Zoledronate Early to Hip Fractures Patients – safe and effective? A Randomized controlled double-blinded treatment strategy trial on Zoledronate in hip fracture patients: The ZEBRA trial

2023-510198-32-00 Therapeutic use (Phase IV) Ongoing, recruitment ended

Start 1 Dec 2021 · Status Ongoing, recruitment ended · 1 EU/EEA countries · 3 sites

Overview

Sponsor-declared trial summary

Phase Therapeutic use (Phase IV)
Status Ongoing, recruitment ended
Participants planned 300
Countries 1
Sites 3

Hip fracture

To have zoledronate within 5 days (early) after hip fracture surgery is non-inferior to have zoledronate 3 months (late) after hip fracture surgery measured by the level of bone suppression estimated by the bone turnover marker P1NP 12 months after zoledronate treatment.

Key facts

Sponsor
Oslo University Hospital HF
Participant type
Patients
Age range
18-64 years, 65+ years
Gender
Male and Female
Therapeutic area
Diseases [C] - Musculoskeletal Diseases [C05]
Trial duration
1 Dec 2021 → ongoing
Decision date (initial)
2024-06-19
Transition trial
Yes
Low-intervention
No
Rare-disease indication
No
Vulnerable population
No

External identifiers

EU CT number
2023-510198-32-00
EudraCT number
2020-000638-17
ClinicalTrials.gov
NCT20122234

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

To have zoledronate within 5 days (early) after hip fracture surgery is non-inferior to have zoledronate 3 months (late) after hip fracture surgery measured by the level of bone suppression estimated by the bone turnover marker P1NP 12 months after zoledronate treatment.

Conditions and MedDRA coding

Hip fracture

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

  1. One low energy hip fracture
  2. Surgery within 72 hours
  3. >50 years old - Women age 50-60 must be postmenopausal or not pregnant
  4. Acceptable kidney function (estimated GFR >35) and calcium levels
  5. Fit to complete the follow-up judged by the recruiting physician
  6. Signed informed consent by the patient or the next of kin

Exclusion criteria 7

  1. Metal in the opposite hip
  2. More than one acute fracture (concomitant fracture in addition to hip fracture)
  3. Anti-osteoporosis treatment with bisphosphonates, denosumab, teriparatid, abaloparatid or romosozumab within the last 10 years
  4. Glucocorticoid therapy, treatment with gnRH-analogs, aromatase-inhibitors, primary skeletal cancer or metastasis to the skeleton
  5. Too sick to receive treatment with zoledronate judged by the recruiting or treating physician
  6. Any other contraindication listed on the SmPC of the IMP(s) including pregnancy
  7. Participating in another trial that might affect the current study

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

  1. Difference between the two groups in proportion of patients having P1NP>35µg/L 12 months after treatment with zoledronate

Secondary endpoints 11

  1. Grade of early mobilization measured by CAS score in hospital/at discharge from hospital
  2. Number of patients with delirium assessed by 4AT in hospital
  3. Difference between the two groups in proportion of patients having CTX>0.28µg/L 12 months after treatment with zoledronate
  4. Change in BMD 12 months after treatment with zoledronate
  5. Grade of mobilization and rehabilitation 3 months after fracture measured by TUG test
  6. Number of patients with fever (T> 38’C) in hospital
  7. Number of patients treated with antibiotics in hospital
  8. Time to discharge from hospital after admission and after the hip fracture surgery
  9. Time to and number of readmissions to hospital (any department)
  10. Time to and number of new fractures
  11. Time to and number of deaths

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
INTRAVENIOUS 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
INTRAVENIOUS INFUSION
Max daily dose
40 millilitre(s)/kilogram
Max total dose
40 millilitre(s)/kilogram
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

Oslo University Hospital HF

Sponsor organisation
Oslo University Hospital HF
Address
Taarnbygget, Kirkeveien 166 Kirkeveien 166
City
Oslo
Postcode
0450
Country
Norway

Scientific contact point

Organisation
Oslo University Hospital HF
Contact name
Lene Bergendal Solberg

Public contact point

Organisation
Oslo University Hospital HF
Contact name
Division of ortopaedic surgery

Locations

1 EU/EEA country · 3 investigational sites

By country

CountryMS statusPlanned subjectsSites
Norway Ongoing, recruitment ended 300 3
Rest of world 0

Investigational sites

Norway

3 sites · Ongoing, recruitment ended
Diakonhjemmet Sykehus AS
Rheumatology, Diakonveien 12, 0370, Oslo
Oslo University Hospital HF
Ortopaedic, Taarnbygget, Kirkeveien 166, Oslo
Vestre Viken HF
Ortopaedic, Sogneprest Munthe-kaas vei 100, Bærum sykehus, Gjettum

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Country Trial startTrial end Recruitment startRecruitment end Early termination
Norway 2021-12-01 2021-12-01 2025-03-31

Application history

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

#TypeCodeSubmittedReference MSConclusionDecision date
1 INITIAL IN 2024-05-15 Norway Acceptable
2024-06-18
2024-06-19