PATH2: Platelet rich plasma in Achilles tendon healing

ISRCTN ISRCTN54992179
DOI https://doi.org/10.1186/ISRCTN54992179
IRAS number 146684
ClinicalTrials.gov number NCT02302664
Secondary identifying numbers 17850, IRAS 146684
Submission date
08/01/2015
Registration date
12/01/2015
Last edited
11/06/2025
Recruitment status
No longer recruiting
Overall study status
Completed
Condition category
Musculoskeletal Diseases
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data

Plain English summary of protocol

Background and study aims
Achilles tendon rupture (ATR) is when a person tears the tendon (the Achilles tendon) connecting the calf muscle and heal bone. It is the most common tendon injury and lead to months of incapacity. With an average work absence of 63-108 days there are significant costs to society and to the NHS. Platelet rich plasma (PRP) may improve recovery and return to normal activities earlier, and reduce the NHS and societal impact. This study investigates how good PRP is at treating ATR using disease-specific and patient important outcomes.

Who can participate?
Patients aged 18 and over who are suitable for non-surgical treatment of the Achilles tendon rupture (ATR)

What does the study involve?
Participants are randomly allocated into one of two groups. Those in group 1 are given a PRP injection. Those in group 2 are given an injection containing a placebo. Participants complete a pain diary and have four study assessments at 4,7,13 and 24 weeks, carried out by a member of the research team blind to allocation. Assessments take place over the telephone or during a hospital outpatient visit. The 24 week hospital visit includes an exercise test of ankle function. All assessments include collection of patient-reported responses to preset questions.The results may be applicable to the many other tendon and ligaments injuries.

What are the possible benefits and risks of participating?
Patients may benefit by taking part in the research as may be allocated to receive platelet rich plasma (PRP) into the Achilles tendon gap. This may increase healing. The intervention offered is an injection of the participants own platelet rich plasma and there are no known risk over receiving any injection

Where is the study run from?
John Radcliffe Hospital (UK)

When is the study starting and how long is it expected to run for?
April 2015 to November 2020

Who is funding the study?
1. NIHR/MRC Efficacy and Mechanism Evaluation Programme (UK)
2. Kadoorie Centre Trauma Research Charitable Fund (UK)

Who is the main contact?
Oxford Trauma and Emergency Care research group, oxfordtrauma@ndorms.ox.ac.uk

Study website

Contact information

Dr Oxford Trauma and Emergency Care research group
Scientific

Critical Care, Trauma and Rehabilitation (CCTR) Trials Group
Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences
University of Oxford
Oxford
OX3 7LD
United Kingdom

Phone +44 (0)1865 223115
Email oxfordtrauma@ndorms.ox.ac.uk

Study information

Study designRandomized; Interventional
Primary study designInterventional
Secondary study designRandomised controlled trial
Study setting(s)Hospital
Study typeTreatment
Participant information sheet Not available in web format, please use the contact details to request a patient information sheet
Scientific titleA pragmatic multicentre, blinded, randomised placebo-controlled trial comparing Platelet Rich Plasma injection (PRP) to placebo (imitation) injection in adults with Achilles tendon rupture. Two sub-studies are embedded within the main study to contribute to the understanding of the PRP mechanism in tendon healing.
Study acronymPATH2
Study objectivesDoes the strong PRP effect identified in basic science studies and pilot studies translate to improved tendon recovery in patients with Achilles tendon rupture when compared with control?
Ethics approval(s)NRES Committee South Central - Oxford A, 11/11/2014, ref: 14/SC/1333
Health condition(s) or problem(s) studiedTopic: Injuries and emergencies, Musculoskeletal disorders; Subtopic: Injuries and Emergencies (all Subtopics), Musculoskeletal (all Subtopics); Disease: Injuries and Emergencies, Musculoskeletal
Intervention1. Imitation injection (placebo): needle insertion into tendon rupture gap
2. Platelet Rich Plasma injection: Platelet Rich Plasma injected into Achilles tendon rupture gap
Intervention typeProcedure/Surgery
Primary outcome measureCurrent primary outcome measure as of 24/09/2019:
Muscle-tendon function, measured objectively with the limb symmetry index (LSI) in maximal work during the heel-rise endurance test (HRET) at 24 weeks post-treatment

