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

NCT02972424 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: 2015-330
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

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

Conditions

Osteoporotic Fractures

Keywords

pelvic fracture; healing; teriparatide

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Evidence of Cortical Bridging for Fracture Healing

  Evidence of cortical bridging based on Focus CT,

  3 months

Secondary Outcomes (4)

• Change in Pain by Numeric Rating Scale Between Baseline and Three Months

  3 months

• Functional Outcome Using a Battery That Includes Walking Speed, Repeated Chair Stands, and Balance at 3 Months

  3 months

• Physical Function at 12 Months Using a Battery That Includes Walking Speed, Repeated Chair Stands, and Balance

  12 months

• Pain at 12 Months Based on the Numeric Rating Scale

  12 months

Study Arms (2)

Teriparatide Prefilled Syringe

EXPERIMENTAL

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

Placebo

PLACEBO COMPARATOR

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

Interventions

Teriparatide Prefilled Syringe DRUG

TPTD 20 mcg

Also known as: Forteo

Teriparatide Prefilled Syringe

Placebo DRUG

Matching placebo as a prefilled syringe with all inactive ingredients

Also known as: Placebo prefilled syringe

Placebo

Eligibility Criteria

• Age: 65 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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
• 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.

Sponsors & Collaborators

• Hospital for Special Surgery, New York: lead
• Weill Medical College of Cornell University: collaborator

Study Sites (1)

Hospital for Special Surgery

New York, New York, 10021, United States

Location

Related Publications (1)

• 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.

  PMID: 34383100 RESULT

MeSH Terms

Conditions

Osteoporotic Fractures; Hip Fractures

Interventions

Teriparatide

Condition Hierarchy (Ancestors)

Fractures, Bone; Wounds and Injuries; Femoral Fractures; Hip Injuries; Leg Injuries

Intervention Hierarchy (Ancestors)

Parathyroid Hormone; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins

Limitations and Caveats

This trial had several limitations. The first is that we were underpowered to find an effect of TPTD on radiographic evidence of fracture healing due to a halt in supply of study medication, therefore, our findings should be considered exploratory. Recruitment was difficult; we screened 363 patients to recruit 35 subjects. It is also difficult to retain an older cohort with multiple underlying comorbidities. We only assessed healing at one time point.

Results Point of Contact

• Title: Dr. Jeri W. Nieves
• Organization: Hospital for Special Surgery

nievesje@hss.edu

2126061604

Study Officials

• Jeri W Nieves, PhD

  Hospital for Special Surgery, New York

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 18, 2016
• First Posted: November 23, 2016
• Study Start: May 1, 2017
• Primary Completion: March 8, 2021
• Study Completion: July 8, 2021
• Last Updated: July 27, 2022
• Results First Posted: July 27, 2022

Record last verified: 2022-07

Data Sharing

• IPD Sharing: Will share
• Time Frame: 12 months after publication of results for 2 years
• Access Criteria: Submission should be made to Nievesje@hss.edu

Locations

US (1)