PATH2: Platelet rich plasma in Achilles tendon healing

ISRCTN	ISRCTN54992179
DOI	https://doi.org/10.1186/ISRCTN54992179
ClinicalTrials.gov (NCT)	NCT02302664
Clinical Trials Information System (CTIS)	Nil known
Integrated Research Application System (IRAS)	146684
Protocol serial number	17850, IRAS 146684
Sponsor	University of Oxford
Funders	National Institute for Health Research, Kadoorie Centre Trauma Research Charitable Fund

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

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

Primary study design	Interventional
Study design	Randomized; Interventional
Secondary study design	Randomised controlled trial
Study type	Participant information sheet
Scientific title	A 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 acronym	PATH2
Study objectives	Does 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) studied	Topic: Injuries and emergencies, Musculoskeletal disorders; Subtopic: Injuries and Emergencies (all Subtopics), Musculoskeletal (all Subtopics); Disease: Injuries and Emergencies, Musculoskeletal
Intervention	1. Imitation injection (placebo): needle insertion into tendon rupture gap 2. Platelet Rich Plasma injection: Platelet Rich Plasma injected into Achilles tendon rupture gap
Intervention type	Procedure/Surgery
Primary outcome measure(s)	Current 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
Key secondary outcome measure(s)	Current 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
Completion date	21/11/2019

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	All
Target sample size at registration	230
Total final enrolment	230
Key inclusion criteria	All 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 criteria	The 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 enrolment	20/07/2015
Date of final enrolment	18/09/2017

Locations

Countries of recruitment

United Kingdom
England

Study participating centre

John Radcliffe Hospital

Oxford Centre
Headley Way
Headington
Oxford
OX3 9DU
United Kingdom

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not expected to be made available
IPD sharing plan	The 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?
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
Results article		20/11/2019	14/06/2022	Yes	No
Results article	2-year follow-up	01/11/2022	11/06/2025	Yes	No
Protocol article	protocol	16/11/2017		Yes	No
HRA research summary			28/06/2023	No	No
Participant information sheet	Participant information sheet	11/11/2025	11/11/2025	No	Yes
Plain English results		14/06/2022	14/06/2022	No	Yes
Statistical Analysis Plan	statistical analysis plan	29/08/2018		No	No
Study website	Study website	11/11/2025	11/11/2025	No	Yes

Additional files

ISRCTN54992179_ResultsPlainEnglish_14Jun22.pdf: Plain English results

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)