Abstract
BACKGROUND: Non-unions, defined as fractures not healed after at least 6 months, are a multifactorial complication occurring in 2-10% of all fractures and in up to 30% of patients with certain risk factors. Treatment costs are markedly higher than those associated with normal fracture healing and patients often suffer from pain and loss of function. Surgical revision is the gold standard for treatment; however, the disadvantages are re-hospitalization, possible secondary diseases and side effects such as post-operative infections, complications of anesthesia and embolisms. Low-intensity pulsed ultrasound (LIPUS) is a low-risk procedure, with skin reactions being the only side effect experienced by a very small number of patients. Patients can use the treatment independently at home, eliminating the need for repeated hospital visits. This study aims to show that LIPUS treatment is not inferior to surgical intervention by a threshold of -25 percentage points in terms of fracture healing in non-unions of the upper or lower extremity. METHODS: PiNGUin will be a five-year national, prospective, controlled, randomized, open-label, multicenter study with a medical device. Patients are randomized into one of two groups: patients in the intervention group will receive daily 20-min LIPUS treatment for 200 days or undergo standard surgical intervention in the control group. Follow-up for both groups will be 12 months. The primary endpoint is fracture healing 12 months after treatment start, defined as bony consolidation of at least 3 out of 4 cortices and functional recovery. Secondary endpoints include time to fracture healing and to full weight bearing, incidence and intensity of pain, functional complaints/activities of daily living, health-related quality of life, complications, adverse events, re-operations or re-osteosyntheses and (re-) hospitalizations, hospital stays, duration and reasons for inability to work. With a one-sided significance level of 2.5%, a power of 90% and an assumed drop-out rate of 10% 184 patients will be required per treatment group. DISCUSSION: As LIPUS is a low-complication procedure with good results to date, this treatment is considered a potential alternative to surgery. If non-inferiority is proven, patients will have a choice of both invasive and non-invasive procedures in the future. TRIAL REGISTRATION: DRKS00034357 (German Clinical Trials Register, registered March 11th, 2025).