Fracture Humerus of ShaftSHAFTNCT04574336
Scandinavian Humeral Diaphyseal Fracture Trial
A study testing Surgical treatment and Non-surgical treatment in people with Fracture Humerus of Shaft, run by Kolding Sygehus at 22 sites in 4 countries.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Fracture Humerus of Shaft
- What is being tested?
- Surgical treatment and Non-surgical treatment
- Type of treatment
- Medical device, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 287 participants
- Where
- 22 sitesin 4 countries
- Study dates
- 4 Apr 2022to 31 Jul 2031
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
None listed.
Who cannot join
- Inability to give informed consent
- Undisplaced shaft fracture (less than a cortex-wide displacement in all radiographic plane)
- Vascular injury in ipsilateral arm
- Polytrauma (defined as a trauma with one or more concurrent fractures to the upper extremities or other trauma absolute indications for surgical intervention)
- Pathological fracture
- Open fracture
- BMI > 40
- Health conditions preventing either treatment
Trial locations and contacts
22 sites in 4 countries. Contact the study team or a site near you to ask about taking part.
Bjarke Viberg, MD, PhD contact
22 sites in 4 countries
Denmark14 sites, 14 recruiting
- Recruiting
Aabenraa Hospital
Aabenraa
Jesper Schønnemann, M.D
- Recruiting
Aarhus Hospital
Aarhus
Per Gundtoft, M.D.
- Recruiting
Bispebjerg Hospital
Copenhagen
Michael Kuhlmann, M.D
- Recruiting
Hvidovre Hospital
Copenhagen
Søren Kring, M.D
- Recruiting
Esbjerg Hospital
Esbjerg
Jens Knak
- Recruiting
Aalborg-Farsø Hospital
Farsø
Esben Pedersen, M.D
- Recruiting
Herlev-Gentofte Hospital
Gentofte Municipality
Anne-Marie Nyholm
- Recruiting
New North Zealand Hospital
Hillerød
Peter Siesing-Mejer, M.D
- Recruiting
Holbæk Hospital
Holbæk
Jacob Lagoni, M.D
- Recruiting
Zealand University
Køge, 4600
Bamo Jalal, M.D
- Recruiting
Kolding Hospital
Kolding
Rasmus Bendtson, M.D.
- Recruiting
Odense Hospital
Odense
Joakim Jensen, M.D
- Recruiting
Slagelse Hospital
Slagelse
Mads Vinding, M.D
- Recruiting
Viborg Regional Hospital
Viborg, 8000
Srdjan Zivanovic, M.D
Sweden4 sites, 4 recruiting
- Recruiting
Danderyd University Hospital
Stockholm
Max Gordon, M.D.
- Recruiting
Karolinska University Hospital
Stockholm
Yan Li, M.D.
- Recruiting
Umeå University Hospital
Umeå
Jonas Sundkvist, M.D.
- Recruiting
Uppsala University Hospital
Uppsala
Olof Wolf, M.D.
Finland2 sites, 2 recruiting
- Recruiting
Helsinki University Hospital
Helsinki
Maire Ratasvuori, M.D., PhD.
- Recruiting
Tampere University Hospital
Tampere
Antti Launonen, M.D, PhD
Norway2 sites, 2 recruiting
- Recruiting
Oslo University Hospital (Ullevål)
Oslo
Tore Fjalestad, M.D:
- Recruiting
Stanvanger University Hospital
Stavanger
Aksel Paulsen, M.D.
About this study
Official title: Scandinavian Humeral diAphyseal Fracture Trial - A Pragmatic Randomized Controlled Trial
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.
Read the detailed description
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:
- 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
- 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
- Fracture Humerus of Shaft
- Being tested
- Surgical treatment, Non-surgical treatment
- Keywords
- Humeral shaft fracture, Diaphysis, Fracture fixation, Fracture Healing, Aged, Randomized Controlled Trial, Comparative study
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Surgical treatmentProcedure or surgery
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 treatmentDevice
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.
| Study group | Role | What they receive |
|---|---|---|
| Surgical Treatment | Experimental | Primary surgery of humeral shaft fracture with surgeons choice of osteosynthesis method Receives: Procedure: Surgical treatment |
| Non-surgical treatment | Active comparator | Treatment of humeral shaft fracture with sling and/or functional brace Receives: Device: Non-surgical treatment |
What is being measured
The primary outcome is the main question the study is designed to answer.
