Scandinavian Humeral Diaphyseal Fracture Trial

NCT ID: NCT04574336

Last Updated: 2024-04-16

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

287 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-04-04

Study Completion Date

2031-07-31

Brief Summary

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This pragmatic multicenter randomized controlled trial (RCT) includes adult participants with an acute humeral shaft fracture to compare surgical fixation of humeral shaft fracture to non-surgical treatment with early identification and treatment of delayed union by a patient-reported outcome after 52 weeks. The trial population of 287 participants The trial population is divided in two age-groups due to the changes in DASH score by age. The definition of delayed union differs in the young and elderly population to consider dissimilarity in bone healing rates and the timepoint for crossover is therefor different between the groups. Participants will be randomized 1:1 between non-surgical treatment and surgical treatment. The primary outcome is the Disability of Arm, Shoulder and Hand (DASH) score at 52 weeks, and is assessor blinded. The secondary outcomes are DASH score earlier than 52 weeks, EQ-5D-5L, pain assessed by visual analogue score, Constant-Murley score including elbow range of motion and anchor-questions collected at all timepoints throughout the trial. All complications will be reported including; infection, nerve or vascular injury, surgical revisions (implant malpositioning, hardware failure, aseptic loosening and peri-implant fracture), major adverse cardiovascular events, other major adverse events and mortality. SHAFT will provide information on the effectiveness of two standard treatments for humeral shaft fractures, while taking the dilemmas within the population into account.

Detailed Description

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We will conduct a pragmatic multicenter, randomized, controlled, outcome assessor-blinded, clinical superiority trial. The objective is to compare surgical fixation of humeral shaft fracture to non-surgical treatment with early identification and treatment of delayed union by a patient-reported outcome after 52 weeks. .

Null-hypothesis:

The DASH score at 52 weeks after surgical treatment is not superior to non-surgical treatment with the option of early crossover surgery in patients with humeral shaft fractures

The trial population is divided in two age-groups due to the changes in DASH score by age. The definition of delayed union differs in the young and elderly population to consider dissimilarity in bone healing rates:

1. SHAFT-Y for the young with an age cut-off of 18 to 64 years. The early identification and treatment of delayed union is set to 6 to 12 weeks
2. SHAFT-E for the elder with an age cut-off +65 years. The early identification and treatment of delayed union is set to 12 to 26 weeks

Sites from Denmark, Sweden and Norway have been recruited and spans from academic level I to level III trauma centers

287 patients (n=163 for SHAFT-Y, n=124 for SHAFT-E) with a humeral shaft fracture will be equally randomized to surgical treatment or non-surgical treatment in each group.

Patients admitted to the emergency department in one of the trial sites and fulfil the eligibility criteria, will be invited to enroll into the trial. They will be given time to consider and be scheduled for a consultation with a trial worker within 10 days. If written consent is obtained at the consultation, randomization will occur immediately after.

Treatment will be performed within 14 days after injury

* Surgical treatment. The specific treatment is decided by the treating surgeon/department
* Non-surgical treatment with the option of early secondary surgery from 6-12 weeks for SHAFT-Y and 12-26 weeks for SHAFT-E

Patients can be offered to undergo early crossover fixation with a surgical procedure of the surgeon's choice, if one of these criteria are met:

* Unacceptable pain experienced by the patient
* Severe pain with gross instability of the fracture site assessed by:
* Unable to en bloc elevate the arm due to clear fracture instability
* Gentle manipulation of the fracture site. Gentle manipulation should respect the risk of callus breakage
* Severe problems tolerating the brace, e.g. discomfort, skin irritation, wounds, hygiene problems.

The patients that undergo early crossover surgery will have the reason for crossover thoroughly noted. We anticipate the surgical procedures will be similar to the ones previously mentioned with the possible addition of bone graft.

A computerized database software, Research Electronic Data Capture (REDCap) will be used to generate an irreversible random allocation sequence and perform block randomization with selected block sized of 2 and 4, which will be stratified on site and age (18-64 and +65). Patients will be assigned to the trial with an allocation of 1:1 to either surgical treatment or non-surgical treatment. The trial worker acquires the allocated treatment from the central coordinator with randomization rights to REDCap. The trial worker then initiates the treatment, either by scheduling the surgery date or applying the chosen non-surgical method.