Previous primary outcome measure:
Heel-raise Endurance Test; Timepoint(s): 24 weeks post treatment
Secondary outcome measuresCurrent secondary outcome measures as of 24/09/2019:
1. Number of heel rise repetitions and maximum heel rise height (cm) during the Heel-rise Endurance Test at 24 weeks
2. Achilles Tendon Rupture Score at 4, 7, 13 and 24 weeks and 24 months
3. Patient Specific Function Scale at 4, 7, 13 and 24 weeks and 24 months
4. Health-related quality of life assessed using the SF-12 (Acute version) at 4, 7, 13 and 24 weeks and 24 months
5. Pain diary assessed using a Visual Analogue Score daily during the first 2 weeks following treatment

Previous secondary outcome measures:
1. Achilles Tendon Rupture Score; Timepoint(s): 4, 7, 13 and 24 weeks and 24 months
2. Patient Specific Function Scale; Timepoint(s): 4, 7, 13 and 24 weeks and 24 months
3. SF-12 (Acute version); Timepoint(s): 4, 7, 13 and 24 weeks and 24 months
4. Visual Analogue Score; Timepoint(s): First 2 weeks following treatment, daily
5. Pain diary: Timepoint(s): 0-2 weeks self completion at home by patient
Overall study start date01/04/2015
Completion date21/11/2019

Eligibility

Participant type(s)Patient
Age groupAdult
Lower age limit18 Years
SexBoth
Target number of participantsPlanned Sample Size: 230; UK Sample Size: 230; Description: 20% loss to follow up incorporated in Sample size
Total final enrolment230
Key inclusion criteriaAll patients with acute Achilles tendon rupture attending outpatient trauma/orthopaedic clinic within 7 days of sustaining the injury will be eligible for inclusion in the trial. Patient is willing and able to give informed consent for participation in the study
1. Aged 18 years and over
2. Diagnosed with acute Achilles tendon rupture
3. Presenting within and receiving study treatment within 12 days post injury
4. Patients in whom the decision has been made for nonoperative treatment
5. Able (in the Investigators opinion) and willing to comply with all study requirements
6. Able to attend a PATH2 study hospital site for the 24 week follow-up
7. Patient must be Ambulatory prior to injury without the use of walking aids or assistance of another person (added 16/03/2017)
Key exclusion criteriaThe patient may not enter the study if ANY of the following apply:
1. Previous major tendon or ankle injury or deformity to either lower leg
2. History of diabetes mellitus
3. Known platelet abnormality or haematological disorder
4. Current use of systemic cortisone or an anticoagulant
5. Evidence of lower limb gangrene/ulcers or peripheral vascular disease
6. History of hepatic or renal impairment or dialysis
7. Female patients who are pregnant or breast feeding
8. Is currently receiving or has received radiation or chemotherapy within the last 3 months
9. Has inadequate venous access for drawing blood
10. Any other significant disease or disorder which, in the opinion of the investigator, may either put the participants at risk because of participation in the study, or may influence the result of the study, or the patients ability to participate in the study
11. Achilles tendon injuries at the insertion to the calcaneum or at the musculotendinous junction (added 16/030/2017)
Date of first enrolment20/07/2015
Date of final enrolment18/09/2017

Locations

Countries of recruitment

  • England
  • United Kingdom

Study participating centre

John Radcliffe Hospital
Oxford Centre
Headley Way
Headington
Oxford
OX3 9DU
United Kingdom

Sponsor information

University of Oxford
University/education

Clinical Trials and Research Governance
Manor House
John Radcliffe Hospital
Headington
Oxford
OX3 9DU
England
United Kingdom

ROR logo "ROR" https://ror.org/052gg0110

Funders

Funder type

Government

National Institute for Health Research
Government organisation / National government
Alternative name(s)
National Institute for Health Research, NIHR Research, NIHRresearch, NIHR - National Institute for Health Research, NIHR (The National Institute for Health and Care Research), NIHR
Location
United Kingdom
Kadoorie Centre Trauma Research Charitable Fund

No information available

Results and Publications

Intention to publish date30/06/2021
Individual participant data (IPD) Intention to shareNo
IPD sharing plan summaryNot expected to be made available
Publication and dissemination planCurrent publication and dissemination plan as of 16/06/2022:

MRC/NIHR EME report – December 2019
Published in peer review journal – November 2019

A summary of the trial outcome was disseminated to trial participants on relevant websites, and by email, where an email address was provided. In addition to the NIHR monograph report, the results were published in peer-reviewed medical literature, and were presented at relevant national and international conferences. The work may also contribute to any refresh of NICE guidance.

