Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Trials
Published in: Trials 1/2018

Open Access 01-12-2018 | Update

Platelet-rich plasma in Achilles tendon healing 2 (PATH-2) trial: statistical analysis plan for a multicentre, double-blinded, parallel-group, placebo-controlled randomised clinical trial

Authors: Michael M. Schlüssel, David J. Keene, Susan Wagland, Joseph Alsousou, Sarah E. Lamb, Keith Willett, Susan J. Dutton, on behalf of the PATH-2 Trial Study Group

Published in: Trials | Issue 1/2018

Login to get access

Abstract

Background

There has been a recent steep growth in platelet-rich plasma (PRP) use for musculoskeletal conditions, but findings from high quality clinical trial data are lacking in the literature. Here, we describe the statistical analysis plan (SAP) for the Platelet-rich plasma in Achilles Tendon Healing 2 (PATH-2) trial.

Methods

PATH-2 is a pragmatic, parallel-group, multi-centre, double-blinded, randomised, placebo-controlled, superiority trial. The study aims to evaluate the clinical efficacy of PRP in acute Achilles tendon rupture in terms of muscle-tendon function. Patients are identified in the orthopaedic/trauma outpatient clinic. The primary outcome is muscle-tendon work capacity from the Heel Rise Endurance Test result, expressed as the Limb Symmetry Index (work, in joules), at 24 weeks post randomisation. Multivariate linear regression adjusting for the stratification factors (centre and age) and additional prognostic factors will be used to investigate the adjusted effect of the intervention. The analysis will be by modified intention-to-treat. Sensitivity analysis will assess the internal validity of the trial results by performing a per-protocol analysis. Safety will be summarised by treatment arm for all patients who started treatment. Secondary patient-reported outcome measures will be analysed using linear mixed effects models to allow all data collected at all follow-up points to be considered. Missing data will be summarised and reported by treatment arm. Missing data imputation will be performed, if appropriate.

Discussion

The PATH-2 trial will be reported in accordance with the CONSORT statement. This SAP publication will avoid bias arising from prior knowledge of the study results. Any changes or deviations from the current SAP will be described and justified in the final report.

Trial registration

ISRCTN registry: ISRCTN54992179, assigned 12 January 2015. ClinicalTrials.gov: NCT02302664, received 18 November 2014. UK Clinical Research Network Study Portfolio Database: ID 17850.
Appendix
Available only for authorised users
Literature
1.
2.
Sheth U, Simunovic N, Klein G, et al. Efficacy of autologous platelet-rich plasma use for orthopaedic indications: a meta-analysis. J Bone Joint Surg Am. 2012;94:298–307.CrossRefPubMed
3.
Alsousou J, Keene DJ, Hulley PA, et al. Platelet rich Plasma in Achilles Tendon Healing 2 (PATH-2) trial: protocol for a multicentre, participant and assessor-blinded, parallel group randomised clinical trial comparing platelet-rich plasma (PRP) injection versus placebo injection for Achilles tendon rupture. BMJ Open. 2017;7:e018135.CrossRefPubMedPubMedCentral
4.
Nilsson-Helander K, Silbernagel KG, Thomeé R, et al. Acute Achilles tendon rupture: a randomized, controlled study comparing surgical and nonsurgical treatments using validated outcome measures. Am J Sports Med. 2010;38:2186–93.CrossRefPubMed
5.
Brown S, Thorpe H, Hawkins K, et al. Minimization – reducing predictability for multicentre trials whilst retaining balance within Centre. Stat Med. 2005;24:3715–27.CrossRefPubMed
6.
James KE, Lee KK, Kraemer HK, et al. An index for assessing blindness in a multicenter clinical trial: disulfiram for alcohol cessation-a VA cooperative study. Stat Med. 1990;15:1421–34.CrossRef
7.
Bang H, Ni L, Davis CE. Assessment of blinding in clinical trial. Control Clin Trials. 2004;25:143–56.CrossRefPubMed
8.
White IR, Royston P, Wood AM. Multiple imputation using chained equations: issues and guidance for practice. Stat Med. 2011;30:377–99.CrossRefPubMed
9.
Rubin DB. Multiple Imputation for Nonresponse in Surveys. New York: Wiley; 2014.
10.
11.
Schulz KF, Altman DG, Moher D, et al. Statement: updated guidelines for reporting parallel group randomised trials. BMJ. 2010;2010:c332.CrossRef
12.
Boutron I, Moher D, Altman DG, et al. Extending the CONSORT statement to randomized trials of nonpharmacologic treatment: explanation and elaboration. Ann Intern Med. 2008;148:295–309.CrossRefPubMed
13.
14.
Hoffmann TC, Glasziou PP, Boutron I, et al. Better reporting of interventions: template for intervention description and replication (TIDieR) checklist and guide. BMJ. 2014;348:g1687.CrossRefPubMed
15.
Hawker GA, Mian S, Kendzerska T, et al. Measures of adult pain: visual analog scale for pain (VAS pain), numeric rating scale for pain (NRS pain), McGill pain questionnaire (MPQ), short-form McGill pain questionnaire (SF-MPQ), chronic pain grade scale (CPGS), short Form-36 bodily pain scale (SF-36 BPS), and measure of intermittent and constant osteoarthritis pain (ICOAP). Arthritis Care Res. 2011;63(S11):S240–S52.CrossRef
16.
Nilsson-Helander K, Thomeé R, Grävare-Silbernagel K, et al. The Achilles tendon Total Rupture Score (ATRS): development and validation. Am J Sports Med. 2007;35:421–6.CrossRefPubMed
17.
Horn KK, Jennings S, Richardson G, et al. The Patient-Specific Functional Scale: psychometrics, Clinimetrics, and application as a clinical outcome measure. J Orthop Sports Phys Ther. 2012;42:30–42.CrossRefPubMed
18.
Stratford P. Assessing disability and change on individual patients: a report of a patient specific measure. Physiother Can. 1995;47:258–63.CrossRef
19.
Ware JE Jr, Kosinski M, Keller SD. A 12-item short-form health survey: construction of scales and preliminary tests of reliability and validity. Med Care. 1996;34:220–33.CrossRefPubMed
Metadata
Title
Platelet-rich plasma in Achilles tendon healing 2 (PATH-2) trial: statistical analysis plan for a multicentre, double-blinded, parallel-group, placebo-controlled randomised clinical trial
Authors
Michael M. Schlüssel
David J. Keene
Susan Wagland
Joseph Alsousou
Sarah E. Lamb
Keith Willett
Susan J. Dutton
on behalf of the PATH-2 Trial Study Group
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Trials / Issue 1/2018
Electronic ISSN: 1745-6215
DOI
https://doi.org/10.1186/s13063-018-2840-z

Other articles of this Issue 1/2018

Trials 1/2018 Go to the issue

Research

Hospital recruitment for a pragmatic cluster-randomized clinical trial: Lessons learned from the COMPASS study

Study protocol

Physical activity as treatment for alcohol use disorders (FitForChange): study protocol for a randomized controlled trial

Research

A cluster randomised trial of a classroom communication resource program to change peer attitudes towards children who stutter among grade 7 students

Research

Exploring factors associated with views on sharing of certain interim trial result measures by the data safety monitoring board (DSMB) with non-DSMB members

Study protocol

Optimizing treatment protocols for spinal manipulative therapy: study protocol for a randomized trial

Study protocol

‘Test n Treat (TnT)’– Rapid testing and same-day, on-site treatment to reduce rates of chlamydia in sexually active further education college students: study protocol for a cluster randomised feasibility trial