Disabilities of the Arm, Shoulder and Hand (DASH) score
A patient-reported outcome measure specific for physical function and symptoms of the upper limb (Disability of Arm, Shoulder and Hand-DASH). Scores range from 0 (no disability) to 100 (most severe disability)
Measured: 52 weeks
Secondary outcomes (7)
EuroQol-5 Domain (EQ-5D-5L)
EuroQol questionnaire for patient reported outcome concerning health related quality of life measure. The score includes five dimensions with 5 levels from 1 (indicating no problem) to 5 (indicating extreme problem). EQ-5D-5L describes 3125 potential health states. A score of 11111 indicates having no problems in any of the dimensions and a score of 55555 indicates having extreme problems in all of the dimensions.
Measured: Pre-Injury, 6 weeks, 12 weeks, 26 weeks, 52 weeks
Rate of complications
Complications after treatment will be recorded and include local complications, early general complication and mortality:
- Local complications: Infection (needing antibiotic treatment with or without debridement), nerve or vascular injury, surgical revision (due to implant malpositioning, hardware failure, aseptic loosening or peri-implant fracture) and tolerance problems with brace (discomfort resulting in non-compliance of wearing the brace
- Early general complications needing hospitalization within 12 weeks:
Major adverse cardiac events (MACE) including myocardial infarction, heart failure, thromboembolism, cardiomyopathy and cardiac arrythmias.
Other major adverse events including pneumonia, renal failure, electrolyte abnormality and deficiency anemia and other unforeseen reasons for hospitalization.
- Mortality
Measured: Up to 52 weeks
Visual Analogue Scale (VAS)
Visual analog scale is a pain score. Scores range from 0 (no pain) to 100 (worst pain).
Measured: Baseline, 6 weeks, 12 weeks, 26 weeks, 52 weeks
Anchor question
Anchor questions will include Clinical anchor questions (CAQ), Retrospective Global Transition questions (RGTQ) and Binary Repeat Treatment (BRT).
RGTQ and BRT will only be obtained at 52 weeks.
Measured: 6 weeks, 12 weeks, 26 weeks, 52 weeks
Constant-Murley score
Functional outcome with a 100-points scale. The higher the score, the higher the quality of the function.
Measured: 6 weeks, 12 weeks, 26 weeks, 52 weeks
Elbow range of motion
Range of motion is measured with a inclinometer.
Measured: 6 weeks, 12 weeks, 26 weeks, 52 weeks
Disabilities of the Arm, Shoulder and Hand (DASH) score
A patient-reported outcome measure specific for physical function and symptoms of the upper limb (Disability of Arm, Shoulder and Hand-DASH). Scores range from 0 (no disability) to 100 (most severe disability)
Measured: Pre-injury, 6 weeks, 12 weeks, 26 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Oct 2020
- Study start4 Apr 2022
- Primary completion31 Dec 2025 (estimated)
- Study completion31 Jul 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (20)Papers the sponsor has linked to this study.
- Other trials for Fracture Humerus of ShaftStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 287 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Kolding Sygehus
- Sponsor type
- University, hospital or other
- Collaborators
- Copenhagen University Hospital, Hvidovre, Zealand University Hospital, Oslo University Hospital, Helse Stavanger HF, Sahlgrenska University Hospital, Uppsala University Hospital, Odense University Hospital, Hospital of Southern Jutland, Slagelse Hospital, Aalborg University Hospital, University Hospital, Umeå, Nordsjaellands Hospital, Holbaek Sygehus, Aarhus University Hospital, Copenhagen University Hospital at Herlev, University Hospital Bispebjerg and Frederiksberg, Viborg Regional Hospital, Karolinska University Hospital, Danderyd Hospital, Tampere University Hospital, Helsinki University Central Hospital
- Responsible party
- Sponsor
- Investigators
- Bjarke Viberg, MD, PhD, Study chair, Hospital Lillebaelt
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04574336
- Sponsor's protocol ID
- SHAFT
- Acronym
- SHAFT
- Status last verified
- Jun 2023
- First submitted
- 28 Sep 2020
- Last updated
- 16 Apr 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Kim SH, Szabo RM, Marder RA. Epidemiology of humerus fractures in the United States: nationwide emergency department sample, 2008. Arthritis Care Res (Hoboken). 2012 Mar;64(3):407-14. doi: 10.1002/acr.21563.