Results of an extended 2-year follow-up will be published by December 2022.

Previous publication and dissemination plan from 11/12/2020 to 16/06/2022:

MRC/NIHR EME report – December 2019
Published in peer review journal – November 2019

A summary of the trial outcome was disseminated to trial participants on relevant websites, and by email, where an email address was provided. In addition to the NIHR monograph report, the results were published in peer-reviewed medical literature, and were presented at relevant national and international conferences. The work may also contribute to any refresh of NICE guidance.

Results of an extended 2-year follow-up will be published by June 2021

Original publication and dissemination plan:

Internal MRC/NIHR EME report – June 2021
Publish in peer review journal – April 2021

A summary of the trial outcome will be disseminated to trial participants on relevant websites, and by email, where an email address is provided. In addition to the NIHR monograph report, the results will be published in peer-reviewed medical literature, and may be presented at relevant national and international conferences. The work may also contribute to any refresh of NICE guidance.
IPD sharing planThe datasets generated during and/or analysed during the current study are not expected to be made available

Study outputs

Output type Details Date created Date added Peer reviewed? Patient-facing?
Protocol article protocol 16/11/2017 Yes No
Statistical Analysis Plan statistical analysis plan 29/08/2018 No No
Results article results 20/11/2019 09/12/2020 Yes No
Results article funder report 01/11/2020 11/12/2020 Yes No
Results article results of substudy analysis 26/11/2020 11/12/2020 Yes No
Plain English results 14/06/2022 14/06/2022 No Yes
Results article 20/11/2019 14/06/2022 Yes No
HRA research summary 28/06/2023 No No
Results article 2-year follow-up 01/11/2022 11/06/2025 Yes No

Additional files

ISRCTN54992179_ResultsPlainEnglish_14Jun22.pdf

Editorial Notes

11/06/2025: Publication reference added.
07/11/2023: Contact details updated. IRAS number added.
16/06/2022: The publication and dissemination plan was updated.
14/06/2022: Publication reference added. Results in plain English uploaded as an additional file.
11/12/2020: The following changes were made to the trial record:
1. Publication references added.
2. The publication and dissemination plan was changed.
09/12/2020: Publication reference added.
04/11/2020: The following changes were made to the trial record:
1. The overall end date was changed from 30/11/2020 to 21/11/2019.
2. The total final enrolment was added.
3. The trial website was added.
24/09/2019: The following changes have been made:
1. The description of the primary outcome measure has been expanded to clarify and ensure consistency with the protocol.
2. The secondary outcome measures descriptions have been amended to add clarity and to ensure the list is comprehensive and consistent with the protocol.
3. The scientific contact has been changed.
31/08/2018: Publication reference added.
20/11/2017: Publication reference added.
19/09/2017: Recruitment end date has been updated from 30/09/2017 to 18/09/2017.
08/09/2017: The recruitment end date has been updated from 31/07/2017 to 30/09/2017. The target number of participants has been updated from 214 to 230.
20/03/2017: The overall trial end date has been updated from 30/05/2018 to 30/11/2020. In addition, Kadoorie Centre Trauma Research Charitable Fund has been added as a funder, as they are funding the extended follow up for this study.
20/03/2017: The overall trial end date has been updated from 30/11/2016 to 30/05/2018
16/03/2017: The following changed have been made to the record:
1. In the inclusion criteria, the upper age limit of 70 has been removed, the time from injury has been extended from 7 to 12 days and a further inclusion criteria has been added
2. A further exclusion criteria has been added
3. The recruitment dates have been updated from 01/04/2015 - 30/11/2016 to 20/07/2015 - 31/07/2017
18/12/2015: The sponsor details for this study was changed from the Department of of Psychiatry (Oxford) to Clinical Trials and Research Governance (John Radcliffe Hospital)