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

NCT ID: NCT02972424

Last Updated: 2022-07-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 35 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-05-01
• Study Completion Date: 2021-07-08

Brief Summary

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).

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.

Conditions

Osteoporotic Fractures

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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.

Group Type: EXPERIMENTAL

Teriparatide Prefilled Syringe

Intervention Type: DRUG

TPTD 20 mcg

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.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Matching placebo as a prefilled syringe with all inactive ingredients

Interventions

Teriparatide Prefilled Syringe

TPTD 20 mcg

Intervention Type: DRUG

Placebo

Matching placebo as a prefilled syringe with all inactive ingredients

Intervention Type: DRUG

Other Intervention Names

Forteo; Placebo prefilled syringe

Eligibility Criteria

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

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.

• Minimum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Weill Medical College of Cornell University

OTHER

Sponsor Role: collaborator

Hospital for Special Surgery, New York

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jeri W Nieves, PhD

Role: PRINCIPAL_INVESTIGATOR

Hospital for Special Surgery, New York

Locations

Hospital for Special Surgery

New York, New York, United States

Countries

United States

References

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.

Reference Type: RESULT

PMID: 34383100 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

2015-330

Identifier Type: -

Identifier Source: org_study_id