PubMed 22162357Ekholm R, Adami J, Tidermark J, Hansson K, Tornkvist H, Ponzer S. Fractures of the shaft of the humerus. An epidemiological study of 401 fractures. J Bone Joint Surg Br. 2006 Nov;88(11):1469-73. doi: 10.1302/0301-620X.88B11.17634.
PubMed 17075092Gosler 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.
PubMed 22258990Harkin FE, Large RJ. Humeral shaft fractures: union outcomes in a large cohort. J Shoulder Elbow Surg. 2017 Nov;26(11):1881-1888. doi: 10.1016/j.jse.2017.07.001.
PubMed 29054684Matsunaga FT, Tamaoki MJ, Matsumoto MH, Netto NA, Faloppa F, Belloti JC. Minimally Invasive Osteosynthesis with a Bridge Plate Versus a Functional Brace for Humeral Shaft Fractures: A Randomized Controlled Trial. J Bone Joint Surg Am. 2017 Apr 5;99(7):583-592. doi: 10.2106/JBJS.16.00628.
PubMed 28375891van Middendorp JJ, Kazacsay F, Lichtenhahn P, Renner N, Babst R, Melcher G. Outcomes following operative and non-operative management of humeral midshaft fractures: a prospective, observational cohort study of 47 patients. Eur J Trauma Emerg Surg. 2011 Jun;37(3):287-96. doi: 10.1007/s00068-011-0099-0. Epub 2011 Apr 1.
PubMed 21837261Gottschalk MB, Carpenter W, Hiza E, Reisman W, Roberson J. Humeral Shaft Fracture Fixation: Incidence Rates and Complications as Reported by American Board of Orthopaedic Surgery Part II Candidates. J Bone Joint Surg Am. 2016 Sep 7;98(17):e71. doi: 10.2106/JBJS.15.01049.
PubMed 27605696Ramo 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.
PubMed 32396179Hosseini Khameneh SM, Abbasian M, Abrishamkarzadeh H, Bagheri S, Abdollahimajd F, Safdari F, Rahimi-Dehgolan S. Humeral shaft fracture: a randomized controlled trial of nonoperative versus operative management (plate fixation). Orthop Res Rev. 2019 Sep 23;11:141-147. doi: 10.2147/ORR.S212998. eCollection 2019.
PubMed 31576178Oliver WM, Carter TH, Graham C, White TO, Clement ND, Duckworth AD, Molyneux SG. A prospective randomised controlled trial of operative versus non-operative management of fractures of the humeral diaphysis: the HUmeral Shaft Fracture FIXation (HU-FIX) Study protocol. Trials. 2019 Aug 5;20(1):475. doi: 10.1186/s13063-019-3576-0.
PubMed 31383027Kurup H, Hossain M, Andrew JG. Dynamic compression plating versus locked intramedullary nailing for humeral shaft fractures in adults. Cochrane Database Syst Rev. 2011 Jun 15;2011(6):CD005959. doi: 10.1002/14651858.CD005959.pub2.
PubMed 21678350Driesman AS, Fisher N, Karia R, Konda S, Egol KA. Fracture Site Mobility at 6 Weeks After Humeral Shaft Fracture Predicts Nonunion Without Surgery. J Orthop Trauma. 2017 Dec;31(12):657-662. doi: 10.1097/BOT.0000000000000960.
PubMed 28708781Chan AW, Tetzlaff JM, Gotzsche PC, Altman DG, Mann H, Berlin JA, Dickersin K, Hrobjartsson A, Schulz KF, Parulekar WR, Krleza-Jeric K, Laupacis A, Moher D. SPIRIT 2013 explanation and elaboration: guidance for protocols of clinical trials. BMJ. 2013 Jan 8;346:e7586. doi: 10.1136/bmj.e7586.
