The ASPIRE Trial: AchilleS tendinoPathy Treated With cortIcosteRoid injEctions. (ASPIRE)

Achilles tendinopathy is a common and often persistent tendon disorder associated with pain, impaired function, and reduced participation in physical activities. Standard care consists of education, load management advice, and progressive calf-strengthening exercises, yet about half of patients remain symptomatic. Corticosteroid injections are frequently used in clinical practice, but evidence on long-term efficacy and safety remains inconclusive. The ASPIRE trial is a multicentre, randomized, double-blind, placebo-controlled phase III trial evaluating whether 1-3 ultrasound-guided peritendinous corticosteroid injections added to standard care are safe and more effective than placebo injections plus standard care in adults with chronic midportion Achilles tendinopathy. The primary outcomes are change in VISA-A score over 1 year and incidence of full-thickness Achilles tendon rupture during 1-year follow-up.

Study Overview

• Status: Recruiting
• Conditions: Achilles Tendinopathy (AT)
• Intervention / Treatment: Other: Standard care; Drug: Depo-Medrol (methylprednisolone acetate 40 mg) combined with lidocaine; Drug: placebo injections consisting of lidocaine only

Detailed Description

The ASPIRE trial is designed to address uncertainty regarding peritendinous corticosteroid injections as a second-line treatment for chronic midportion Achilles tendinopathy. Participants are adults aged 18-65 years with clinically diagnosed and ultrasonographically confirmed chronic midportion Achilles tendinopathy, persistent symptoms for at least 6 months, and ongoing complaints despite standard care including at least 3 months of exercise therapy. Participants are randomized 1:1 to receive either 1-3 ultrasound-guided peritendinous injections of methylprednisolone acetate 40 mg plus lidocaine, or 1-3 ultrasound-guided placebo injections with lidocaine only. All participants receive the same standard care consisting of education, load management advice, and a structured progressive calf-muscle strengthening exercise programme supported by an online website. Follow-up includes clinical assessments, questionnaires, ultrasound imaging, and functional testing at baseline, 3 months, and 1 year, with additional online questionnaires up to 10 years.

• Study Type: Interventional
• Enrollment (Estimated): 276
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Kristel van Abswoude, MD; Phone Number: +31 6 49326353; Email: aspire@erasmusmc.nl

Study Locations

• Netherlands
  • Rotterdam, Netherlands
    • Recruiting
    • Erasmus MC
    • Contact: k van Abswoude, MD; Phone Number: +31 6 49326353; Email: aspire@erasmusmc.nl
    • Contact: R.J de Vos, MD/PhD; Phone Number: +31 10 7040136; Email: r.devos@erasmusmc.nl

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age 18-65 years
• Clinically diagnosed midportion Achilles tendinopathy confirmed by ultrasound
• Symptoms for at least 6 months
• Persistent complaints despite standard care, including education, load management advice and at least 3 months of exercise therapy / exercise programme

Exclusion Criteria:

