PTH(1-34) and Pelvic Fracture Healing - a Randomized Controlled Trial

Study Overview
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Brief Summary
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In the proposed trial the investigators will recruit women and men >65 years of age with acute osteoporosis-related pelvic fractures and address 3 specific aims over 3 months of treatment in a placebo controlled double blind study to determine if standard care and teriparatide 20 mcg/day versus placebo for pelvic fractures: Results in earlier evidence of cortical bridging on routine radiographs followed by confirmatory Focus CT, a novel method to reduce radiation exposure from CT scans (primary outcome). Leads to a faster reduction in pain as assessed by both the Numeric Rating Scale and a reduction in the use of narcotics (secondary outcome). Leads more rapidly to improved functional outcome using a short physical performance battery to assess lower extremity function (secondary outcome).

Detailed Description
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The incidence rate of pelvic fractures increases dramatically with age, from 5.4 and 3.8 per 10,000 person-years in women and men aged 65 to 69 years to 93.5 and 44.5 per 10,000 person-years in women and men aged 90 years and older, respectively. Pelvic fractures are accompanied by severe pain, chronic immobility and loss of function and independence in the elderly. Pelvic fractures consume substantial healthcare resources, and based on administrative claims data, they are one of the most costly osteoporosis related fractures. Un-healed fractures, occurring in one-third of pelvic fracture patients at 3 months, can cause continued pain and impact mobility. With aging of the population, and expected concomitant increase in the incidence of pelvic fractures, there is a pressing need to find effective treatments that will accelerate healing. Fracture of the pubic ramus is most relevant and practical for randomized double-blinded placebo controlled study as this fracture is accompanied by severe pain and immobility in elderly, is associated with delayed fracture healing, and is almost always treated non-operatively. The current standard of care for pelvic fractures includes pain management, patient mobilization, and the prevention of complications associated with comorbid conditions. The investigators hypothesize that development of a successful adjunctive therapy to accelerate fracture healing would lead to improved care and reduce both direct and indirect costs from pelvic fractures. In the proposed trial the investigators will recruit women and men >65 years of age with acute osteoporosis-related pelvic fractures and address 3 specific aims over 3 months of treatment in a placebo controlled double blind study to determine if standard care and teriparatide 20 mcg/day versus placebo for pelvic fractures: Results in earlier evidence of cortical bridging on routine radiographs followed by confirmatory Focus CT, a novel method to reduce radiation exposure from CT scans (primary outcome). Leads to a faster reduction in pain as assessed by both the Numeric Rating Scale and a reduction in the use of narcotics (secondary outcome). Leads more rapidly to improved functional outcome using a short physical performance battery to assess lower extremity function (secondary outcome). The investigators will extend this study with 9 months of open label TPTD to determine if any potential differences between the placebo and TPTD groups during the 3 months of treatment are evident and persist over time, even in patients who use TPTD after the three month placebo controlled intervention. If TPTD can improve fracture healing, this study will have an impact on the treatment of persons with pelvic fracture who are not surgical candidates and often face severe pain, chronic immobility, and loss of function in the elderly. A positive finding of accelerated healing of pelvic fractures would also encourage study of TPTD for treatment of other osteoporotic fractures.

Official Title
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PTH(1-34) and Pelvic Fracture Healing - a Randomized Controlled Trial

Conditions
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Osteoporotic Fractures

Intervention / Treatment
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* Drug: Teriparatide Prefilled Syringe
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Postmenopausal women and men >65 years of age with acute pelvic fractures, occurring with minimal trauma, presenting to Helen Hayes Hospital, Hospital for Special Surgery, or New York Hospital (Cornell Medical). Patients that have either one or multiple pelvic fractures or sacral and pelvic fractures will be included in the study. Subjects must start treatment within one month of hip fracture. Exclusion Criteria: Persons unable to complete the NRS and other surveys based on their mini-mental status score (≤18; consistent with moderate and severe cognitive impairment) Previously (prior to fracture) non-ambulatory subjects Exclusion criteria related to contraindication or intolerance to TPTD: Hypersensitivity to TPTD Patients with increased risk of osteosarcoma: Paget's disease, history of radiation exposure Patients with active hypercalcemia Current hyperparathyroidism and other metabolic bone disease including osteogenesis imperfecta History of multiple renal calculi or renal calculus within the last 2 years Normal alkaline phosphatase levels will not be used as an entrance criterion because most fracture patients will have elevations due to the acute fracture. However, the investigators will attempt to obtain lab tests from the period prior to fracture to determine if they were normal. If unexplained elevations in alkaline phosphatase are found in labs prior to the fracture we will exclude that subject. Evidence of metastatic cancer or history of bone cancer or any active cancer other than basal or squamous cell carcinoma.

Ages Eligible for Study
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Minimum Age: 65 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
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Teriparatide Prefilled Syringe<br>TPTD is supplied as a sterile, colorless, clear, isotonic solution in a glass cartridge which is pre-assembled into a disposable delivery device (pen) for subcutaneous injection. Each prefilled delivery device is filled with 2.7 mL to deliver 2.4 mL. Each mL contains 250 mcg teriparatide (corrected for acetate, chloride, and water content), 0.41 mg glacial acetic acid, 0.1 mg sodium acetate (anhydrous), 45.4 mg mannitol, 3 mg Metacresol, and Water for Injection. In addition, hydrochloric acid solution 10% and/or sodium hydroxide solution 10% may have been added to adjust the product to pH 4. | Drug: Teriparatide Prefilled Syringe<br>* TPTD 20 mcg<br>* Other names: Forteo;|
| Placebo Comparator: Placebo<br>Placebo is supplied as a sterile, colorless, clear, isotonic solution in a glass cartridge which is pre-assembled into a disposable delivery device (pen) for subcutaneous injection. Each prefilled delivery device is filled with 2.7 mL to deliver 2.4 mL. Each mL contains 0.41 mg glacial acetic acid, 0.1 mg sodium acetate (anhydrous), 45.4 mg mannitol, 3 mg Metacresol, and Water for Injection. In addition, hydrochloric acid solution 10% and/or sodium hydroxide solution 10% may have been added to adjust the product to pH 4. | Drug: Placebo<br>* Matching placebo as a prefilled syringe with all inactive ingredients<br>* Other names: Placebo prefilled syringe;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Evidence of Cortical Bridging for Fracture Healing | Evidence of cortical bridging based on Focus CT, | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Pain by Numeric Rating Scale Between Baseline and Three Months | Leads to a faster reduction in pain as assessed by the Numeric Rating Scale of 0 (no pain) to 10 (worst pain). The mean reduction in pain score from 0 to 3 months is reported. Higher scores mean a greater reduction in pain. | 3 months | 
| Functional Outcome Using a Battery That Includes Walking Speed, Repeated Chair Stands, and Balance at 3 Months | More rapidly improved functional outcome using a short physical performance battery to assess lower extremity function (walking speed, repeated chair stands, and balance) at 3 months. Scale is 0 to 100 with higher scores indicating better physical performance. | 3 months | 
| Physical Function at 12 Months Using a Battery That Includes Walking Speed, Repeated Chair Stands, and Balance | More rapidly improved functional outcome using a short physical performance battery to assess lower extremity function (walking speed, repeated chair stands, and balance) at 12 months. Scale is 0 to 100 with higher scores indicating better performance. | 12 months | 
| Pain at 12 Months Based on the Numeric Rating Scale | Pain at 12 months as assessed by the Numeric Rating Scale (0 to 10 where 0 means no pain and 10 worst pain) | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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healing, pelvic fracture, teriparatide