Total Knee ArthroplastySAFE-TNCT07067060
Risk of Serious Adverse Events Following Unsupervised vs Supervised Rehabilitation After Knee Arthroplasty
An observational study of Total Knee Arthroplasty and Knee Arthroplasty, run by Copenhagen University Hospital, Hvidovre.
Trial summary
SUMMARY Background: After knee arthroplasty (KA), rehabilitation is widely recommended, yet its clinical effectiveness-especially the need for supervision-has been challenged. While some argue that supervised rehabilitation may prevent serious adverse events (SAEs), previous trials show no superiority of… Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Total Knee Arthroplasty, Knee Arthroplasty, Unicompartmental Knee Arthroplasty
- How many people
- 40,000 participants
- Where
- No sites listed yet
- Study dates
- 1 Jan 2026to 31 Dec 2027
- How long will I take part?
- 2 Years
- Phase
- Observational
- 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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: Each year, approximately 14,000-15,000 patients undergo knee arthroplasty in Denmark. These procedures take place in both public and private hospitals, all following fast-track surgery protocols with standardized pre-, peri-, and post-operative routines. Hospitals are legally required to report specific hospital-related data to the National Patient Register and the Danish Knee Arthroplasty Register, ensuring high data completeness.
Who may be able to join
- Adults undergoing primary total or unicompartmental knee arthroplasty (KA) for osteoarthritis in Denmark
Who cannot join
- None
About this study
Official title: Risk of Serious Adverse Events Following Unsupervised vs Supervised Rehabilitation After Knee Arthroplasty: Protocol For An Emulated Noninferiority Trial (SAFE-T)
SUMMARY
Background:
Read more
After knee arthroplasty (KA), rehabilitation is widely recommended, yet its clinical effectiveness-especially the need for supervision-has been challenged. While some argue that supervised rehabilitation may prevent serious adverse events (SAEs), previous trials show no superiority of rehabilitation, supervised or not, over no rehabilitation in terms of function. However, these trials were underpowered for safety outcomes. A large-scale evaluation is needed to determine if supervision impacts SAE risk, thereby informing rational use of health care resources.
Rationale for the proposed study. A conventional randomized trial to assess the safety of supervised versus unsupervised rehabilitation after KA would require an ethically and logistically infeasible sample size. By emulating such a trial using routinely collected registry data, the investigators can estimate the causal effect of supervision on the risk of serious adverse events-while accounting for confounding and preserving real-world relevance.
Actionable objective and hypothesis: To test whether unsupervised rehabilitation after knee arthroplasty increases the risk of serious adverse events over a 2-year period compared with supervised rehabilitation. The investigators hypothesize that unsupervised rehabilitation is non-inferior, defined as a hazard ratio for SAE risk below 1.4.
Design: Target trial emulation (TTE) using nationwide registry data to replicate the design and intent of a pragmatic randomized trial.
Setting: Danish hospitals and municipalities. Patients: Adults undergoing primary total or unicompartmental knee arthroplasty for osteoarthritis, identified from Danish registries. The target trial assumes consecutive recruitment at hospital discharge to mirror real-world referral practices.
Interventions: Referral to unsupervised home-based exercise or supervised municipal physiotherapy, defined by referral to rehabilitation pathways initiated at hospital discharge.
Methods: Primary outcome is serious adverse events; secondary is number of hospital contacts. Propensity score-based weighting will adjust for confounding using patient and administrative covariates (e.g. age, BMI, comorbidities, surgery year), enabling causal inference from observational data.
Results: Findings will inform clinical practice by estimating the comparative safety of unsupervised versus supervised rehabilitation after knee arthroplasty, based on real-world data from over 40,000 patients.
Limitations: As with all non-randomized studies, residual confounding is possible. Despite adjustment strategies, causal interpretations should be made with caution due to reliance on observational data.
Conclusion: While TTE can provide valuable insight, the causal inferences made with TTE should be interpreted with caution, when not supported with an RCT.
Funding: Section for Biostatistics and Evidence-Based Research, the Parker Institute, Bispebjerg and Frederiksberg Hospital is supported by a core grant from the Oak Foundation (OFIL-24-074).
External funding: in process. Registration: TBD (registration on ClinicalTrials.Gov)
- Keywords
- emulated target trial, total knee replacement, arthroplasty, serious adverse events, supervised rehabilitation, unsupervised rehabilitation
What is being measured
The primary outcome is the main question the study is designed to answer.
Serious adverse events (SAE)
The term "serious adverse events" (SAE) is defined by the ICH framework as any untoward medical occurrence that, at any dose, results in: 1) death, 2) life-threatening conditions, 3) inpatient hospitalization or prolonged existing hospitalization, 4) persistent or significant disability/incapacity, or 5) congenital anomalies/birth defects.
Measured: 2 years
Serious adverse events (SAE)
The term "serious adverse events" (SAE) is defined by the ICH framework as any untoward medical occurrence that, at any dose, results in: 1) death, 2) life-threatening conditions, 3) inpatient hospitalization or prolonged existing hospitalization, 4) persistent or significant disability/incapacity, or 5) congenital anomalies/birth defects
Measured: 2 years
Secondary outcomes (1)
Hospital contact
Number of hospital contact
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Jul 2025
- Study start1 Jan 2026 (estimated)
- Primary completion31 Dec 2026 (estimated)
- Study completion31 Dec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Total Knee ArthroplastyStudies 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
- Observational
- Observational model
- Cohort
- Time perspective
- Other
- Enrolment
- 40,000 participants (estimated)
- Target duration
- 2 Years
Sponsor and investigators
- Lead sponsor
- Copenhagen University Hospital, Hvidovre
- Sponsor type
- University, hospital or other
- Collaborators
- University of Southern Denmark, University Hospital Bispebjerg and Frederiksberg
- Responsible party
- Principal investigator, Troels Mark-Christensen, Copenhagen University Hospital, Hvidovre
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07067060
- Sponsor's protocol ID
- 10062025
- Acronym
- SAFE-T
- Status last verified
- Jul 2025
- First submitted
- 4 Jul 2025
- Last updated
- 31 Jul 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: The investigators might share individual participant data (IPD) in anonymized form where possible, in accordance with ethical approvals and data protection regulations. Access might be granted upon reasonable request and under a data-sharing agreement to ensure participant confidentiality and legal compliance.
Study at a glance
From the registry record, last updated by the sponsor on 31 Jul 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Risk of Serious Adverse Events Following Unsupervised vs Supervised Rehabilitation After Knee Arthroplasty: Protocol For An Emulated Noninferiority Trial (SAFE-T)
- ClinicalTrials.gov ID
- NCT07067060
- Acronym / sponsor ID
- SAFE-T / 10062025
- Keywords
- emulated target trial, total knee replacement, arthroplasty, serious adverse events, supervised rehabilitation, unsupervised rehabilitation
- Study type
- Observational
- Recruitment status
- Not yet recruiting
- Enrolment
- 40,000 participants (estimated)
- Lead sponsor
- Copenhagen University Hospital, HvidovreUniversity, hospital or other
- Collaborators
- University of Southern Denmark, University Hospital Bispebjerg and Frederiksberg
- Study start
- 1 Jan 2026 (estimated)
- Primary completion
- 31 Dec 2026 (estimated)
- Study completion
- 31 Dec 2027 (estimated)
- First posted
- 15 Jul 2025 (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.
SUMMARY
Background:
After knee arthroplasty (KA), rehabilitation is widely recommended, yet its clinical effectiveness-especially the need for supervision-has been challenged. While some argue that supervised rehabilitation may prevent serious adverse events (SAEs), previous trials show no superiority of rehabilitation, supervised or not, over no rehabilitation in terms of function. However, these trials were underpowered for safety outcomes. A large-scale evaluation is needed to determine if supervision impacts SAE risk, thereby informing rational use of health care resources.
Rationale for the proposed study. A conventional randomized trial to assess the safety of supervised versus unsupervised rehabilitation after KA would require an ethically and logistically infeasible sample size. By emulating such a trial using routinely collected registry data, the investigators can estimate the causal effect of supervision on the risk of serious adverse events-while accounting for confounding and preserving real-world relevance.
Actionable objective and hypothesis: To test whether unsupervised rehabilitation after knee arthroplasty increases the risk of serious adverse events over a 2-year period compared with supervised rehabilitation. The investigators hypothesize that unsupervised rehabilitation is non-inferior, defined as a hazard ratio for SAE risk below 1.4.
Design: Target trial emulation (TTE) using nationwide registry data to replicate the design and intent of a pragmatic randomized trial.
Setting: Danish hospitals and municipalities. Patients: Adults undergoing primary total or unicompartmental knee arthroplasty for osteoarthritis, identified from Danish registries. The target trial assumes consecutive recruitment at hospital discharge to mirror real-world referral practices.
Interventions: Referral to unsupervised home-based exercise or supervised municipal physiotherapy, defined by referral to rehabilitation pathways initiated at hospital discharge.
Methods: Primary outcome is serious adverse events; secondary is number of hospital contacts. Propensity score-based weighting will adjust for confounding using patient and administrative covariates (e.g. age, BMI, comorbidities, surgery year), enabling causal inference from observational data.
Results: Findings will inform clinical practice by estimating the comparative safety of unsupervised versus supervised rehabilitation after knee arthroplasty, based on real-world data from over 40,000 patients.
Limitations: As with all non-randomized studies, residual confounding is possible. Despite adjustment strategies, causal interpretations should be made with caution due to reliance on observational data.
Conclusion: While TTE can provide valuable insight, the causal inferences made with TTE should be interpreted with caution, when not supported with an RCT.
Funding: Section for Biostatistics and Evidence-Based Research, the Parker Institute, Bispebjerg and Frederiksberg Hospital is supported by a core grant from the Oak Foundation (OFIL-24-074).
External funding: in process. Registration: TBD (registration on ClinicalTrials.Gov)
Study design
- Observational model
- Cohort
- Time perspective
- Other
- Target follow-up
- 2 Years
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Each year, approximately 14,000-15,000 patients undergo knee arthroplasty in Denmark. These procedures take place in both public and private hospitals, all following fast-track surgery protocols with standardized pre-, peri-, and post-operative routines. Hospitals are legally required to report specific hospital-related data to the National Patient Register and the Danish Knee Arthroplasty Register, ensuring high data completeness.
Key inclusion criteria (1 listed)
- Adults undergoing primary total or unicompartmental knee arthroplasty (KA) for osteoarthritis in Denmark
Key exclusion criteria (1 listed)
- None
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Serious adverse events (SAE)
Time frame: 2 years
The term "serious adverse events" (SAE) is defined by the ICH framework as any untoward medical occurrence that, at any dose, results in: 1) death, 2) life-threatening conditions, 3) inpatient hospitalization or prolonged existing hospitalization, 4) persistent or significant disability/incapacity, or 5) congenital anomalies/birth defects.
Serious adverse events (SAE)
Time frame: 2 years
The term "serious adverse events" (SAE) is defined by the ICH framework as any untoward medical occurrence that, at any dose, results in: 1) death, 2) life-threatening conditions, 3) inpatient hospitalization or prolonged existing hospitalization, 4) persistent or significant disability/incapacity, or 5) congenital anomalies/birth defects
1 secondary outcome
Hospital contact
Time frame: 2 years
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 31 Jul 2025.
- Individual participant dataSharing planned: Undecided. The investigators might share individual participant data (IPD) in anonymized form where possible, in accordance with ethical approvals and data protection regulations. Access might be granted upon reasonable request and under a data-sharing agreement to ensure participant confidentiality and legal compliance.
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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.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
An observational study of Total Knee Arthroplasty and Knee Arthroplasty, run by Copenhagen University Hospital, Hvidovre.
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 1 inclusion and 1 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: opening soon, as of the sponsor's last update on 31 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.
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?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Serious adverse events (SAE) (time frame: 2 years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 31 Jul 2025.