• • Clinical suspicion of insertional Achilles tendinopathy

  • Clinical suspicion of Achilles tendon rupture
  • Clinical suspicion of plantar flexor tenosynovitis
  • Clinical suspicion of sural nerve pathology
  • Clinical suspicion of peroneal tendon subluxation or peroneal tendinopathy
  • Clinical suspicion of posterior ankle impingement syndrome
  • Suspected systemic/inflammatory disorder as cause of symptoms
  • Any condition preventing participation in active exercise programme
  • History of Achilles tendon rupture of index tendon
  • Previous local corticosteroid injection on index Achilles tendon
  • Previous surgery on index Achilles tendon
  • Refusal to undergo one of the study treatments
  • Local skin infection, suspected systemic infection with fever, or other medical condition compromising injection safety
  • Vitamin K antagonist use with INR >3.0 within 3 days before injection or unknown INR
  • Current pregnancy or breastfeeding
  • Medication-induced tendon pathology (quinolones or statins related to symptom onset)
  • Inability to provide informed consent
  • Participation in another concomitant interventional programme for Achilles tendinopathy
  • Known hypersensitivity or allergy to Depo-Medrol or Lidocaine
  • Participants with unstable or poorly controlled diabetes mellitus may be excluded at investigator discretion for safety reasons.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Corticosteroid and Lidocaine Injection + Standard Care; Participants receive 1-3 ultrasound-guided peritendinous injections of Depo-Medrol (methylprednisolone acetate 40 mg) combined with lidocaine, in addition to standard care consisting of education, load management advice, and a structured progressive calf-strengthening exercise programme. All participants receive one injection at baseline; up to two additional injections may be given within the first 8 weeks at intervals of 4 weeks if predefined criteria are met.	Other: Standard care; Education, load management advice, and a structured progressive calf-muscle strengthening exercise programme supported by an online website.; Drug: Depo-Medrol (methylprednisolone acetate 40 mg) combined with lidocaine; Participants receive 1-3 ultrasound-guided peritendinous injections of Depo-Medrol (methylprednisolone acetate 40 mg) combined with lidocaine.; Other Names: Drug: Methylprednisolone acetate 40 mg + Lidocaine 10 mg; Depo-Medrol + Lidocaine
Placebo Comparator: Placebo Injection + Standard Care; Participants receive 1-3 ultrasound-guided peritendinous placebo injections consisting of lidocaine only, in addition to standard care consisting of education, load management advice, and a structured progressive calf-strengthening exercise programme. All participants receive one injection at baseline; up to two additional injections may be given within the first 8 weeks at intervals of at least 4 weeks if predefined criteria are met.	Other: Standard care; Education, load management advice, and a structured progressive calf-muscle strengthening exercise programme supported by an online website.; Drug: placebo injections consisting of lidocaine only; Participants receive 1-3 ultrasound-guided peritendinous placebo injections consisting of lidocaine onl; Other Names: Placebo injection; Drug: Lidocaine 10 mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in disability and symptoms measured with the VISA-A questionnaire.	Change in disability and symptoms during 1-year follow-up, measured with the validated Victorian Institute of Sport Assessment-Achilles (VISA-A) questionnaire, scored from 0 to 100.	Baseline to 1 year follow-up (timepoints: Baseline, 4 weeks, 8 weeks, 3 months, 6 months, 9 months, and 1-year).
Incidence of full-thickness Achilles tendon rupture	Incidence of full-thickness Achilles tendon ruptures during 1-year follow-up, confirmed by medical records or clinical tests and imaging.	During 1-year follow-up

