The Effect of Teriparatide on Bone Union in Unstable Intertrochanteric Fracture Patients Treated With PFNA

Study Overview
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Brief Summary
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Phase III, prospective, randomized, parallel, double blind, placebo-controlled study to determine whether Teriparatide can accelerate bone healing in unstable intertrochanteric fracture patients treated with Proximal Femoral Nail Antirotation (PFNA) assessed by radiographic and clinical outcomes.

Detailed Description
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Patients will undergo screening assessment to determine the eligibility for study participation and will be randomized in 1:1 ratio to receive Teriparatide 20 μg or placebo subcutaneous once daily for 12 weeks. All patients will receive supplements of 1000 mg/day of elemental calcium and 20,000 IU/week of vitamin D2. Patients will be scheduled to clinic visit for radiographic and clinical assessment at 2, 6,12 and 24 weeks postoperatively. Each participant will be in the study for 6 months in total.

Official Title
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A Phase III, Randomized, Double Blind, Placebo Controlled Study to Evaluate the Effect of Teriparatide on Bone Union in Unstable Intertrochanteric Fracture Patients Treated With Proximal Femoral Nail Antirotation (PFNA)

Conditions
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Unstable Intertrochanteric Fracture

Intervention / Treatment
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* Drug: Teriparatide
* Drug: Placebo
* Dietary Supplement: Calcium supplement
* Dietary Supplement: Vitamin D


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female patient, age ≥ 50 years at the time of screening Unstable intertrochanteric fracture (AO/OTA 31-A2 and 31-A3) Treated by proximal femoral nail antirotation (PFNA) Exclusion Criteria: Known hypersentivity to teriparatide or any form of PTH or analogue Metabolic bone disease other than primary osteoporosis (including Hyper Parathyroidism and Paget's disease of bone) Increased baseline risk of osteosarcoma (Paget's disease of the bone, previous primary skeletal malignancy, or skeletal exposure to therapeutic irradiation) History of malignant neoplasm in the 5 years prior to the study (with the exception of superficial basal cell carcinoma or squamous cell carcinoma) and carcinoma in situ of the uterine cervix treated less than 1 year prior to the study. Pre-existing of hypercalcemia (total serum calcium >10.5 mg/dL or 2.6 mmol/L) Abnormally elevated serum intact parathyroid hormone at screening (serum PTH > 70 pg/mL) Severe vitamin D deficiency (25-hydroxyvitamin D < 12 ng/mL) Unexplained elevations of alkaline phosphatase (ALP > 120 UL) Severe renal impairment (CrCL < 30 mL/min) Current treatment with digoxin and necessary to continue use during the study Concurrent treatment with oral bisphosphonates, selective estrogen receptor modulator (SERMs), calcitonin, estrogen (oral, transdermal, or injection), progestin, estrogen analog, estrogen agonist, estrogen antagonist or tibolone, and active vitamin D3 analogs. (Previous treatment is allowed but must be discontinued at screening) Previous treatment with strontium ranelate for any duration, intravenous bisphophonates within 12 months prior to the screening date, and/or denosumab within 6 months prior to the screening. Previous treatment with teriparatide, PTH or other PTH analogs, or prior participation in any other clinical trial studying teriparatide, PTH or other PTH analogs

Ages Eligible for Study
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Minimum Age: 50 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: The patients will be randomized in 1:1 ratio to receive Teriparatide or placebo
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Teriparatide<br>Teriparatide 20 μg subcutaneous once daily for 12 weeks | Drug: Teriparatide<br>* Teriparatide 20 μg subcutaneous once daily for 12 weeks (Patient self administration at home by pen injector)<br>* Other names: r-Human parathyroid hormone;Dietary Supplement: Calcium supplement<br>* 1000 mg/day of elemental calcium<br>Dietary Supplement: Vitamin D<br>* 20,000 IU/week of vitamin D2<br>|
| Placebo Comparator: Placebo<br>Placebo subcutaneous once daily for 12 weeks | Drug: Placebo<br>* Placebo subcutaneous once daily for 12 weeks. (Patient self administration at home by pen injector)<br>Dietary Supplement: Calcium supplement<br>* 1000 mg/day of elemental calcium<br>Dietary Supplement: Vitamin D<br>* 20,000 IU/week of vitamin D2<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to healing assessed by radiographic evidence | Fracture is judged to be healed radiographically if bridging callus was evident on 3 of 4 cortices as seen on two views (cortical bridging of three cortices) | from randomization, assessed up to 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical evidence of healing assessed by Harris Hip Score as one of functional outcomes | Harris Hip Score (90-100: Excellent, 80-89: Good, 70-79: Fair, <70 poor) | from randomization, assessed up to 24 months | 
| Clinical evidence of healing assessed by weight bearing ability as one of functional outcomes | Weight bearing ability (Non weight bearing, Partial weight bearing, Full weight bearing) | from randomization, assessed up to 24 months | 
| Clinical evidence of healing assessed by walking ability as one of functional outcomes | Walking ability (Independent walking, Assisted walking, Bedridden) | from randomization, assessed up to 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Terriparatide, bone fracture healing, PFNA