The two groups (SHAFT-Y and SHAFT-E) require individual sample size calculations. Two standard deviations (SDs) were obtained from the data of the FISH trial(13) and were separated in age groups of 18-64 years and 65 years and above. By the distribution-based approach, one half a SD corresponds to the minimal important change (MIC). The calculations are powered to detect a MIC of 7 points in the young and 10 points in the elderly group in DASH, respectively. Two independent means sample size calculation were performed. For SHAFT-Y the following data were included: Mean difference= 7.0, SD= 14.91, α= 0.05 and power= 0.8. For SHAFT-E the following data were included: Mean difference= 10.0, SD= 18.59, α= 0.05 and power= 0.8. Based on the preceding assumptions and including an attrition of 15%, the total sample size is estimated to 163 patients for SHAFT-Y and 124 patients for SHAFT-E.

Primary analysis Descriptive statistics will be used to report demographic data. Demographic data and outcome measures will be tested visually and statistically (i.e. Shapiro Wilks test). Numeric variables will be summarized by means, standard deviations and 95% confidence intervals (95% CI). Median and interquartile ranges will be used when normal distribution is not met. Categorical variables will be summarized by frequency and proportion. For group comparison with numerical data, a student's t-test will be used if data is normally distributed, otherwise a non-parametric test will be used. For categorical data a Chi-square test will be used for group comparison. An intention-to-treat (ITT) analysis of the primary outcome will be conducted by univariable linear regression, including all patients that do not meet the withdrawal criteria and will be conducted to minimize bias within results. A sensitivity analysis will test the effects of non-adherence to protocol by conducting a per-protocol analysis and includes only patients who comply with the protocol. For missing data points in an outcome measure, a multiple imputation analysis using predictive covariates (age, sex, smoking, alcohol, UCLA activity, ASA grade)(50-52) will be conducted to deal with nonresponse bias. For comparison we will carry out a sensitivity analysis excluding all the missing values.

Data will be considered statistically significant if p-values \< 0.0471.

Secondary analysis In order to validate data a linear regression analysis will be computed with DASH score as the dependent variable and treatment modality as the independent variable. Additional regression analysis will be carried out between the early crossover group and the primary treatments. A multivariate regression analysis will be conducted to adjust for potential confounders. Variables adjusted for are: age, sex, smoking, alcohol, UCLA activity, ASA grade. Furthermore, we will analyze the longitudinal observations by applying a linear mixed effects regression model, including modality and time as well as a modality-time interaction as fixed effects and a random intercept for each patient. Data will be summarized as coefficients with 95% CIs and variance will be summarized as r-squares, adjusted r-squares, predicted r-squares, standard errors. Coefficients will be considered statistically significant if p-values \< 0.05.

Outcome timepoints Subjective and objective outcome measures will be obtained at following time points: pre-injury, baseline, 6 weeks, 12 weeks, 26 weeks, 52 weeks, 2 years and 5 years.

Conditions

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Fracture Humerus of Shaft

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Outcome Assessors

Study Groups

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Surgical Treatment

Primary surgery of humeral shaft fracture with surgeons choice of osteosynthesis method

Group Type EXPERIMENTAL

Surgical treatment

Intervention Type PROCEDURE

We anticipate that surgical treatment will include plate osteosynthesis (MIPO and ORIF), intramedullary nailing (antegrade and retrograde) and external fixation. Plate and nail types, screw configuration and surgical approaches will be decided by the surgeon. The procedure will be conducted or supervised by a senior consultant.

Non-surgical treatment

Treatment of humeral shaft fracture with sling and/or functional brace

Group Type ACTIVE_COMPARATOR

Non-surgical treatment

Intervention Type DEVICE

Non-surgical treatment will include sugar tong, splint, plaster splints, hanging casts, or functional bracing as the Sarmiento brace and will be worn until a surgeon removes it. If the surgeon deems it appropriate, participants will be offered to undergo early secondary surgery with a surgical procedure of their choice. The participants will be recorded and the reason will be noted. We anticipate the surgical procedures will be similar to the previous mentioned and perhaps with the addition of bone graft.

