Influence Of Zoledronic Acid On Healing After Arthroskopic Repair Of Chronic Rotator Cuff Lesions A Prospective, Randomized, Placebo-Controlled Phase II Trial ZORRO

2024-519082-22-00 Protocol ZORRO Therapeutic exploratory (Phase II) Authorised, recruitment pending

Status Authorised, recruitment pending · 1 EU/EEA countries · 1 sites · Protocol ZORRO

Overview

Sponsor-declared trial summary

Phase Therapeutic exploratory (Phase II)
Status Authorised, recruitment pending
Participants planned 80
Countries 1
Sites 1

Trauma (rupture of a tendon)

Longitudinal investigation of zoledronic acid on tendon integrity via magnetic resonance imaging at six, twelve, twentyfour and sixty months after arthroscopic repair of chronic rotator cuff lesions. Null hypothesis: Adjuvant intravenous therapy with zoledronic acid does not improve tendon healing after arthroscopic re…

Key facts

Sponsor
AUVA Trauma Center Vienna
Participant type
Patients
Age range
18-64 years, 65+ years
Gender
Male and Female
Therapeutic area
Diseases [C] - Musculoskeletal Diseases [C05]
Decision date (initial)
2025-01-14
Transition trial
Yes
Low-intervention
Yes
Rare-disease indication
No
Vulnerable population
No
Funding sources
AUVA Trauma Center Vienna

External identifiers

EU CT number
2024-519082-22-00
EudraCT number
2022-001750-29
ClinicalTrials.gov
NCT03584542

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacodynamic, Therapy, Efficacy, Safety

Longitudinal investigation of zoledronic acid on tendon integrity via magnetic resonance imaging at six, twelve, twentyfour and sixty months after arthroscopic repair of chronic rotator cuff lesions.
Null hypothesis: Adjuvant intravenous therapy with zoledronic acid does not improve tendon healing after arthroscopic reconstruction of chronic rotator cuff tears compared to a control group without adjuvant therapy with zoledronic acid.

Secondary objectives 1

  1. Longitudinal assessment of the rotator cuff muscles by magnetic resonance imaging at six months, twelve months, twentyfour months and sixty months postoperatively. Furthermore, the clinical function of both shoulders will be evaluated preoperatively and longitudinally at four weeks, three months, six months, twelve months, twentyfour months and sixty months postoperatively by clinical examination, strength measurement, and specific clinical and functional questionnaires. In addition, bone metabolism will be assessed by standard blood sampling preoperatively and longitudinally at three months, six months, and twelve months postoperatively to document the efficacy of zoledronic acid in the intervention group. To investigate the muscular regeneration by zoledronic acid, special blood samples for the determination of mircro ribonucleic acids will be taken preoperatively, two days postoperatively before discharge from hospital, and three months postoperatively.

Conditions and MedDRA coding

Trauma (rupture of a tendon)

Study design 1 period

#TitleAllocationBlindingRoles blindedArms
1 A prospective, randomized, placebo-controlled phase II-trial – ZORRO
Influence of zoledronic acid on healing after arthroscopic repair of chronic rotator cuff lesions Planned total duration: 8 years. First patient first visit until last patient last visit: Q3/2022 – Q4/2030 Verum and Placebo-Group, 40 patients in each group.
Randomised Controlled Double [{"id":87594,"code":1,"name":"Subject"},{"id":87595,"code":3,"name":"Monitor"},{"id":87593,"code":2,"name":"Investigator"}] Zoledronic Acid: Aclasta® (Novartis, Basel, Switzerland) 5 mg solution for intravenous application as 100 ml infusion single-dose treatment.
physiological saline solution 0.9% (Placebo): sodium chloride (physiological saline solution 0.9%) administered as single intravenous infusion (100 ml) (placebo)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

