## Protocol Section
### Identification Module
**NCT ID:** NCT06416618

**Acronym:** PHF50-65

**Brief Title:** Surgical Versus Non-surgical Treatment of Displaced Proximal Humerus Fracture in Adults Aged 50 to 65 Years

**Official Title:** Surgical Versus Non-surgical Treatment of Displaced Proximal Humerus Fracture in Adults Aged 50 to 65 Years: a Pragmatic Randomized Controlled Trial

#### Organization Study ID Info
**ID:** PHF5065
#### Organization
**Class:** OTHER
**Full Name:** Zealand University Hospital
### Status Module
#### Completion Date
**Date:** 2028-12-31

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-05-20

**Type:** ACTUAL

**Last Update Submit Date:** 2024-05-16

**Overall Status:** NOT_YET_RECRUITING

#### Primary Completion Date
**Date:** 2027-12-31

**Type:** ESTIMATED

#### Start Date
**Date:** 2024-05-15

**Type:** ESTIMATED

**Status Verified Date:** 2024-05

#### Study First Post Date
**Date:** 2024-05-16
**Type:** ACTUAL
**Study First Submit Date:** 2024-05-08
**Study First Submit QC Date:** 2024-05-14
### Sponsor Collaborators Module

#### Collaborators

**Class:** OTHER

**Name:** Tampere University Hospital

#### Lead Sponsor

**Class:** OTHER

**Name:** Zealand University Hospital

#### Responsible Party

**Investigator Affiliation:** Zealand University Hospital

**Investigator Full Name:** Line Lojbert Houkjaer

**Investigator Title:** Principal Investigator, M.D.

**Type:** PRINCIPAL_INVESTIGATOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** False

**Oversight Has DMC:** True

### Description Module

**Brief Summary:** The goal of this clinical trial is to study whether surgery results in better functional outcomes than non-surgical treatment among patients aged 50-65 with a displaced proximal humerus fracture.

The main questions it aims to answer are:

• Does osteosynthesis result in better patient-reported functional outcomes compared to non-surgical treatment at 12 months follow-up?

Aim is also to characterize the patient group aged 50-65 regarding fracture morphology, osteoporosis, and clinical frailty scale.

The study compare operation with either plate or nail fixation to non-surgical treatment.

Participants will:

* Receive either surgical treatment or non-surgical treatment.
* At 6 months, 1 year, and 2 years, the patient will answer two short questionnaires (Oxford Shoulder Score and Eq-5D-3L).

The primary outcome will be Oxford Shoulder Score at 12 months. The secondary outcome will be OSS at 6 and 24 months and EQ-5D-3L score measured at the same time-points. Adverse events and conversion to surgery will be registered. OSS and EQ-5D-3L will be completed just before the 6 months visit.

**Detailed Description:** Proximal humerus fractures (PHF) are common injuries. At the age of 60 and above, no clinically important difference between surgical and non-surgical treatment after one year has been reported based on a recent Cochrane review of 10 trials.

The treatment of choice for displaced PHF in adults 50-65 years is anatomical reconstruction, and osteosynthesis if possible, which is why many patients in this age group with a displaced PHF undergo surgical treatment.

Orthopaedic surgeons may encounter challenges in guiding patients and formulating treatment strategies within specific age groups due to the absence of inclusion of this younger patient demographic in existing evidence. Knowledge is primarily derived from studies on the population aged 60 years and above. There exists an intermediate age group of patients for whom it remains uncertain whether the benefits and harms of non-surgical and surgical interventions are comparable

This trial is a two-center, parallel-group, randomized, superiority trial comparing osteosynthesis with non-surgical treatment following a displaced proximal humerus fractures in patients aged 50-65 years. The participants will be included and allocated equally to surgical treatment with osteosynthesis (comparator) with non-surgical treatment (intervention).

The surgical group will visit the outpatient clinic after 2, 12, and 24 weeks, while the non-surgical group will visit after 6, (12) and 24 weeks. X-rays will be obtained before every visit.

Both groups will be referred to rehabilitation in the municipalities.

Without a patient-derived MCID for PHF, a relevant difference of 9,6 was assumed to represent clinically meaningful difference. This is equivalent to approximately a 20 % difference between the surgical group and the non-surgical group on a 0-48 OSS scale. With a power of 80% and a 5% level of significance, a sample size of 25 participants per group is required. Assuming a 15 % loss to follow-up, the recruitment target is 30 patients in each group, meaning 60 participants overall.

