Safety of ibuprofen after major orthopaedic surgeries

2022-502502-32-00 Phase III and Phase IV (Integrated) Ongoing, recruitment ended

Start 17 Apr 2023 · Status Ongoing, recruitment ended · 1 EU/EEA countries · 9 sites

Overview

Sponsor-declared trial summary

Phase Phase III and Phase IV (Integrated)
Status Ongoing, recruitment ended
Participants planned 2,904
Countries 1
Sites 9

Hip and knee arthroplasties

We aim to assess the beneficial and harmful effects of an eight day postoperative treatment with ibuprofen, a non-selective NSAID and one of the most used non-opioid analgesics, after elective hip and knee arthroplasties.

Key facts

Sponsor
Slagelse Hospital, Slagelse Hospital
Participant type
Patients
Age range
18-64 years, 65+ years
Gender
Male and Female
Therapeutic area
Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Anesthesia and Analgesia [E03]
Trial duration
17 Apr 2023 → ongoing
Decision date (initial)
2023-03-17
Transition trial
No
Low-intervention
Yes
Rare-disease indication
No
Vulnerable population
No

External identifiers

EU CT number
2022-502502-32-00
ClinicalTrials.gov
NCT05575700

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

We aim to assess the beneficial and harmful effects of an eight day postoperative treatment with ibuprofen, a non-selective NSAID and one of the most used non-opioid analgesics, after elective hip and knee arthroplasties.

Conditions and MedDRA coding

Hip and knee arthroplasties

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

  1. Scheduled for planned primary hip or knee arthroplasty, including hemiarthroplasty.
  2. Age ≥ 18 years.
  3. Planned perioperative pain treatment with NSAID, decided by the clinical doctor.
  4. Negative urine Human Chorionic Gonadotropin (hCG) pregnancy test and use of anti-conception for women in fertile age.
  5. Written informed consent.

Exclusion criteria 2

  1. Patients unable to understand or speak Danish.
  2. Allergy to, or contraindications against ibuprofen, including heart insufficient (NYHA IV), severe thrombocytopenia (< 50 x 10^9/l), asthma triggered by NSAID, or known renal impairment (eGFR < 60 ml/min), previous ulcer due to NSAID treatment.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

  1. A composite outcome of either death, acute myocardial infarction, stroke, pulmonary embolism, deep venous thrombosis, renal failure, major bleeding, re-operation, gastrointestinal ulcer, or readmission within 90 days postoperatively.

Secondary endpoints 4

  1. Hospital free days within 90 days postoperatively.
  2. A composite outcome of ibuprofen related adverse events based on eight-day postoperative diary: pain or discomfort from the epigastrium, reflux, diarrhoea.
  3. A composite outcome of opioid related adverse events based on eight-day postoperative diary: nausea, vomiting, constipation, sedation, headache, mood changes, mouth dryness.
  4. Health related quality of life questionnaire via EQ-5D-5L after 90 days and one year postoperatively.

Investigational products

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

Test 1

Ibuprofen 400 mg, tabletten

PRD1834569 · Product

Active substance
Ibuprofen
Pharmaceutical form
COATED TABLET
Route of administration
ORAL
Max daily dose
1200 mg milligram(s)
Max total dose
9200 mg milligram(s)
Max treatment duration
8 Day(s)
Authorisation status
Authorised
ATC code
M01AE01 — IBUPROFEN
Marketing authorisation
RVG 18544
MA holder
GENRX B.V.
MA country
Netherlands
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Placebo 1

Identical capsule

N/A · Product

Other product name
N/A
Pharmaceutical form
N/A
ATC code
N/A — N/A
Marketing authorisation
N/A
MA holder
N/A
MA country
Iceland
Paediatric formulation
No

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Slagelse Hospital

Sponsor organisation
Slagelse Hospital
Address
Ingemannsvej 18
City
Slagelse
Postcode
4200
Country
Denmark

Scientific contact point

Organisation
Slagelse Hospital
Contact name
Daniel Hägi-Pedersen

Public contact point

Organisation
Slagelse Hospital
Contact name
Daniel Hägi-Pedersen

Third parties 3

OrganisationCity, countryDuties
Odense University Hospital
ORG-100007716
 Odense C, Denmark On site monitoring
Aarhus University
ORG-100028380
 Aarhus C, Denmark On site monitoring
Frederiksberg Hospital
ORG-100028217
 Frederiksberg, Denmark On site monitoring