Interventions

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Surgical treatment

We anticipate that surgical treatment will include plate osteosynthesis (MIPO and ORIF), intramedullary nailing (antegrade and retrograde) and external fixation. Plate and nail types, screw configuration and surgical approaches will be decided by the surgeon. The procedure will be conducted or supervised by a senior consultant.

Intervention Type PROCEDURE

Non-surgical treatment

Non-surgical treatment will include sugar tong, splint, plaster splints, hanging casts, or functional bracing as the Sarmiento brace and will be worn until a surgeon removes it. If the surgeon deems it appropriate, participants will be offered to undergo early secondary surgery with a surgical procedure of their choice. The participants will be recorded and the reason will be noted. We anticipate the surgical procedures will be similar to the previous mentioned and perhaps with the addition of bone graft.

Intervention Type DEVICE

Eligibility Criteria

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Exclusion Criteria

1. Inability to give informed consent
2. Undisplaced shaft fracture (less than a cortex-wide displacement in all radiographic plane)
3. Vascular injury in ipsilateral arm
4. Polytrauma (defined as a trauma with one or more concurrent fractures to the upper extremities or other trauma absolute indications for surgical intervention)
5. Pathological fracture
6. Open fracture
7. BMI \> 40
8. Health conditions preventing either treatment
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Copenhagen University Hospital, Hvidovre

OTHER

Sponsor Role collaborator

Zealand University Hospital

OTHER

Sponsor Role collaborator

Oslo University Hospital

OTHER

Sponsor Role collaborator

Helse Stavanger HF

OTHER_GOV

Sponsor Role collaborator

Sahlgrenska University Hospital

OTHER

Sponsor Role collaborator

Uppsala University Hospital

OTHER

Sponsor Role collaborator

Odense University Hospital

OTHER

Sponsor Role collaborator

Hospital of Southern Jutland

OTHER

Sponsor Role collaborator

Slagelse Hospital

OTHER

Sponsor Role collaborator

Aalborg University Hospital

OTHER

Sponsor Role collaborator

University Hospital, Umeå

OTHER

Sponsor Role collaborator

Nordsjaellands Hospital

OTHER

Sponsor Role collaborator

Holbaek Sygehus

OTHER

Sponsor Role collaborator

Aarhus University Hospital

OTHER

Sponsor Role collaborator

Copenhagen University Hospital at Herlev

OTHER

Sponsor Role collaborator

University Hospital Bispebjerg and Frederiksberg

OTHER

Sponsor Role collaborator

Viborg Regional Hospital

OTHER

Sponsor Role collaborator

Karolinska University Hospital

OTHER

Sponsor Role collaborator

Danderyd Hospital

OTHER

Sponsor Role collaborator

Tampere University Hospital

OTHER

Sponsor Role collaborator

Helsinki University Central Hospital

OTHER

Sponsor Role collaborator

Kolding Sygehus

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Bjarke Viberg, MD, PhD

Role: STUDY_CHAIR

Hospital Lillebaelt

Locations

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Aabenraa Hospital

Aabenraa, , Denmark

Site Status RECRUITING

Aarhus Hospital

Aarhus, , Denmark

Site Status RECRUITING

Bispebjerg Hospital

Copenhagen, , Denmark

Site Status RECRUITING

Hvidovre Hospital

Copenhagen, , Denmark

Site Status RECRUITING

Esbjerg Hospital

Esbjerg, , Denmark

Site Status RECRUITING

Aalborg-Farsø Hospital

Farsø, , Denmark

Site Status RECRUITING

Herlev-Gentofte Hospital

Gentofte Municipality, , Denmark

Site Status RECRUITING

New North Zealand Hospital

Hillerød, , Denmark

Site Status RECRUITING

Holbæk Hospital

Holbæk, , Denmark

Site Status RECRUITING

Kolding Hospital

Kolding, , Denmark

Site Status RECRUITING

Zealand University

Køge, , Denmark

Site Status RECRUITING

Odense Hospital

Odense, , Denmark

Site Status RECRUITING

Slagelse Hospital

Slagelse, , Denmark

Site Status RECRUITING

Viborg Regional Hospital

Viborg, , Denmark

Site Status RECRUITING

Helsinki University Hospital

Helsinki, , Finland

Site Status RECRUITING

Tampere University Hospital

Tampere, , Finland

Site Status RECRUITING

Oslo University Hospital (Ullevål)