In case of treatment failure in either group, defined as persistent pain or a failed osteosynthesis, a salvage procedure with secondary osteosynthesis or a reverse shoulder arthroplasty (RSA), will be offered.

Additionally, there are plans for a systematic collection of reasons for non-inclusion of eligible patients who were not recruited into the trial (decliner cohort), and their baseline characteristics, treatment preferences. The decliner cohort will receive the same treatment, follow-up, and outcome measurements as the included patients.

Statistical analysis:

For the primary outcome, a two-sample t-test will be used. P-value \< 0.05. For secondary outcome - considering the hierarchical nature of the data - clustered and repeated measure data - linear mixed models will be utilized for the statistical analysis.

Salvage procedures and adverse events will be reported descriptively. Reoperation in the form of amotio will be considered a complication and, therefore, not included in the statistics of salvage procedures. The time of salvage procedures in both groups will be recorded and analysed using the Cox proportional hazard model

As suggested in the extension of the CONSORT 2010 statement, the primary endpoints will be analysed for the intention-to-treat (ITT) population and, for sensitivity reasons, for the per-protocol (PP) population. There will be two analyses for both ITT and PP populations: one including salvage procedures and one excluding them. These analyses will be used to evaluate the occurrence of salvage procedures and the intervention's effect.

The length of rehabilitation will be presented with a mean and standard division for each of the groups. Differences in adherence to rehabilitation within the groups will be reported using the chi-squared test. Linear mixed models will be employed to test whether adherence to rehabilitation modifies the effect of the groups.

All statistical analyses will also be conducted for the decliner cohort, including a comparison of the primary outcome between those with a preference for surgical treatment and those with a preference for non-surgical treatment

### Conditions Module

**Conditions:**

- Proximal Humeral Fracture

- Shoulder Fractures

### Design Module

#### Design Info

**Allocation:** RANDOMIZED

**Intervention Model:** PARALLEL

**Intervention Model Description:** The study is a two-center, parallel-group, randomized, superiority trial

##### Masking Info

**Masking:** SINGLE

**Masking Description:** The primary investigator will conduct the blinded statistical analysis through data anonymization and will be supervised by a biostatistician. After the blinded statistical analysis has been completed, two abstracts will be written based on the pre-blinding analysis results before the blinding is revealed.

**Who Masked:**

- OUTCOMES_ASSESSOR

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 60

**Type:** ESTIMATED

**Phases:**

- NA

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** Patients in the non-surgical group will be offered an optional sling for comfort for an additional 1-2 weeks at their first visit,

**Intervention Names:**

- Procedure: Non surgical

**Label:** Non-surgical treatment

**Type:** EXPERIMENTAL

#### Arm Group 2

**Description:** The surgical group will receive osteosynthesis with a locking plate or an intramedullary locking nail, according to the surgeon's choice

**Intervention Names:**

- Procedure: Surgical

**Label:** Procedure: Surgical treatment

**Type:** ACTIVE_COMPARATOR

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Procedure: Surgical treatment

**Description:** Surgical group: After osteosynthesis, they will be provided with a sling and swathe immediately after the surgery. From the first postoperative day, only the sling will be used. Two weeks postoperatively, patients will undergo clinical and radiological follow-up in the outpatient clinic. They will be referred to post-operative rehabilitation in the municipalities. At 12 weeks postoperatively, patients will have another clinical and radiological follow-up. This is the current standard care for surgical treatment with a plate or intramedullary nail.

**Name:** Surgical

**Type:** PROCEDURE

#### Intervention 2

**Arm Group Labels:**

- Non-surgical treatment

**Description:** Non-surgical group: Patients in the non-surgical group will be offered an optional sling for comfort for an additional 1-2 weeks at their first visit, 10-14 days post-injury. Patients will be referred to rehabilitation in the municipalities. At week 6 post-injury, all patients will undergo clinical and radiological follow-up. This represents the current standard care for non-surgical treatment of displaced PHF at the departments.