  1.  Age between 50 and 70 years  Magnetic resonance imaging verified rotator cuff tear (within 6 months prior to surgery)  Rupture size with a maximum diameter of 3 cm  Willingness to participate in the study  Willingness to participate in a unified physiotherapy with use of a shoulder abduction pad for four weeks postoperatively

Exclusion criteria 1

  1.  Patients younger than 50 or older than 70 years of age  Pregnancy  Known allergy to zoledronic acid or other components of the medicinal product  Previous fracture of the affected shoulder  Previous surgery of the affected shoulder  Previous or existing bacterial infection of the affected shoulder  Rupture of more than two tendons in the affected shoulder (massive rotator cuff tear)  Isolated subscapularis tendon tear  Presence of glenohumeral osteoarthritis (Hamada type 3 or higher)  Diabetes mellitus (fasting glucose ≥ 126 mg/dl, HbA1C ≥ 6.5%)  Malignant tumor disease  Pathological dental status  Known disease that interferes with bone metabolism  Concomitant diseases that do not permit general anesthesia  Previous therapy with anti-osteoporotic drugs (bisphosphonates, denosumab, teriparatide)  Epilepsy  Claustrophobia  Chronic alcohol abuse  Drug abuse

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

  1.  Tendon integrity 6 months postoperative (no re-rupture/re-rupture)  Tendon integrity 12, 24 and 60 months postoperative (no re-rupture/re-rupture)

Secondary endpoints 1

  1. Fatty muscle infiltration, shoulder abduction and adduction, shoulder anteversion and retroversion, shoulder rotation internal and external, shoulder strength, pain evaluation, Constant-Murley-Score, American Shoulder and Elbow Surgeons Score, Subjective Shoulder Value

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Zoledronic Acid

SCP1097208 · ATC

Active substance
Zoledronic Acid
Substance synonyms
ZOLEDRONATE
Route of administration
INFUSION
Max daily dose
5 mg milligram(s)
Max total dose
5 mg milligram(s)
Max treatment duration
1 Day(s)
Authorisation status
Authorised
ATC code
M05BA08 — ZOLEDRONIC ACID
Marketing authorisation
-
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Placebo 1

SCP1023586 · ATC

Route of administration
INFUSION
Max daily dose
100 ml millilitre(s)
Max total dose
100 ml millilitre(s)
Max treatment duration
1 Day(s)
Authorisation status
Authorised
ATC code
B05BB01 — ELECTROLYTES
Marketing authorisation
-
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

AUVA Trauma Center Vienna

Sponsor organisation
AUVA Trauma Center Vienna
Address
Kundratstrasse 37
City
Vienna
Postcode
1120
Country
Austria

Scientific contact point

Organisation
AUVA Trauma Center Vienna
Contact name
DDr. Jakob Schanda

Public contact point

Organisation
AUVA Trauma Center Vienna
Contact name
DDr. Jakob Schanda

Locations

1 EU/EEA country · 1 investigational sites

By country

CountryMS statusPlanned subjectsSites
Austria Authorised, recruitment pending 80 1
Rest of world 0

Investigational sites

Austria

1 site · Authorised, recruitment pending
AUVA Trauma Center Vienna
Trauma Center Vienna UKH Meidling, Kundratstrasse 37, 1120, Vienna

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 5 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

TypeTitleVersion
Protocol (for publication) Clinical Study Protocol ZORRO Version final 12 07 24 1
Recruitment arrangements (for publication) Clinical Study Protocol ZORRO Version final 12 07 24 1
Subject information and informed consent form (for publication) Informed Consent ZORRO final 120724 1
Summary of Product Characteristics (SmPC) (for publication) Aclasta5 mg Infusionslosung Fachinformation September 2021 1
Synopsis of the protocol (for publication) synopsis and study design 2024 519082 22 00 AUVA 161024 1

Application history

1 submissions — initial application plus substantial / non-substantial modifications

#TypeCodeSubmittedReference MSConclusionDecision date
1 INITIAL IN 2024-10-16 Austria Acceptable
2024-12-06
2025-01-14