PubMed 23303884Loudon K, Treweek S, Sullivan F, Donnan P, Thorpe KE, Zwarenstein M. The PRECIS-2 tool: designing trials that are fit for purpose. BMJ. 2015 May 8;350:h2147. doi: 10.1136/bmj.h2147. No abstract available.
PubMed 25956159Harris PA, Taylor R, Thielke R, Payne J, Gonzalez N, Conde JG. Research electronic data capture (REDCap)--a metadata-driven methodology and workflow process for providing translational research informatics support. J Biomed Inform. 2009 Apr;42(2):377-81. doi: 10.1016/j.jbi.2008.08.010. Epub 2008 Sep 30.
PubMed 18929686
Study at a glance
From the registry record, last updated by the sponsor on 16 Apr 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Scandinavian Humeral diAphyseal Fracture Trial - A Pragmatic Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT04574336
- Acronym / sponsor ID
- SHAFT / SHAFT
- Conditions
- Fracture Humerus of Shaft
- Keywords
- Humeral shaft fracture, Diaphysis, Fracture fixation, Fracture Healing, Aged, Randomized Controlled Trial, Comparative study
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 287 participants (estimated)
- Lead sponsor
- Kolding SygehusUniversity, hospital or other
- Collaborators
- Copenhagen University Hospital, Hvidovre, Zealand University Hospital, Oslo University Hospital, Helse Stavanger HF, Sahlgrenska University Hospital, Uppsala University Hospital, Odense University Hospital, Hospital of Southern Jutland, Slagelse Hospital, Aalborg University Hospital, University Hospital, Umeå, Nordsjaellands Hospital, Holbaek Sygehus, Aarhus University Hospital, Copenhagen University Hospital at Herlev, University Hospital Bispebjerg and Frederiksberg, Viborg Regional Hospital, Karolinska University Hospital, Danderyd Hospital, Tampere University Hospital, Helsinki University Central Hospital
- Study start
- 4 Apr 2022 (actual)
- Primary completion
- 31 Dec 2025 (estimated)
- Study completion
- 31 Jul 2031 (estimated)
- First posted
- 5 Oct 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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:
- 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
- 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Surgical Treatment | Experimental | Procedure: Surgical treatmentPrimary surgery of humeral shaft fracture with surgeons choice of osteosynthesis method |
| Non-surgical treatment | Active comparator | Device: Non-surgical treatmentTreatment of humeral shaft fracture with sling and/or functional brace |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (0 listed)
Key exclusion criteria (8 listed)
- Inability to give informed consent
- Undisplaced shaft fracture (less than a cortex-wide displacement in all radiographic plane)
- Vascular injury in ipsilateral arm
- Polytrauma (defined as a trauma with one or more concurrent fractures to the upper extremities or other trauma absolute indications for surgical intervention)
- Pathological fracture
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Surgical treatmentWe 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. | Procedure or surgery | Surgical Treatment |
| Non-surgical treatmentNon-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. | Device | Non-surgical treatment |
Primary outcome
Disabilities of the Arm, Shoulder and Hand (DASH) score
Time frame: 52 weeks
A patient-reported outcome measure specific for physical function and symptoms of the upper limb (Disability of Arm, Shoulder and Hand-DASH). Scores range from 0 (no disability) to 100 (most severe disability)
7 secondary outcomes
EuroQol-5 Domain (EQ-5D-5L)
Time frame: Pre-Injury, 6 weeks, 12 weeks, 26 weeks, 52 weeks
Rate of complications
Time frame: Up to 52 weeks
Visual Analogue Scale (VAS)
Time frame: Baseline, 6 weeks, 12 weeks, 26 weeks, 52 weeks
Anchor question
Time frame: 6 weeks, 12 weeks, 26 weeks, 52 weeks
Constant-Murley score
Time frame: 6 weeks, 12 weeks, 26 weeks, 52 weeks
Elbow range of motion
Time frame: 6 weeks, 12 weeks, 26 weeks, 52 weeks
Disabilities of the Arm, Shoulder and Hand (DASH) score
Time frame: Pre-injury, 6 weeks, 12 weeks, 26 weeks
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Apr 2024.
