PROactive HEALing in High-Risk Pelvic and Non-hip Lower Extremity Fragility Fractures (PRO HEAL Pilot)

Status

Not yet recruiting

Phase

Phase 1/2

Enrollment

54 participants (estimated)

Sponsor

University of Calgary · Other

Design

Randomized · Single masking

Countries

1 country

Canada

Start

15 Mar 2027 (estimated)

Primary completion

16 Dec 2030 (estimated)

Completion

17 Mar 2031 (estimated)

First posted

12 Mar 2024

Last update posted

6 Oct 2026

Conditions

Lower Extremity Fractures · Pelvis · Acetabulum

Fragility fractures are common in older adults with weakened bone. At least 1 in 3 females and 1 in 5 males will sustain a fragility fracture in their lifetime, and over 80% of fractures in Canadians aged 50 years and older are attributable to osteoporosis. Fractures of the pelvis, acetabulum and lower extremity in this population are associated with delayed healing, loss of reduction, implant failure and the need for secondary surgery. Reported complication rates range from 21.5% to 40%. Efforts to improve outcomes have focused on surgical fixation technique; there is currently no pharmacological treatment given to promote healing of the fracture itself. Teriparatide is a recombinant form of parathyroid hormone (1-34) that stimulates new bone formation. It is authorized in Canada for the treatment of severe osteoporosis. Its use to promote acute fracture healing is investigational and is not an approved indication. Pre-clinical studies have demonstrated enhanced fracture callus formation and improved mechanical strength of healing bone. Clinical evidence in acute fracture healing is limited and mixed: a randomized trial in distal radius fractures reported a shorter time to cortical bridging, and systematic reviews report positive signals in delayed union and non-union, while a small phase 2 trial in acute pelvic fracture found no difference in radiographic healing at three months, although physical performance improved. That trial was terminated early following withdrawal of study drug supply, leaving it underpowered, and its authors concluded that a larger randomized trial is warranted. No randomized controlled trial has evaluated Teriparatide for the promotion of fracture healing across pelvic, acetabular and non-hip lower extremity fragility fractures in high-risk older adults. Before such a trial can be designed and appropriately powered, its feasibility must be established. PRO HEAL Pilot is a prospective, open-label, randomized controlled pilot trial with blinded outcome assessment. Fifty-four participants will be randomized 1:1 to Teriparatide or a no-treatment control. Recruitment is planned over 18 months at the Foothills Medical Centre in Calgary. Eligible participants are males and females aged 50 years and older who have sustained a low-energy fragility fracture (a fall from five feet or less) of the pelvis, the acetabulum, or the non-hip lower extremity, and who have at least one additional risk factor for delayed fracture healing: diabetes, renal dysfunction, steroid use, current or past smoking, peripheral neuropathy, or peripheral vascular disease. Fractures may be managed operatively or non-operatively. Participants must be able and willing to self-administer daily subcutaneous injections, or have a caregiver able to do so. Participants randomized to the treatment arm receive Teriparatide 20 mcg by subcutaneous injection once daily for 90 doses, with the first dose administered within five days of randomization and within 21 days of the initial fracture. Participants randomized to the control arm receive no study medication and continue standard clinical care. All participants in both arms receive a single oral loading dose of 50,000 IU vitamin D at randomization, with calcium supplementation or dietary modification to achieve a total daily intake of approximately 1,000 mg. The primary outcome is feasibility, measured as the mean number of participants recruited per month and assessed against a priori progression criteria. Secondary feasibility outcomes are treatment fidelity, defined as the proportion of participants receiving 80% or more of the trial medication; participant retention; consent rate; and barriers to trial implementation. Clinical, functional and value-based outcomes will be collected in the same manner as planned for the full-scale trial and reported descriptively. Clinical outcomes include pain, radiographic fracture union, unplanned surgical intervention related to the index fracture, bone mineral density, and 90-day all-cause mortality. Functional outcomes include physical performance, the Olerud Molander Score, PROMIS Mobility, and weightbearing status. Value-based outcomes include healthcare costs, quality of life, length of acute hospital stay, and re-admission. Participants are followed for six months from randomization, with study visits at 2 weeks, 6 weeks, 12 weeks and 6 months, aligned with routine post-fracture clinical follow-up. Participants receiving Teriparatide are contacted weekly by telephone during the treatment period for adherence and safety monitoring, and serum calcium is measured at every study visit. Clinical outcomes are adjudicated by independent assessors blinded to treatment allocation. This pilot trial is not powered to detect a difference in clinical efficacy between treatment arms. Its purpose is to determine whether a definitive, full-scale randomized controlled trial is feasible, and to inform its design and sample size.

• Experimental

  Teriparatide

  20 µg subcutaneous Teriparatide injection once daily for 3 months in the post-operative ankle fracture population.

• No intervention

  Non-treatment

  No treatment control arm

1. Participant recruitment rate

   Time frame · 2 years

   Registry description

   Estimate of the mean monthly recruitment rate