International Units per day, both administered orally once daily while receiving treatment.
RisedronateVitamin DRisedronate 35 milligram (mg) administered orally once weekly for 24 months. Placebo given by SC injection once daily for 24 months. Elemental Calcium 500 to 1000 milligram per day and Vitamin D 400 to 800 International Units per day, both administered orally once daily while receiving treatment.
Primary Outcome Measures
NameTimeMethod
Proportion of Participants With New Vertebral FracturesBaseline through 24 Months

The incidence of new vertebral fractures was assessed by quantitative vertebral morphometry measurements (QM) with qualitative visual semiquantitative grading (SQ) confirmation.

A new vertebral fracture was diagnosed in a vertebra that was non-fractured at the baseline radiological examination. It was defined as a loss of vertebral body height of at least 20% and 4 mm from the baseline radiograph by vertebral QM, based upon placement of six points by a trained, central reader. Any fractures identified by QM were confirmed using SQ: if the vertebral body also had an increase of one or more severity grade, it was considered an incident vertebral fracture.

Secondary Outcome Measures
NameTimeMethod
Proportion of Participants With Pooled New and Worsening Vertebral FracturesBaseline through 24 Months

Worsening of a pre-existing fracture was considered if the decrease in vertebral height was at least one severity grade in the semi-quantitative assessment, confirmed by a trained central reader, where vertebrae were graded as normal (SQ0) or as with mild (SQ1), moderate (SQ2), or severe (SQ3) fractures, defined as \~20 to 25% (mild), \~25 to 40% (moderate) or \~40% or more (severe) decrease in anterior, central, or posterior vertebral height (T4 to L4).

Proportion of Participants With Pooled Fragility and Traumatic Non-Vertebral FracturesBaseline through 24 Months

Traumatic fractures were considered if resulting from a severe trauma such as a traffic collision, a beating, or having been struck by a falling or moving object.

Proportion of Participants With Major Non-Vertebral Fragility FracturesBaseline through 24 Months

A major non-vertebral fracture is a fracture at any of the following non-vertebral sites hip, radius, humerus, ribs, pelvis, tibia and femur. Non-vertebral fractures were determined by direct questioning at each visit, and confirmed by the site investigators by x-ray, radiology or surgical report. Fractures resulting from a severe trauma such as a traffic collision, a beating, or having been struck by a falling or moving.

Proportion of Participants With New Moderate and/or Severe Vertebral FracturesBaseline through 24 Months

Vertebrae were graded as moderate (SQ2), or severe (SQ3) fractures, based on \~25 to 40% (moderate) or \~40% or more (severe) decrease in anterior, central, or posterior vertebral height (T4 through L4).

Proportion of Participants With New Multiple (2 or More) Vertebral FracturesBaseline through 24 Months
Proportion of Participants With Pooled Clinical Vertebral and Non-Vertebral Fragility FracturesBaseline through 24 Months

A clinical vertebral fracture was defined as a new or worsening vertebral fracture, confirmed by radiography, that was associated with signs and symptoms highly suggestive of a vertebral fracture.

All non-vertebral fractures that occurred and were diagnosed between visits required the confirmation by the site investigators after evaluating the original x-ray film(s), the radiology or surgical report. For clinical vertebral fractures, the final confirmation of the diagnosis required the centralized evaluation by a trained, independent reader.

Proportion of Participants With Non-Vertebral Fragility FracturesBaseline through 24 Months

A non-vertebral fracture is a fracture at any of the following non-vertebral sites: clavicle, scapula, ribs, sternum, sacrum, coccyx, humerus, radius, ulna, carpus, pelvis, hip, femur, patella, tibia, fibula, ankle, calcaneus, tarsus, and metatarsal. Non-vertebral fractures were determined by direct questioning at each visit, and confirmed by the site investigators by x-ray, radiology or surgical report. Fractures resulting from a severe trauma such as a traffic collision, a beating, or having been struck by a falling or moving object were not considered fragility fractures but traumatic fractures.

Change From Baseline to 24 Months Endpoint in HeightBaseline, 24 Months
Change From Baseline to 24 Months Endpoint in Back Pain Using an 11-point Numerical Pain Rating ScaleBaseline, 24 Months

Participants rated the worst back pain during the 24 hours preceding the visit at baseline and each post-baseline visit. An 11-point numerical back pain rating scale (rated from 0 = no back pain to 10 = worst possible back pain) was used.

Change From Baseline to 24 Months Endpoint in the European Quality of Life Questionnaire [EQ-5D-5L] (US)Baseline, 24 Months

The EQ-5D-5L is a generic, multidimensional, health-related, quality-of-life instrument completed on five dimensions to measure health-related quality of life. The profile allowed participants to rate their health state in five health domains: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression using a five level scale (no problems, slight problems, moderate problems, severe problems, and unable to/extreme problems). The responses are used to derive the health state index scores using the United States (US) cross walk algorithm, with scores ranging from -0.11 to 1.0. A higher score indicates better health state.

Change From Baseline to 24 Months Endpoint in the European Quality of Life Questionnaire [EQ-5D-5L] (UK)Baseline, 24 Months

The EQ-5D-5L is a generic, multidimensional, health-related, quality-of-life instrument completed on five dimensions to measure health-related quality of life. The profile allowed participants to rate their health state in five health domains: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression using a five level scale (no problems, slight problems, moderate problems, severe problems, and unable to/extreme problems). The responses are used to derive the health state index scores using the United Kingdom (UK) algorithm, with scores ranging from -0.59 to 1.0. A higher score indicates better health state.

Trial Locations

Locations (1)

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

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