- Background: PubMed 22162357Kim SH, Szabo RM, Marder RA. Epidemiology of humerus fractures in the United States: nationwide emergency department sample, 2008. Arthritis Care Res (Hoboken). 2012 Mar;64(3):407-14. doi: 10.1002/acr.21563.
- Background: PubMed 17075092Ekholm R, Adami J, Tidermark J, Hansson K, Tornkvist H, Ponzer S. Fractures of the shaft of the humerus. An epidemiological study of 401 fractures. J Bone Joint Surg Br. 2006 Nov;88(11):1469-73. doi: 10.1302/0301-620X.88B11.17634.
- Background: PubMed 22258990Gosler 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.
- Background: PubMed 29054684Harkin FE, Large RJ. Humeral shaft fractures: union outcomes in a large cohort. J Shoulder Elbow Surg. 2017 Nov;26(11):1881-1888. doi: 10.1016/j.jse.2017.07.001.
- Background: PubMed 28375891Matsunaga FT, Tamaoki MJ, Matsumoto MH, Netto NA, Faloppa F, Belloti JC. Minimally Invasive Osteosynthesis with a Bridge Plate Versus a Functional Brace for Humeral Shaft Fractures: A Randomized Controlled Trial. J Bone Joint Surg Am. 2017 Apr 5;99(7):583-592. doi: 10.2106/JBJS.16.00628.
- Background: PubMed 21837261van Middendorp JJ, Kazacsay F, Lichtenhahn P, Renner N, Babst R, Melcher G. Outcomes following operative and non-operative management of humeral midshaft fractures: a prospective, observational cohort study of 47 patients. Eur J Trauma Emerg Surg. 2011 Jun;37(3):287-96. doi: 10.1007/s00068-011-0099-0. Epub 2011 Apr 1.
- Background: PubMed 27605696Gottschalk MB, Carpenter W, Hiza E, Reisman W, Roberson J. Humeral Shaft Fracture Fixation: Incidence Rates and Complications as Reported by American Board of Orthopaedic Surgery Part II Candidates. J Bone Joint Surg Am. 2016 Sep 7;98(17):e71. doi: 10.2106/JBJS.15.01049.
- Background: PubMed 32396179Ramo 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.
- Background: PubMed 31576178Hosseini Khameneh SM, Abbasian M, Abrishamkarzadeh H, Bagheri S, Abdollahimajd F, Safdari F, Rahimi-Dehgolan S. Humeral shaft fracture: a randomized controlled trial of nonoperative versus operative management (plate fixation). Orthop Res Rev. 2019 Sep 23;11:141-147. doi: 10.2147/ORR.S212998. eCollection 2019.
- Background: PubMed 31383027Oliver WM, Carter TH, Graham C, White TO, Clement ND, Duckworth AD, Molyneux SG. A prospective randomised controlled trial of operative versus non-operative management of fractures of the humeral diaphysis: the HUmeral Shaft Fracture FIXation (HU-FIX) Study protocol. Trials. 2019 Aug 5;20(1):475. doi: 10.1186/s13063-019-3576-0.
- Background: PubMed 21678350Kurup H, Hossain M, Andrew JG. Dynamic compression plating versus locked intramedullary nailing for humeral shaft fractures in adults. Cochrane Database Syst Rev. 2011 Jun 15;2011(6):CD005959. doi: 10.1002/14651858.CD005959.pub2.
- Background: PubMed 28708781Driesman AS, Fisher N, Karia R, Konda S, Egol KA. Fracture Site Mobility at 6 Weeks After Humeral Shaft Fracture Predicts Nonunion Without Surgery. J Orthop Trauma. 2017 Dec;31(12):657-662. doi: 10.1097/BOT.0000000000000960.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Bjarke Viberg, MD, PhD contact
Bjarke Viberg, MD, PhD study chair
Hospital Lillebaelt
22 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Surgical treatment and Non-surgical treatment in people with Fracture Humerus of Shaft, run by Kolding Sygehus at 22 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 0 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 16 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 22 sites in Denmark, Sweden, Finland, Norway. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Dennis Karimi, M.D (+45 76363400, denniskarimi@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Disabilities of the Arm, Shoulder and Hand (DASH) score (time frame: 52 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04574336, which also lists 20 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Apr 2024.