**Name:** Non surgical

**Type:** PROCEDURE

### Outcomes Module

#### Primary Outcomes

**Description:** Oxford Shoulder Score is a patient-reported shoulder-specific outcome measure. It is a patient-administrated questionnaire to assess shoulder function. It consists of 12 questions on a 5-point Likert scale (both pain- and function-related), each offering five ordinal response options. The cumulative score ranges between 0 and 48, being 0 (worst) to 48 (best: no pain or no functional limitation).

**Measure:** Oxford Shoulder Score 12 months

**Time Frame:** 12 months

#### Secondary Outcomes

**Description:** Oxford Shoulder Score is a patient-reported shoulder-specific outcome measure. It is a patient-administrated questionnaire to assess shoulder function. It consists of 12 questions on a 5-point Likert scale (both pain- and function-related), each offering five ordinal response options. The cumulative score ranges between 0 and 48, being 0 (worst) to 48 (best: no pain or no functional limitation).

**Measure:** Oxford Shoulder Score

**Time Frame:** 6 and 24 months

**Description:** Q-5D-3L is a generic health-related quality-of-life assessment tool. It consists of a 5-dimension descriptive questionnaire about mobility, self-care, usual activities, pain/discomfort, and anxiety/depression as a measure for health-related quality of life. Each dimension has 3 levels: No problems, some/moderate problems and unable/extreme problems. Each dimension is weighted differently and results in a total score based on the EQ-5D index calculator (TTO). The EQ-5D-3L also includes an overall scale (numeric rating scale) in which patient rates overall health condition today on a scale between 1 - 100, with 100 being the highest level of health imaginable

**Measure:** EQ-5D-3L

**Time Frame:** 6, 12 and 24 months

**Description:** Treatment failure: In case of treatment failure in either group, defined as persistent pain or a failed osteosynthesis, a salvage procedure with secondary osteosynthesis, including the possibility to use graft or a reverse shoulder arthroplasty (RSA), will be offered. Failed osteosynthesis and the most appropriate salvage procedure will be defined by the surgeon.

Cross-over to reverse shoulder arthroplasty or revision osteosynthesis is considered a failure of treatment regardless of group allocation. The patient will remain in the study. The reason for crossing over will be noted and reported.

**Measure:** Conversion to surgery after inclusion, or additional surgery

**Time Frame:** 24 months

**Description:** Serious adverse events, as defined by the WHO. Systemic reviews on terms and definitions for complications after surgical and non-surgical treatment have been conducted. Based on international consensus on the core event set for PHF, both surgical and non-surgical treatment, 8 event groups are defined. The following adverse event groups will be monitored: implant, osteochondral, shoulder instability, peripheral neurology, vascular, infection, device, superficial soft tissue, and deep soft tissue. In addition to this, we have chosen to monitor clinical symptoms such as persistent severe pain.

**Measure:** Adverse events.

**Time Frame:** 24 months

### Eligibility Module

**Eligibility Criteria:** Inclusion Criteria:

* Patients aged between 50 and 65 years with a displaced PHF assessed to be constructible by the treating surgeon after a low-energy trauma will be considered for eligibility.
* Patients should be cognitively capable of answering the follow-up questionnaires.

Exclusion Criteria:

* The patient does not understand written and spoken native language (Danish or Finnish/Swedish)
* Inability to give informed consent
* Fractures assessed to be unreconstructedly by the treating surgeon
* Isolated tuberosity fracture, fracture dislocations, open fractures, and fractures with involvement of the articular surface
* Less than 25% contact between head fragment and metaphysis/diaphysis measured at two perpendicular radiographs at two weeks.
* Pathological fractures or previous fractures in the same proximal humerus
* Concomitant fractures, which could influence the outcome
* Paralysis in upper extremity

**Maximum Age:** 65 Years

**Minimum Age:** 50 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** lihol@regionsjaelland.dk

**Name:** Line Løjbert Houkjær, M.D., ph.d.-student

**Phone:** 61711681

**Role:** CONTACT

**Contact 2:**

**Email:** sbror@regionsjaelland.dk

**Name:** Stig Brorson, Prof.

**Role:** CONTACT

#### Locations

**Location 1:**

**City:** Køge

**Contacts:**

***Contact 1:***

- **Email:** lihol@regionsjaelland.dk

- **Name:** Line Løjbert Houkjær, M.D., ph.d.-student

- **Phone:** 61711681

- **Role:** CONTACT

***Contact 2:***

- **Email:** sbror@regionsjaelland.dk

- **Name:** Stig Brorson

- **Role:** CONTACT

***Contact 3:***

- **Name:** Zaid Issa, M.D.

