Clinical trial NCT06606067: Duloxetine to Prevent Chronic Postsurgical Pain After Inguinal Hernia Repair in Patients at High Risk
Official title: Efficacy of Perioperative Duloxetine in Patients at High Risk for Developing Chronic Postsurgical Pain After Inguinal Hernia Repair: a Multicenter Randomized Controlled Trial.
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Chronic Post-surgical Pain
Keywords: Chronic post-surgical pain
Duloxetine
Prevention
Hernia repair
Lead sponsor: Parc de Salut Mar
Sponsor class: OTHER
Collaborators: name: Carlos III Health Institute
First posted: 2024-09-20
Enrollment: 294
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Duloxetine Placebo
Primary purpose: PREVENTION

Brief summary: The clinical trial will be conducted in 14 Spanish hospitals. It is estimated, based on our previous studies, that 2855 patients scheduled for elective inguinal hernia surgery will have to be assessed to detect patients with ≥ 27% level of risk for Chronic Post-Surgical Pain (CPSP). These high-risk patients will be randomized to 2 treatment groups: one will receive duloxetine for 2 weeks prior to surgery and 1 week after surgery (intervention group) and the other the placebo (control group) during the same periods. The primary outcome will be a ≥ 50% decrease in the CPSP incidence in the intervention group compared to the placebo group, 4 months after surgery.

Detailed description: Prospective, multicenter, double-blind randomized double-blind controlled trial. In the first phase the investigators use the Chronic Post-Surgical Pain (CPSP) risk model to select patients scheduled for inguinal hernia repair with a ≥27% level of risk for CPSP.

A total of 2855 patients will be screened in 14 Spanish hospitals (Hospital del Mar (Barcelona) / Hospital Germans Trias i Pujol (Badalona) / H Vall d'Hebrón (Barcelona) / Hospital de Bellvitge (Barcelona) / Hospital de Cruces (Bilbao) / Hospital 12 de Octubre (Madrid) / Hospital de Valme (Sevilla) / Hospital de Son Espases (Palma de Mallorca) / Hospital Son Llatzer (Palma de Mallorca) / Hospital General de Valladolid (Valladolid)/ Hospital General de Alicante (Alicante)/ Hospital Lluís Alcanyís de Xativa).

The high-risk patients will be randomized to 2 treatment groups to receive 30 mg/d of duloxetine for 2 weeks prior to surgery and 1 week after surgery (intervention group) or placebo (control group) during the same periods.

The primary outcome will be a decrease in the CPSP incidence at 4 months in the intervention group compared to the placebo group with an odds ratio of 0.44 as the effect size. The investigators estimate that it will be necessary to treat 294 participants (147 in each group). Participants that might have CPSP will be detected in follow-up telephone interviews approximately 3 months after surgery. Participants who report pain at that time will be scheduled for an appointment at their hospital's pain clinic to confirm the CPSP diagnosis by exhaustive physical examination and to assess pain intensity, characteristics, and degree of interference with daily living.

Eligibility criteria: Inclusion Criteria:

* Men resident in Spain who are scheduled for open inguinal hernia repair (inpatient or outpatient procedures).
* Risk of post-surgical pain chronification \> 27% using the GENDOLCAT risk scale.

Exclusion Criteria:

* Age under 18 years
* Patients who in the recruiter's opinion have insufficient knowledge of Spanish to understand the trial
* Patients who are currently being treated with duloxetine
* Patents with known allergy to duloxetine
* Serious renal failure (creatinine clearance \>30 ml/min)
* Patients requiring reoperation because of surgical complications
* Transplanted patients
* History of coronary artery disease, including previous myocardial infarction, angina, percutaneous transluminal coronary angioplasty
* History of congestive heart failure
* Currently taking a monoamine oxidase inhibitor or other medication with substantial interaction with duloxetine
* Antidepressant use within 4 weeks of study start
* Treatment with inhibitors of cytochrome P450 mixed-function oxidase system (CYP1A2): fluvoxamine, ciprofloxacin or enoxacin
* Uncontrolled hypertension
* Bipolar disorder
* History of seizures
* Elevated intraocular pressure or risk of acute glaucoma
* Treatment with selective serotonin reuptake inhibitors (SSRIs)
* Treatment with serotonin and noradrenaline reuptake inhibitors (SNRIs)
* Treatment with tricyclic antidepressants
* Treatment with triptans
* Treatment with antipsychotic drugs
* Treatment with dopamine antagonists
* Treatment with oral anticoagulant agents
* Treatment with Hypericum perforatum
* Major depression disorder

Primary outcomes:
measure: Efficacy of duloxetine versus placebo in reducing the incidence of Chronic Post-Surgical Pain (CPSP) at 4 months
timeFrame: 4 months after surgery
Secondary outcomes:
measure: Characteristics of Chronic Post-Surgical Pain (CPSP)
timeFrame: 4 months after surgery
measure: Intensity of Pain
timeFrame: 4 months after surgery
measure: Quality of life in patients with Chronic Post-Surgical Pain (CPSP)
timeFrame: 4 months after surgery
measure: Adverse effects of perioperative duloxetine comparing with placebo
timeFrame: 2 weeks before surgery and 1 week after surgery
Other outcomes:
Locations:
city: Barcelona
country: Spain
facility: Hospital del Mar
Study officials:
affiliation: Hospital del Mar Research Institute
name: Antonio Montes, PhD
role: PRINCIPAL_INVESTIGATOR
References: