Efficacy of perioperative duloxetine in patients at high risk for developing chronic postsurgical pain after inguinal hernia repair: a multicenter randomized controlled trial

2023-505860-12-00 Protocol ICI21/00006l Therapeutic confirmatory (Phase III) Ongoing, recruiting

Start 26 Jun 2024 · Status Ongoing, recruiting · 1 EU/EEA countries · 13 sites · Protocol ICI21/00006l

Overview

Sponsor-declared trial summary

Phase Therapeutic confirmatory (Phase III)
Status Ongoing, recruiting
Participants planned 294
Countries 1
Sites 13

Chronic postsurgical pain after inguinal hernia repair

To determine the efficacy of duloxetine versus placebo in reducing the incidence of CPSP at 4 months in patients at high risk of this complication

Key facts

Sponsor
Parc De Salut Mar
Participant type
Patients
Age range
18-64 years, 65+ years
Gender
Male and Female
Therapeutic area
Diseases [C] - Nervous System Diseases [C10]
Trial duration
26 Jun 2024 → ongoing
Decision date (initial)
2023-09-15
Transition trial
No
Low-intervention
No
Rare-disease indication
No
Vulnerable population
No
Funding sources
Instituto de Salud Carlos III

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Therapy

To determine the efficacy of duloxetine versus placebo in reducing the incidence of CPSP at 4 months in patients at high risk of this complication

Secondary objectives 2

  1. To compare the characteristics, intensity, and impact of CPSP on quality of life in the intervention and control groups.
  2. To assess safety by comparing the rates of adverse effects of perioperative duloxetine and placebo for the primary prevention of CPSP

Conditions and MedDRA coding

Chronic postsurgical pain after inguinal hernia repair

VersionLevelCodeTermSystem organ class
20.1 LLT 10049475 Chronic pain 10018065

Study design 1 period

#TitleAllocationBlindingRoles blindedArms
1 All the clinical trial
Patients will be randomized after enrolling in the study to Arm A or B. Arm A: Treatment with Duloxetine Arm B: Placebo
 Randomised Controlled Double [{"id":174430,"code":1,"name":"Subject"},{"id":174429,"code":2,"name":"Investigator"}] Duloxetine 30mg: Duloxetine 30mg once a day. 1 week prior to surgery and 2 weeks post-surgery
Placebo: Placebo capsule once a day. 1 week prior to surgery and 2 weeks post-surgery

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 2

  1. Men that live in Spain during the entire trial and who are scheduled for open inguinal hernia repair (inpatient or outpatient procedures).
  2. Risk of post-surgical pain chronification ≥ 16% using the GENDOLCAT risk scale.

Exclusion criteria 27

  1. Age under 18 years
  2. Patients who in the recruiter’s opinion have insufficient knowledge of Spanish to understand the trial
  3. Patients who are currently being treated with duloxetine
  4. Patients with known allergy to duloxetine or hypersensitivity to any of the excipients
  5. Serious renal failure (creatinine clearance >30 ml/min in blood test during 3 months before surgery)
  6. Patients requiring reoperation because of surgical complications
  7. Transplanted patients
  8. History of coronary artery disease, including previous myocardial infarction, angina, percutaneous transluminal coronary angioplasty
  9. History of congestive heart failure
  10. History of liver failure (Child-Pug B or C)
  11. Currently taking a monoamine oxidase inhibitor or other medication with substantial interaction with duloxetine
  12. Antidepressant use within 4 weeks of study start
  13. Treatment with inhibitors of CYP1A2: fluvoxamine, ciprofloxacin or enoxacin
  14. History of uncontrolled hypertension
  15. History of bipolar disorder
  16. History of seizures over 18 years of age, not during chilhood for febrile seizures
  17. Clinical record of acute glaucoma
  18. Treatment with selective serotonin reuptake inhibitors (SSRIs)
  19. Treatment with serotonin and noradrenaline reuptake inhibitors (SNRIs)
  20. Treatment with tricyclic antidepressants
  21. Treatment with triptans
  22. Treatment with antipsychotic drugs
  23. Treatment with dopamine antagonists
  24. Treatment with oral anticoagulant agents
  25. Treatment with St. John's Wort (Hypericum perforatum)
  26. History of Major depression disorder
  27. History of Generalized anxiety disorder

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

  1. Incidence of CSPS (Chronic post-surgical pain) at 4 months

Secondary endpoints 2

  1. Quality of life by means of questionnaire SF-12
  2. Rate of adverse events perioperatively

Investigational products

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

Test 1

Dulotex 30 mg cápsulas duras gastrorresistentes EFG

PRD2422699 · Product

Active substance
Duloxetine
Pharmaceutical form
GASTRO-RESISTANT CAPSULE, HARD
Route of administration
ORAL
Max daily dose
30 mg milligram(s)
Max total dose
30 mg milligram(s)
Max treatment duration
21 Day(s)
Authorisation status
Authorised
ATC code
N06AX21 — -
Marketing authorisation
79575
MA holder
NEURAXPHARM SPAIN, S.L.U.
MA country
Spain
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
Yes
Modification description
repacked for blinding purposes

