A Phase 4 interventional study of Esketamine and Placebo in Endometriosis, sponsored by Region Skane. Not yet recruiting. Open to female participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-10-19.
Sponsored by Region Skane · Phase 4, Interventional, and Treatment
Endometriosis is a chronic condition affecting approximately 10% of women. It is frequently associated with persistent or recurrent pelvic and abdominal pain. The mechanisms underlying pain in endometriosis are complex and may include direct stimulation from endometriotic lesions and local inflammation, nerve involvement, and alterations in central pain processing. In some individuals, sensitization of the nervous system may result in pain persisting despite limited ongoing tissue injury.
Surgery is an important treatment option for patients whose symptoms are insufficiently controlled by medical therapy or in whom surgery is indicated to improve fertility. The primary aim of surgery is to remove endometriosis lesions, thereby reducing symptoms and improving quality of life.
However, patients undergoing surgery for endometriosis often experience more severe postoperative pain and require greater opioid consumption than patients undergoing other gynecological procedures. They may also be at increased risk of developing persistent postoperative pain, defined as pain that continues beyond the expected healing period and persists for months after surgery.
Esketamine is a well-established medication used in anesthesia and pain management. Its pharmacological effects and safety profile are well characterized. It is commonly administered in patients with pre-existing pain conditions or chronic opioid use. Previous studies suggest that esketamine may reduce acute postoperative pain, decrease opioid requirements, and provide benefits in certain neuropathic and chronic pain conditions. However, its efficacy and safety have not been systematically evaluated in patients undergoing surgery for endometriosis.
The ENDPAIN trial aims to evaluate the efficacy and safety of perioperative esketamine in patients undergoing surgery for endometriosis, with the goal of improving postoperative pain management and recovery.
Primary Objective: To evaluate the efficacy and safety of perioperative esketamine in reducing postoperative pain in patients undergoing intra-abdominal surgery for endometriosis.
Secondary Objectives: To collect information on preoperative and postoperative pain in patients undergoing surgery for endometriosis in order to improve understanding of the mechanisms and risk factors associated with severe acute postoperative pain and persistent postoperative pain.
To collect information on the effects of other analgesic medications used as part of routine clinical care in participating centres and to explore potential interactions between these medications and esketamine.
Primary Endpoint: Postoperative pain measured using a Numerical Rating Scale (NRS) at 30 minutes, and at 6, 12, 24, and 48 hours after surgery.
Secondary Endpoints:
Hospital-free days within 30 days after surgery, defined as the number of days spent alive and outside an acute-care hospital during the first 30 postoperative days.
Opioid consumption during the first 48 postoperative hours. Quality of Recovery (QoR-15) score. Serious adverse events. Adverse reactions associated with esketamine, including hypertension, tachycardia, hallucinations or dissociative symptoms, sedation, nausea, and vomiting.
Persistent postoperative pain and other patient-reported outcomes assessed three months after surgery.
Trial Design: The ENDPAIN trial is a triple-blinded, randomized, placebo-controlled clinical trial with a follow-up duration of three months.
Participants will be enrolled on the day of surgery. Most study data will be collected during the first 48 postoperative hours. A follow-up assessment will be conducted three months after surgery and may take place either during a study visit or by telephone, according to participant preference and local site procedures.
Trial Population: Adult patients undergoing elective surgery for endometriosis will be eligible for inclusion.
Patients will be excluded if they:
Do not provide informed consent. Have a known hypersensitivity or allergy to esketamine. Have a current or previous history of ketamine or esketamine misuse. Have a medical condition in which esketamine is contraindicated, such as elevated intracranial or intraocular pressure.
Have severe systemic disease (ASA Physical Status > III). Have severe psychiatric illness. Intervention: Participants will be randomly assigned in a 1:1 ratio to one of two treatment groups. Participants allocated to the intervention group will receive esketamine 0.5 mg/kg following induction of anesthesia, followed by a continuous infusion of 0.15 mg/kg/hour until approximately 20 minutes before skin closure. Participants allocated to the control group will receive an equivalent volume of placebo consisting of sodium chloride solution (saline).
925 studies on the registry are indexed under Endometriosis; 264 are open to participants now.
This study's planned enrollment of 1,000 is above the median of 65 across 539 interventional studies indexed under Endometriosis.
Browse Endometriosis studies →Region Skane is the lead sponsor of 382 studies on the registry; 118 are open to participants now.
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Exclusion Criteria:
They will receive esketamine as an adjunct to the standard postoperative pain therapy
Drug: Esketamine
They will receive placebo (NaCl)
Drug: Placebo
Esketamine iv administered as a 0.5 mg/kg (of adjusted weight) right after anesthesia induction followed by a continuous infusion of esketamine 0.15 mg/kg/h until around 20 minutes before skin closure.
NaCl as a bolus after induction followed by a continuous infusion until 20 minutes before skin closure
Time weighted longitudinal postoperative pain measurement over 48 hours.
A time-weighted longitudinal postoperative pain measurement over 48 hours, measured using the numeric rating scale (NRS, 0-10) for pain at 30 minutes after admission to the PACU, 6, 12, 24 and 48 hours postoperatively during activity (coughing or sitting)
Time frame: From 30 minutes after awakening till 48 hours postoperative
Hospital-free days within 30 days after surgery
Days spent outside of the hospital during the first 30 postoperative days
Time frame: From surgery day until 30 day postoperative
Opioid consumption in the PACU and at 6, 12, 24 and 48 hours after surgery
Opioid consumption in the PACU and at 6, 12, 24 and 48 hours after surgery, measured as a sum of all opioids - intravenously and orally -converted to Oral Morphine Equivalents (OME; mg), administered in the PACU, in the ward, or at home after discharge if this happens before 48 hours after surgery
Time frame: From awakening until 48 hours postoperative
Quality of recovery-15 questionnaire (QoR-15) at 24 hours postoperatively
Quality of recovery-15 questionnaire (QoR-15) at 24 hours postoperatively
Time frame: At 24 hours after surgery
The proportion of participants with one or more serious adverse events within 48 hours
The proportion of participants with one or more serious adverse events (defined according to the International Council for Harmonization good clinical practice guidelines) within 48 hours
Time frame: From drug administration until 48 hours after surgery
The proportion of participants with one or more selected treatment-emergent adverse events within 48 hours postoperatively
The proportion of participants with one of the following treatment-emergent adverse events within 48 hours postoperatively: * Tachycardia, defined as a heart rate \> 120 bpm for more than 15 minutes; * Hypertension, defined as a systolic blood pressure \> 180 mmHg and/or a diastolic blood pressure \> 100 mmHg for more than 15 minutes; * Sedation, defined as a RASS scale score \< -1 * Dissociation/hallucination/dizziness, defined as any reported episode of dissociation or hallucination; * Nausea/vomiting, defined as the administration of any additional antiemetic drug requested by the participant or as any reported episode of nausea and/or vomiting;
Time frame: From drug administration until 48 hours after surgery
No study locations are listed for this record.
Plan to share: No
No publications or documents are linked to this record.
From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗
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Studies of the drug tested here: Esketamine