Non-operative treatment versus reverse total shoulder prosthesis in patients aged 65–85 – a prospective, single-blinded, randomized controlled, multi-centre and multi-national trial for displaced proximal humeral fractures.

Background and Aim

Osteoporosis poses an important medical challenge worldwide, and especially for our Nordic healthcare, as it correlates positively with high age. Patients with osteoporosis frequently suffer from fractures, resulting in pain and discomfort for the individual, as well as a great burden for the healthcare system and costs for society. According to the UN Population Division, the age of the world population is rising and thereby also the incidence of fractures in the elderly. The highest incidence is in persons older than 80 years, and the Nordic population has the highest incidence of osteoporotic fractures in the world.

Typical osteoporotic fracture types are femoral neck, vertebral compression, distal radius and proximal humerus (PHF) fractures, the last of which are often referred to as shoulder fractures. Although there exists a guideline for best practice concerning the treatment of femoral neck and distal radius fractures, no such recommendation has been established for displaced PHF in adults, and the choice of treatment is still under debate. While there are several randomized controlled trials (RCT) for femoral neck and distal radius fractures, the highest level of evidence for PHF is very sparse and mainly comes from the Nordic countries.

Based on the Nordic experience of running RCTs for PHF and the high incidence of osteoporotic fractures in our countries, the NITEP collaboration was established some years ago (Nordic Innovative Trial to Evaluate osteoPorotic Fractures, http://nitep.eu/en/team/).

Given the lack of evidence for operative treatment of displaced PHF in adults and the fact that most of the previous RCTs have been performed in the Nordic countries, further research in this field was called for, and a protocol for a new trial, including all the Nordic countries, was written. The Nordic DeltaCon Trial is a single blinded multi-centre RCT comparing two treatments: non-operative versus operative treatment with the popular reverse total shoulder prosthesis, sometimes called Delta prosthesis.
The short name “DeltaCon” comes from Delta prosthesis and Conservative (non-operative) treatment.

This trial fills the urgent knowledge gap concerning a rapidly increasing method used to treat proximal humerus fractures: reverse prosthesis. The expected impact of this project for future patient care is that the planned enrolment of 150 participants will be added to the current approx. 500 patients from different RCTs in the last Cochrane update from 2015. This number of patients will add new knowledge to existing evidence.

In addition, there is no evidence for one of the most frequently used surgical methods, namely the reverse total shoulder arthroplasty (RTSA). No such patients are included in the Cochrane population of PHFs. Recently, only a small RCT from 2014 has been published, with 30 RTSA vs. 30 anatomical hemi-prosthesis patients, concluding that RTSA had a better outcome. As far as the most interesting comparison, namely surgery with RTSA versus non-operative treatment, no studies exist, to our knowledge.

Several thousand surgical procedures with RTSA have been performed in the last 10 years in Europe. In Sweden alone, 222 operations were performed in 2014–15, increasing from 46 operations in 2012–13. Therefore, the updated knowledge provided by the results of this trial may change surgical practice and allow patients to gain more quality-adjusted life years.

In the Nordic DeltaCon trial, all decliners are also asked for written permission to collect data at the 3- and 12-month follow-up to obtain information about the external validity of the trial, and whether the results can thus be generalized to all patients with this type of fracture within our defined age group.

The hypothesis of the trial is that RTSA produces a better functional outcome and less pain compared with non-operative treatment at two years.

The trial will be conducted in four Nordic countries: Norway (from 1 October 2018) and Finland, Denmark and Sweden (from spring 2019). The difference in timeline is due to an ongoing trial on PHF in these countries, which is based on a different scientific question and is expected to be completed in spring 2019.
The main research parties are the Tampere University Hospital, Finland (the main researchers are Antti Launonen and Ville Mattila) in collaboration with the Oslo University Hospital, Ullevål, Oslo, Norway (Tore Fjalestad).

All four countries will have a local, national chapter to secure the smooth progress of the trial: local meetings for all participating hospitals, a common guideline for the treatment and rehabilitation of patients and physiotherapists using our national website for former trials.

Outcomes

The primary outcome is Quick-DASH (the short form of Disabilities of the arm, shoulder and hand, DASH) at two years (short-term follow-up).
Secondary outcomes are Quick-DASH at one year and five years (medium-term follow-up). At one, two and five years, general Visual Analogue Scale (VAS) for pain, grip strength, Oxford Shoulder Score (OSS), Constant Score (CS), Quality of life assessed with the 15D score, cost analysis and calculation of quality-adjusted life years (QALYs) as well as complications in the treatment are secondary outcomes. Radiographic analysis is also a secondary outcome.

The primary and secondary outcomes are based on our former experience of similar trials and are validated scores in the field of shoulder trials. The parts with patient involvement use patient preferences according to interviews.

The study design is a superiority, single-blinded, multi-centre and multi-national randomized controlled trial between different treatments for displaced PHF. The trial is registered at www.clinicaltrials.gov with the trial identification number NCT03531463.

Participants, Organization and Collaborators

The steering committee is composed of researchers from the NITEP group (Head Prof. Ville Mattila, main researcher in Finland MD, PhD Antti Launonen, both in Tampere; and in Norway, MD, PhD Tore Fjalestad). All data will be collected on a central server in the Tampere University Hospital in Tampere, Finland.
All national chapters involve one coordinating orthopaedic surgeon / researcher and a project research physiotherapist. There will be a responsible orthopaedic surgeon and a physiotherapist representing each participating hospital.
All attending doctors and physiotherapists at the different hospitals have been given pre-trial instruction to guarantee a similar follow-up method of the randomized patients.
The outcomes will be collected online and sent to the central server in Tampere after approval from the hospital patient safety department.

The attending main researchers are the most experienced experts in their field, and thus the Nordic collaboration possesses a high level of academic knowledge in this field for running this large multicentre RCT.
There are PhD students working in this collaboration and project, and the Norwegian chapter will have one PhD student as well.