EndometriosisPhase 4ENDPAINNCT07881562
Perioperative Esketamine Safety and Efficacy in Reducing Postoperative ENDometriosis PAIN (the ENDPAIN Trial): a Randomized Controlled Trial.
A Phase 4 study testing Esketamine in people with Endometriosis, run by Region Skane.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Endometriosis
- What is being tested?
- Esketamine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 1,000 participants
- Where
- No sites listed yet
- Study dates
- 1 Jan 2028to 31 Mar 2031
- Phase
- Phase 4
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- elective intra-abdominal surgery for endometriosis
- age > 18 years.
Who cannot join
- Inability to understand the study information,
- No consent,
- American Society of Anesthesiology (ASA) class > 3,
- Pregnancy or breastfeeding,
- Hemodynamic instability before surgery,
- Current or previous severe psychiatric conditions,
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- Known or suspected allergy or intolerance to esketamine,
- Contraindications for esketamine administration (according to the Summary of product characteristics)
- Current chronic use or abuse of opioids,
- Ongoing therapy/use of esketamine,
- Scheduled for minor procedures (e.g. hysteroscopies and abdominal wall procedures).
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
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.
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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).
- Conditions
- Endometriosis
- Being tested
- Esketamine, Placebo
- Keywords
- Endometriosis, Postoperative pain, Gynecological surgery, Esketamine
- Medical subject headings
- Endometriosis, Pain, Postoperative
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EsketamineDrug
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.
PlaceboDrug
NaCl as a bolus after induction followed by a continuous infusion until 20 minutes before skin closure
| Study group | Role | What they receive |
|---|---|---|
| Intervention group | Experimental | They will receive esketamine as an adjunct to the standard postoperative pain therapy Receives: Drug: Esketamine |
| Control group | Placebo comparator | They will receive placebo (NaCl) Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: From 30 minutes after awakening till 48 hours postoperative
Secondary outcomes (5)
Hospital-free days within 30 days after surgery
Days spent outside of the hospital during the first 30 postoperative days
Measured: 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
Measured: 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
Measured: 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
Measured: 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;
Measured: From drug administration until 48 hours after surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Oct 2026
- Study start1 Jan 2028 (estimated)
- Primary completion31 Dec 2030 (estimated)
- Study completion31 Mar 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for EndometriosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 1,000 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Region Skane
- Sponsor type
- University, hospital or other
- Collaborators
- Sahlgrenska University Hospital, Uppsala University Hospital, Karolinska Institutet and Department of Obstetrics and Gynecology, Södersjukhuset, Stockholm, Sweden., Ullevaal University Hospital, Helsinki University Central Hospital
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07881562
- Sponsor's protocol ID
- 2026-528328-41-00
- Other IDs
- 2026-528328-41-00
- Acronym
- ENDPAIN
- Status last verified
- Oct 2026
- First submitted
- 12 Oct 2026
- Last updated
- 19 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No