Patient selection

The eligible study population will comprise all consecutive patients aged 15 to 35 years with closed growth plate (physis) who have been referred for DTTO surgery at Pihlajalinna Koskisairaala Hospital, Tampere, Finland. The upper age limit was chosen to minimize the effect of patellofemoral osteoarthritis. As the DTTO procedure can only be planned for skeletally mature patients, the closure of the physis will be evaluated with magnetic resonance imaging (MRI) and plain radiographs. The Greulich and Pyle method will be used to define skeletal age if needed [7].

Only those patients with isolated DTTO or DTTO combined with medial patellofemoral ligament reconstruction will be included in the study. At the initial out-patient ward the treating physician will give the information about the study and ask for written informed consent.

The following criteria will be used for patient selection throughout the study.

1. ❖ Inclusion criteria
   • Symptomatic patella alta with recurrent dislocation or subluxation. Long-lasting anterior knee pain not responding to rehabilitation.
2. ❖ Exclusion criteria
   1. ➢ Radiographic:
      • Open growth plates
      • Iwano [8] grade III and IV changes in patellofemoral joint
      • Caton-Deschamps <1.2 in MRI
      • PTI >30% in MRI
      • High grade trochlear dysplasia
   2. ➢ General:
   • Refuses to participate in the study
   • Aged less than 15 or more than 35 years
   • Severe neurological, pulmonal or cardiovascular comorbidities that are contraindications for surgery
   • Lack of adequate co-operation
   • Does not adequately understand written and spoken instructions in the local language

Those patients who decline to take part in the trial will be asked to join a follow-up cohort as a background population. The patients in this follow-up cohort will be treated “as normal” without allocation, but the follow-up questionnaires will be the same as those given to the randomly assigned population. The patients in the follow-up cohort will also be asked to provide informed written consent.

Randomisation

Patients will be randomised using a pre-trial random number matrix in block allocation fashion in varying block. We have two stratification factors. First is age (under 20 and 20–35 years) since age has been shown to associate with the main outcome measure. Another stratification factor will be history of the patellar dislocation i.e. group 1- history with at least 1 documented patellar dislocation and group 2-history with no documented patellar dislocation.

Randomisation will be performed using an online randomisation platform (Redcap). After informed written consent has been received and the intervention in the OR performed, the patients will be randomly allocated for rehabilitation. The physician responsible for the intervention or treatment will not participate in the collection of patient outcomes during the follow-up. Patients are encouraged not to reveal the group to the assessor, so assessor will be blinded. The Patients research data will be concealed to Redcap program until the blinded analysis and two versions of discussions has been agreed. After which the group will be revealed. The research coordinator will monitor the study flow. An independent monitoring committee, which was established during our previous randomised controlled trial, will monitor the study.

Surgical treatment

Operative treatment will be performed by trained and experienced knee surgeons. The surgeons’ skills and number of procedures will be reported according to the criteria given by the Consort Group [9].

The aim of the surgical treatment is to normalise the biomechanics of the patellofemoral joint. The operation will start with an arthroscopic examination to verify patella alta position. The high-positioned patella in relation to the trochlea will be documented and an approximation made of the required distalisation for adequate cartilage contact between the patella and the trochlea. Thereafter, a 5–7 cm mid-line incision will be made at the tibial tubercle. The gracilis graft will be harvested from the same incision if needed for medial patellofemoral ligament reconstruction. The lateral aspect of the tibial tubercle will be exposed. The proximal distalisation cut will be made in AP direction at 70º angle at a minimum of 6–7 cm distally from the tibial tubercle. The distal AP cut will be done according to preoperative measurements taken from imagining data and the arthroscopic findings of the patient. The bone block will be removed to allow distalisation of the tubercle. Furthermore, the tubercle will be mobilised with chisels to allow the distalisation of the tubercle. The distalisation is at least 5 mm, usually even more. The osteotomy will be fixed with two 4.5 mm AO screws. The appropriate localisation of the fixation and patella will be confirmed with fluoroscopy.

Rehabilitation

Patients will be randomised in two rehabilitation groups. Patients in both groups will be guided by in-ward physiotherapists and will be given written physiotherapy guidelines for both instructed physiotherapy and self-guided exercises. After discharge from the hospital, patients will be referred to physiotherapy for further guidance. Both groups will start preliminary exercises from the first postoperative day to reduce oedema in the operated lower limb. For the detailed rehabilitation guidelines, please see Table 2.

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Table 2. The rehabilitation guidelines.

https://doi.org/10.1371/journal.pone.0304075.t002

Follow-up

Postoperative physiotherapy control visits will take place at 6, 12, 24 and 52 weeks after the procedure. The physiotherapy control visits will be managed by a senior physiotherapist who will be blinded to the allocation group. During the visits, knee ROM and isometric flexion/extension strength will be measured. The isometric extension and flexion strength will be measured with an SBS-KW-300SLIM scale. In addition, the PROMs (KOOS and BPI) will be collected during the research related control visits by the senior physiotherapist at previously defined time points (Table 2).