Slagelse Hospital

Sponsor organisation
Slagelse Hospital
Address
Ingemannsvej 18
City
Slagelse
Postcode
4200
Country
Denmark

Locations

1 EU/EEA country · 9 investigational sites

By country

CountryMS statusPlanned subjectsSites
Denmark Ongoing, recruitment ended 2,904 9
Rest of world — 0 —

Investigational sites

Denmark

9 sites · Ongoing, recruitment ended
Zealand University Hospital
Anaesthesiology, Lykkebaekvej 1, 4600, Koege
Vejle Hospital
Orthopaedic surgery, Kabbeltoft 25, 7100, Vejle
Aalborg University Hospital
Orthopaedic surgery, Hoejgaardsvej 11, 9640, Farsoe
Næstved Hospital
Anaesthesiology, Ringstedgade 61, 4700, Næstved
Odense University Hospital
Orthopaedic Surgery and Traumatology, Baagoees Alle 15, 5700, Svendborg
Gentofte Hospital
Anaesthesiology, Kildegårdsvej 28, 2900, Hellerup
Hillerod Hospital
Anaesthesiology, Dyrehavevej 29, 3400, Hillerød
Regionshospitalet Silkeborg
Orthopaedic surgery, Falkevej 1A, 8600, Silkeborg
Bispebjerg Hospital
Anaesthesia and Intensive Care, Bispebjerg Bakke 23, 2400, Copenhagen Nv

Country notifications

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

Country Trial startTrial end Recruitment startRecruitment end Early termination
Denmark 2023-04-17 2023-04-18 2025-05-19

Results and documents

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

Documents 14 files

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

TypeTitleVersion
Protocol (for publication) PERISAFE_trial_Protocol_2022-502502-32-00 1.3
Protocol (for publication) PERISAFE_trial_Protocol_2022-502502-32-00_TC 1.3
Recruitment arrangements (for publication) PERISAFE_trial_Experimental consent process_2022-502502-32-00 1
Recruitment arrangements (for publication) PERISAFE_trial_Recruitment arrangements_2022-502502-32-00 1.1
Recruitment arrangements (for publication) PERISAFE_trial_Recruitment arrangements_2022-502502-32-00_TC 1.1
Subject information and informed consent form (for publication) Danish-EQ-5D-5L questionnaire 1
Subject information and informed consent form (for publication) PERIAFE_trial_Informed consent form_standard VEK aug 2016_PERISAFE_2022-502502-32-00 1
Subject information and informed consent form (for publication) PERISAFE_trial_Dine rettigheder som forsgsperson i forsg med medicin_2022-502502-32-00 1
Subject information and informed consent form (for publication) PERISAFE_trial_eigth-day patient diary_2022-502502-32-00 1
Subject information and informed consent form (for publication) PERISAFE_trial_queastionnaire day 14_2022-502502-32-00 1.1
Subject information and informed consent form (for publication) PERISAFE_trial_queastionnaire day 14_2022-502502-32-00_TC 1.1
Subject information and informed consent form (for publication) PERISAFE_trial_Subject information originial language_2022-502502-32-00 1.3
Subject information and informed consent form (for publication) PERISAFE_trial_Subject information originial language_2022-502502-32-00_TC 1.3
Summary of Product Characteristics (SmPC) (for publication) PERISAFE_trial_SmPC_product summary ibumetin_2022-502502-32-00 1

Application history

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

#TypeCodeSubmittedReference MSConclusionDecision date
1 INITIAL IN 2022-12-14 Denmark Acceptable
2023-03-13
 2023-03-17
2 SUBSTANTIAL MODIFICATION SM-1 2023-03-20 Denmark Acceptable 2023-03-29
3 NON SUBSTANTIAL MODIFICATION NSM-2 2023-05-09 Denmark Acceptable 2023-05-09
4 SUBSTANTIAL MODIFICATION SM-2 2025-01-08 Denmark Acceptable
2025-02-25
 2025-03-31

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