- **Role:** SUB_INVESTIGATOR

***Contact 4:***

- **Name:** Kenneth B Holtz, M.D.

- **Role:** SUB_INVESTIGATOR

**Country:** Denmark

**Facility:** Centre for Evidence-Based Orthopaedics, Zealand University Hospital

**State:** Region Zealand

**Zip:** 4600

**Location 2:**

**City:** Tampere

**Contacts:**

***Contact 1:***

- **Name:** Antti P Launonen, M.D.

- **Role:** CONTACT

***Contact 2:***

- **Name:** Bakir O. Sumrein, M.D.

- **Role:** SUB_INVESTIGATOR

**Country:** Finland

**Facility:** Tampere University Hospital

**Zip:** 33520

#### Overall Officials

**Official 1:**

**Affiliation:** Center for evidensbaseret ortopædkirurgi, Sjællands Universitets Hospital, Køge.

**Name:** Line Løjbert Houkjær, M.D.

**Role:** PRINCIPAL_INVESTIGATOR

### IPD Sharing Statement Module

**Description:** No individual participant data (IPD) available to other researchers.

**IPD Sharing:** NO

### References Module

#### References

**Citation:** Handoll HH, Elliott J, Thillemann TM, Aluko P, Brorson S. Interventions for treating proximal humeral fractures in adults. Cochrane Database Syst Rev. 2022 Jun 21;6(6):CD000434. doi: 10.1002/14651858.CD000434.pub5.

**PMID:** 35727196

**Citation:** Alispahic N, Brorson S, Bahrs C, Joeris A, Steinitz A, Audige L. Complications after surgical management of proximal humeral fractures: a systematic review of event terms and definitions. BMC Musculoskelet Disord. 2020 May 26;21(1):327. doi: 10.1186/s12891-020-03353-8.

**PMID:** 32456631

**Citation:** Brorson S, Alispahic N, Bahrs C, Joeris A, Steinitz A, Audige L. Complications after non-surgical management of proximal humeral fractures: a systematic review of terms and definitions. BMC Musculoskelet Disord. 2019 Feb 23;20(1):91. doi: 10.1186/s12891-019-2459-6.

**PMID:** 30797232

**Citation:** Audige L, Brorson S, Durchholz H, Lambert S, Moro F, Joeris A. Core set of unfavorable events of proximal humerus fracture treatment defined by an international Delphi consensus process. BMC Musculoskelet Disord. 2021 Nov 30;22(1):1002. doi: 10.1186/s12891-021-04887-1.

**PMID:** 34847888

#### See Also Links

**Label:** EMEA: Clinical Safety Data Management: Definitions and Standards for Expedited Reporting

**URL:** https://www.ema.europa.eu/en/documents/scientific-guideline/international-conference-harmonisation-technical-requirements-registration-pharmaceuticals-human-use-topic-e-2-clinical-safety-data-management-definitions-and-standards-expedited-reporting-step_en.pdf

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000014947

- Term: Wounds and Injuries

- ID: D000001134

- Term: Arm Injuries

- ID: D000070599

- Term: Shoulder Injuries

### Condition Browse Module - Browse Branches

- Abbrev: BC26

- Name: Wounds and Injuries

- Abbrev: All

- Name: All Conditions

### Condition Browse Module - Browse Leaves

- ID: M26370

- Name: Fractures, Bone

- Relevance: HIGH

- As Found: Fracture

- ID: M9869

- Name: Humeral Fractures

- Relevance: HIGH

- As Found: Humeral Fractures

- ID: M15592

- Name: Shoulder Fractures

- Relevance: HIGH

- As Found: Shoulder Fractures

- ID: M17685

- Name: Wounds and Injuries

- Relevance: LOW

- As Found: Unknown

- ID: M4444

- Name: Arm Injuries

- Relevance: LOW

- As Found: Unknown

- ID: M602

- Name: Shoulder Injuries

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000050723

- Term: Fractures, Bone

- ID: D000006810

- Term: Humeral Fractures

- ID: D000012784

- Term: Shoulder Fractures

### Misc Info Module

- Version Holder: 2024-05-31