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Minor corticosteroid side effects / corticosteroid safety indicators	Body mass (kg)	baseline, 3 months, 6 months, 9 months, and 1 year.
Tendon-related symptoms and disability	TENDINopathy Severity Assessment - Achilles (TENDINS-A) score. 0-100; 0= worts, 100= best	baseline, 3 months, 6 months, 9 months, and 1 year
Pain outcomes	Pain during activity, measured on a VAS 0-10 scale	Assessed at baseline, 3 months, 6 months, 9 months, and 1 year
Global perceived improvement	Global Rating of Change (GROC), 11-point scale	Assessed at 3 months, 6 months, 9 months, and 1 year
Physical function / functional test outcomes	Maximum VAS pain (0-10) during or after palpation of the Achilles tendon	Assessed at baseline, 3 months, and 1 year
Health-related quality of life	EuroQol-5 Dimensions, 5 Levels questionnaire (EQ-5D-5L)	Assessed at baseline, 3 months, 6 months, 9 months, and 1 year
Return to sport / physical activity level	Return to desired sports participation using a 7-point scale	Assessed at baseline, 3 months, 6 months, 9 months, and 1 year.
Healthcare use	Medical Consumption Questionnaire (iMCQ) for healthcare use The economic evaluation will be published separately.	Assessed at baseline, 3 months, 6 months, 9 months, and 1 year
Imaging outcomes: tendon structure	Ultrasound and ultrasound tissue characterisation of Achilles tendon where the degree of collagen disorganisation is assed using: echo types I, echo types II, echo types III, echo types IV, combined percentage echo types I + II	Assessed at baseline, 3 months, and 1 year
Imaging outcomes: neovascularisation / Doppler flow	percentage of Doppler flow within the color box, quantified with the Surface Area Quantification (SAQ) method	Assessed at baseline, 3 months, and 1 year
Minor corticosteroid side effects / corticosteroid safety indicators	Body fat percentage	baseline, 3 months, and 1 year.
Minor corticosteroid side effects / corticosteroid safety indicators	Waist circumference (cm)	baseline, 3 months, and 1 year
Minor corticosteroid side effects / corticosteroid safety indicators	Visible skin abnormalities at the injection site	baseline, 3 months, and 1 year.
Minor corticosteroid side effects / corticosteroid safety indicators	Hot flushes (5-point scale)	baseline, 3 months, 6 months, 9 months, and 1 year.
Minor corticosteroid side effects / corticosteroid safety indicators	Menstrual disturbances (if applicable, 5-point scale)	baseline, 3 months, 6 months, 9 months, and 1 year
Minor corticosteroid side effects / corticosteroid safety indicators	Sleep disturbances (5-point scale)	baseline, 3 months, 6 months, 9 months, and 1 year.
Minor corticosteroid side effects / corticosteroid safety indicators	Appetite (5-point scale)	baseline, 3 months, 6 months, 9 months, and 1 year.
Physical function / functional test outcomes	Maximum VAS pain (0-10) during or after 5 single-leg heel rises	Assessed at baseline, 3 months, and 1 year
Physical function / functional test outcomes	Maximum VAS pain (0-10) during or after 5 hops	Assessed at baseline, 3 months, and 1 year
Physical function / functional test outcomes	Heel Rise Endurance Test (HRET) - repetitions	Assessed at baseline, 3 months, and 1 year
productivity loss	Institute for Medical Technology Assessment Productivity Cost Questionnaire (iPCQ for productivity loss). The economic evaluation will be published separately	Assessed at baseline, 3 months, 6 months, 9 months, and 1 year
Imaging outcomes: tendon structure on ultrasound	tendon volume (cubic centimeters)	Assessed at baseline, 3 months, and 1 year
Imaging outcomes: tendon structure on ultrasound	maximum cross-sectional area (square cm)	Assessed at baseline, 3 months, and 1 year
Imaging outcomes: tendon structure on ultrasound	tendon maximum diameter (cm)	Assessed at baseline, 3 months, and 1 year
Pain outcomes	Pain after activity, measured on a VAS 0-10 scale	Assessed at baseline, 3 months, 6 months, 9 months, and 1 year

Collaborators and Investigators

• Sponsor: Erasmus Medical Center
• Collaborators: UMC Utrecht; ZonMw: The Netherlands Organisation for Health Research and Development; Isala; Gelderse Vallei Hospital; Bergman Clinics; Haaglanden Medical Centre; Amsterdam UMC; Dutch Association of Sports Medicine (VSG); Dutch Orthopaedic Association (NOV); Dutch College of General Practitioners (NHG Musculoskeletal Care); International Trial Advisory Board; Patient Panel
• Investigators: Principal Investigator: Robert Jan de Vos, MD, PhD, Erasmus Medical Centre

Study record dates

Study Major Dates

• Study Start (Actual): June 3, 2026
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): October 31, 2028

Study Registration Dates

• First Submitted: June 2, 2026
• First Submitted That Met QC Criteria: June 10, 2026
• First Posted (Actual): June 16, 2026

Study Record Updates

• Last Update Posted (Actual): June 16, 2026
• Last Update Submitted That Met QC Criteria: June 10, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Lidocaine; Exercise therapy; Depo-Medrol; Ultrasound-guided injection; Corticosteroid injection; VISA-A; Placebo injection; Methylprednisolone acetate
• Additional Relevant MeSH Terms: Health Services Administration; Health Care Quality, Access, and Evaluation; Organic Chemicals; Quality of Health Care; Polycyclic Compounds; Quality Indicators, Health Care; Anilides; Amides; Aniline Compounds; Amines; Acetanilides; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Pregnadienetriols; Methylprednisolone; Prednisolone; Methylprednisolone Acetate; Lidocaine; Standard of Care
• Other Study ID Numbers: MEC-2026-0210; 2025-524057-13-00 (Ctis); ZonMw grant number: 1014102241 (Other Identifier: ZonMw)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: upon reasonable request.
• IPD Sharing Time Frame: as yet undetermined
• IPD Sharing Access Criteria: as yet undetermined
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No