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Duloxetine to Prevent Chronic Postsurgical Pain After Inguinal Hernia Repair in Patients at High Risk

Phase 3
Active, not recruiting
Conditions
Chronic Post-surgical Pain
Interventions
Drug: Placebo
Registration Number
NCT06606067
Lead Sponsor
Parc de Salut Mar
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.

Recruitment & Eligibility

Status
ACTIVE_NOT_RECRUITING
Sex
Male
Target Recruitment
294
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
DuloxetineDuloxetineParticipants received Duloxetine 30 mg / 24 h 2 weeks before surgery and 1 week after surgery
PlaceboPlaceboParticipants received Placebo / 24 h 2 weeks before surgery and 1 week after surgery
Primary Outcome Measures
NameTimeMethod
Efficacy of duloxetine versus placebo in reducing the incidence of Chronic Post-Surgical Pain (CPSP) at 4 months4 months after surgery

The primary outcome will be a change in the Chronic Post-Surgical Pain (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. Criteria of CPSP: 1) The pain develops after a surgical procedure or increases in intensity after the surgical procedure, 2) the pain should be of at least 3 months' duration and significantly affected the quality of life, 3) the pain is either a continuation of acute post-surgery pain or develops after an asymtomatic period, 4) the pain is either localized to the surgical field, projected to the innervation territory of a nerve situated in the surgical field, or referred to a dermatome, 5) other causes of the pain should be excluded: infection or continuing malignancy in cancer surgery.

Secondary Outcome Measures
NameTimeMethod
Characteristics of Chronic Post-Surgical Pain (CPSP)4 months after surgery

Compare the characteristics of Chronic Post-Surgical Pain (CPSP) in the intervention and control groups with neuropathic pain questionnaire (Douleur Neuropathique 4 (DN4 spanish version).

Intensity of Pain4 months after surgery

Compare the intensity characteristics of Chronic Post-Surgical Pain (CPSP) with Brief Pain Inventory-Short Form (BPI-SF).

Quality of life in patients with Chronic Post-Surgical Pain (CPSP)4 months after surgery

Compare the quality of life in the intervention and control groups with the SF-12 questionnaire (validated Spanish version 2)

Adverse effects of perioperative duloxetine comparing with placebo2 weeks before surgery and 1 week after surgery

Comparing the rates of adverse effects of perioperative duloxetine and placebo for the primary prevention of Chronic Post-Surgical Pain (CPSP).

Trial Locations

Locations (1)

Hospital del Mar

🇪🇸

Barcelona, Spain

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