Oslo, , Norway

Site Status RECRUITING

Stanvanger University Hospital

Stavanger, , Norway

Site Status RECRUITING

Danderyd University Hospital

Stockholm, , Sweden

Site Status RECRUITING

Karolinska University Hospital

Stockholm, , Sweden

Site Status RECRUITING

Umeå University Hospital

Umeå, , Sweden

Site Status RECRUITING

Uppsala University Hospital

Uppsala, , Sweden

Site Status RECRUITING

Countries

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Denmark Finland Norway Sweden

Central Contacts

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Dennis Karimi, M.D

Role: CONTACT

+45 76363400

Bjarke Viberg, MD, PhD

Role: CONTACT

+45 76363067

Facility Contacts

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Jesper Schønnemann, M.D

Role: primary

Per Gundtoft, M.D.

Role: primary

Michael Kuhlmann, M.D

Role: primary

Søren Kring, M.D

Role: primary

Jens Knak

Role: primary

Esben Pedersen, M.D

Role: primary

Anne-Marie Nyholm

Role: primary

Peter Siesing-Mejer, M.D

Role: primary

Jacob Lagoni, M.D

Role: primary

Rasmus Bendtson, M.D.

Role: primary

Bamo Jalal, M.D

Role: primary

Joakim Jensen, M.D

Role: primary

Mads Vinding, M.D

Role: primary

Srdjan Zivanovic, M.D

Role: primary

Maire Ratasvuori, M.D., PhD.

Role: primary

Antti Launonen, M.D, PhD

Role: primary

Tore Fjalestad, M.D:

Role: primary

Aksel Paulsen, M.D.

Role: primary

Max Gordon, M.D.

Role: primary

Yan Li, M.D.

Role: primary

Jonas Sundkvist, M.D.

Role: primary

Olof Wolf, M.D.

Role: primary

References

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Gosler MW, Testroote M, Morrenhof JW, Janzing HM. Surgical versus non-surgical interventions for treating humeral shaft fractures in adults. Cochrane Database Syst Rev. 2012 Jan 18;1(1):CD008832. doi: 10.1002/14651858.CD008832.pub2.

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Ramo L, Sumrein BO, Lepola V, Lahdeoja T, Ranstam J, Paavola M, Jarvinen T, Taimela S; FISH Investigators. Effect of Surgery vs Functional Bracing on Functional Outcome Among Patients With Closed Displaced Humeral Shaft Fractures: The FISH Randomized Clinical Trial. JAMA. 2020 May 12;323(18):1792-1801. doi: 10.1001/jama.2020.3182.

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Reference Type BACKGROUND
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Hudak PL, Amadio PC, Bombardier C. Development of an upper extremity outcome measure: the DASH (disabilities of the arm, shoulder and hand) [corrected]. The Upper Extremity Collaborative Group (UECG). Am J Ind Med. 1996 Jun;29(6):602-8. doi: 10.1002/(SICI)1097-0274(199606)29:63.0.CO;2-L.

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Karimi D, Brorson S, Midtgaard KS, Fjalestad T, Paulsen A, Olerud P, Ekholm C, Wolf O, Viberg B; SHAFT Collaborators. Surgical versus non-surgical treatment of humeral SHAFT fractures compared by a patient-reported outcome: the Scandinavian Humeral diAphyseal Fracture Trial (SHAFT)-a study protocol for a pragmatic randomized controlled trial. Trials. 2022 Jun 2;23(1):453. doi: 10.1186/s13063-022-06317-6.

Reference Type DERIVED
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Other Identifiers

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SHAFT

Identifier Type: -

Identifier Source: org_study_id

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