Placebo 1

Capsules of maltodextrine

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

Parc De Salut Mar

5 Total trials 1 Recruiting 4 Ended
Academic / Non-commercial
Sponsor organisation
Parc De Salut Mar
Address
Passeig Maritim De La Barceloneta 25-29
City
Barcelona
Postcode
08003
Country
Spain

Scientific contact point

Organisation
Parc De Salut Mar
Contact name
Dr. Antonio Montes Pérez

Public contact point

Organisation
Parc De Salut Mar
Contact name
Recerca

Locations

1 EU/EEA country · 13 investigational sites

By country

CountryMS statusPlanned subjectsSites
Spain Ongoing, recruiting 294 13
Rest of world — 0 —

Investigational sites

Spain

13 sites · Ongoing, recruiting
Hospital Universitari Germans Trias I Pujol
Anaesthesiology, Carretera Canyet 1a Planta, 08916, Badalona
Hospital Clinico Universitario De Valladolid
Anaesthesiology, Avenida Ramon Y Cajal 3, 47003, Valladolid
Hospital Lluis Alcanyis De Jativa Valencia
Anaesthesiology, Carretera Xativa Silla 2, 46800, Xativa
Hospital Universitari Vall D Hebron
Anaesthesiology, Edificio Materno-Infantil, Passeig De La Vall D'hebron 119-129, Barcelona
Hospital General Universitario Dr. Balmis
Anaesthesiology, Avinguda Del Pintor Baeza 12, 03010, Alicante
Hospital Universitari Arnau De Vilanova De La Gerencia Territorial De Lleida
Anaesthesiology, Av Alcalde Rovira Roure 80, 25198, Lleida
Hospital Universitario 12 De Octubre
Anaesthesiology, Bloque D, Avenida De Cordoba S/n, Madrid
Son Llatzer Hospital
Anaesthesiology, Carretera Manacor Km 4 Son Ferriol, 07198, Palma De Mallorca
University Hospital Son Espases
Anaesthesiology, Carretera Valldemossa 79, 07120, Palma
Hospital Del Mar
Anaesthesiology and Resucitation, Passeig Maritim De La Barceloneta 25-29, 08003, Barcelona
Bellvitge University Hospital
Anaesthesiology, Carrer De La Feixa Llarga Sn, 08907, L'hospitalet De Llobregat
Consorci Sanitari Del Maresme
Anaesthesiology, Carretera De Cirera 230, 08304, Mataro
Althaia Xarxa Assistencial Universitaria De Manresa Fundacio Privada
Anaesthesiology, Carrer Del Doctor Joan Soler 1-3, 08243, Manresa

Country notifications

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

Country Trial startTrial end Recruitment startRecruitment end Early termination
Spain 2024-06-26 2024-10-03

Results and documents

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

Documents 6 files

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

TypeTitleVersion
Protocol (for publication) D1 Protocol 2023-505860-12-00_Redacted 3.2
Protocol (for publication) D1_Protocol_Justification use IMP off label 1
Recruitment arrangements (for publication) K1_Recruitment arrangements 1
Subject information and informed consent form (for publication) L1_SIS and ICF 1.2
Summary of Product Characteristics (SmPC) (for publication) E1_SmPC Duloxetine 1
Synopsis of the protocol (for publication) D1_Protocol Synopsis 2023-505860-12-00 ES 3.2

Application history

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

#TypeCodeSubmittedReference MSConclusionDecision date
1 INITIAL IN 2023-06-02 Spain Acceptable with conditions
2023-09-15
 2023-09-15
2 SUBSTANTIAL MODIFICATION SM-1 2023-10-06 Spain Acceptable with conditions 2023-11-03
3 SUBSTANTIAL MODIFICATION SM-2 2023-12-03 Spain Acceptable
2024-03-01
 2024-03-01
4 SUBSTANTIAL MODIFICATION SM-5 2024-10-21 Spain Acceptable 2024-11-21
5 SUBSTANTIAL MODIFICATION SM-6 2025-02-19 Spain Acceptable 2025-03-12
6 SUBSTANTIAL MODIFICATION SM-7 2025-03-12 Spain Acceptable
2025-04-25
 2025-04-25
7 SUBSTANTIAL MODIFICATION SM-9 2026-01-26 Spain Acceptable 2026-02-26
8 NON SUBSTANTIAL MODIFICATION NSM-4 2026-03-03 Spain Acceptable 2026-03-03

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