Postoperative physiotherapy sessions will be provided by physiotherapists who will not otherwise be involved in the study. Physiotherapy control visits and rehabilitation guidance sessions with the treating physiotherapist will take place at 1, 4, 6, 8, 12 and 24 weeks. The physiotherapy protocol will last for 24 weeks. Protocols 1 and 2 are presented in the supplementary material.

Healing of the osteotomy site will be evaluated with plain radiograph examination at 6 and 12 weeks after the procedure. The radiographs will be evaluated by an experienced radiologist and the operating surgeons. Physician visits will be at 6 and 12 weeks. Knee scores and isometric flexion/extension strength will be assessed preoperatively and at 12 and 52 weeks postoperatively.

Power analysis

We defined 10 degrees [10] in knee ROM in the primary end-point as a clinically relevant difference we would not like miss. We estimated a common standard population deviation of 20 degrees for knee ROM in both groups. Based on unadjusted t-test (TrialSize package in R), we need 63 patients per group to have a power of 80% with 5% type I error level. With this age group, the estimate of loss to follow-up rate will be set to 5% and will result in a total of 132 patients participating in the trial.

Statistical analysis

Study analysis will be done using mixed linear model allowing for repeated measures in longitudinal setting. All continuous variables will be analyses in this fashion. Each outcome variable will be the dependent variable and patient the random factor. Study group and time point will be included as fixed factor. Stratification variables are included as covariates in the analysis. If baseline value for the dependent variable (i.e. ROM) is available, it will be included also as a covariate. Treatment effects at each time point are the estimated marginal means for time point and study group interaction term. Satterthwaite method is used to estimate degrees in freedom in these analyses. No imputation is needed as liner mixed model is used and a full data set will be used in the analyses. Logistic regression is used to analyse binary outcome. Adjusted risk difference at each time point will be reported for complications and reoperations. All analyses will done with RStudio with suitable packages (i.e. lmer and emmean).

Data management plan

Electronic portfolios provided by the Redcap application at Tampere university hospital’s server will be used to collect patient research data. Patients will be de-identified: each patient will be assigned a unique trial identification number (TIN), which is then matched with the patient’s personal identification number. The identification of each patient will only be possible after retrieving the matching key, which will be stored in a locked locker in the research nurse’s office at Pihlajalinna Koskisairaala Hospital. Access to patient research data will not be given to parties outside the trial. Throughout the trial, the research data will only be handled with a TIN.

Data will be saved electronically by patients and research personnel to Tampere University Hospital’s secure research server–Redcap (via tablets and laptops), which has been security cleared by the hospital district. The research data saved to the server will contain only pseudonymous TINs with a set of numbers acquired from the questionnaires; that is, each question is answered with a number. This will ensure the anonymity of each individual patient, and that the identity of the patient will remain secret, even if server data are revealed to third parties.

Each researcher participating in the trial will gain access to the data at the end of the trial for further analyses. All variables in the data set will be described, and suitable metadata standards will be used, when available.

The copyright of the trial research data will be owned and created by the participating research parties. The data will be shared among all participating researchers who will receive access to the data after the trial is completed. Due to confidentiality and legal agreements, public data sharing will be restricted because we only have permission to hold the data in the specific research server, not to transfer data. Under certain circumstances, for example, when a new member joins the collaboration, we will grant access to the data.

Members of study group have access to the password-protected study data for analysis. All research team members are bound by professional secrecy with respect to identifiable patient information. The results of the study will be published in a form that does not identify those individuals who participated in the study.

Interim analysis

The external trial board will execute the interim analysis after half of the patients have been recruited. The analysis will focus on the number of adverse events and the trial board, based on the results of the analysis, will give a recommendation as to whether the trial should continue. If complications rate in accelerated rehabilitation group is remarkably increased in that phase, the study is discarded. Adverse events and serious adverse events will be reported according to the recommendations given by the Consort Group. They will be reported as complications in the final analysis.

Adverse event is defined as follows:

1. ➢ Superficial infection
2. ➢ Persisting pain, complex regional pain syndrome or other reasons that can be cured on an ambulatory basis.

Serious adverse event is defined as follows:

1. ➢ Deep infection: Any infection with known bacterial source that calls for re-operation
2. ➢ Implant failure leading to displacement of the osteotomy
3. ➢ Non-union at 12 weeks control visit

Trial schedule

Approval for the study was sought in the autumn of 2022. Patient recruitment will start in the spring of 2024. The study will document short-term recovery and the planned follow-up will be 1 year. The number of operations will be collected until the spring of 2025. Follow-up control visits will take place until the spring of 2026.

After the 1-year follow-up, the results of the trial will be disseminated in a major peer-reviewed orthopaedic publication.