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

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:

1. 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).
2. 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).
3. Leads more rapidly to improved functional outcome using a short physical performance battery to assess lower extremity function (secondary outcome).

Study Overview

• Status: Completed
• Conditions: Osteoporotic Fractures
• Intervention / Treatment: Drug: Teriparatide Prefilled Syringe; Drug: Placebo

Detailed Description

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:

1. 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).
2. 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).
3. 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.

• Study Type: Interventional
• Enrollment (Actual): 35
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10021
      • Hospital for Special Surgery

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 65 years and older (OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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:

1. Persons unable to complete the NRS and other surveys based on their mini-mental status score (≤18; consistent with moderate and severe cognitive impairment)
2. Previously (prior to fracture) non-ambulatory subjects

3. Exclusion criteria related to contraindication or intolerance to TPTD:

   1. Hypersensitivity to TPTD
   2. Patients with increased risk of osteosarcoma: Paget's disease, history of radiation exposure
   3. Patients with active hypercalcemia
   4. Current hyperparathyroidism and other metabolic bone disease including osteogenesis imperfecta
   5. History of multiple renal calculi or renal calculus within the last 2 years
   6. 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.
   7. Evidence of metastatic cancer or history of bone cancer or any active cancer other than basal or squamous cell carcinoma.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Teriparatide Prefilled Syringe; 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; TPTD 20 mcg; Other Names: Forteo
PLACEBO_COMPARATOR: Placebo; 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; Matching placebo as a prefilled syringe with all inactive ingredients; Other Names: Placebo prefilled syringe

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Hospital for Special Surgery, New York
• Collaborators: Weill Medical College of Cornell University

Publications and helpful links

General Publications

• Nieves JW, Cosman F, McMahon D, Redko M, Hentschel I, Bartolotta R, Loftus M, Kazam JJ, Rotman J, Lane J. Teriparatide and pelvic fracture healing: a phase 2 randomized controlled trial. Osteoporos Int. 2022 Jan;33(1):239-250. doi: 10.1007/s00198-021-06065-4. Epub 2021 Aug 12.

Study record dates

Study Major Dates

• Study Start (ACTUAL): May 1, 2017
• Primary Completion (ACTUAL): March 8, 2021
• Study Completion (ACTUAL): July 8, 2021

Study Registration Dates

• First Submitted: November 18, 2016
• First Submitted That Met QC Criteria: November 21, 2016
• First Posted (ESTIMATE): November 23, 2016

Study Record Updates

• Last Update Posted (ACTUAL): July 27, 2022
• Last Update Submitted That Met QC Criteria: July 26, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Keywords: healing; teriparatide; pelvic fracture
• Additional Relevant MeSH Terms: Wounds and Injuries; Leg Injuries; Femoral Fractures; Hip Injuries; Fractures, Bone; Hip Fractures; Osteoporotic Fractures; Physiological Effects of Drugs; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Teriparatide
• Other Study ID Numbers: 2015-330

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The investigators will make the data available for sharing 12-months after the publication of the primary paper. SAS datasets, a data dictionary, images of case report forms, SAS format library, the SAS program in which source data is recoded for analysis and data table summary descriptive statistics for data validation cross-check will be made available on an encrypted USB drive. A data sharing agreement is required.
• IPD Sharing Time Frame: 12 months after publication of results for 2 years
• IPD Sharing Access Criteria: Submission should be made to Nievesje@hss.edu

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No