An interventional study of S-ketamine infusion inpatient setting and S-ketamine infusion outpatient setting in Complex Regional Pain Syndromes and CRPS (Complex Regional Pain Syndromes), sponsored by Erasmus Medical Center. Completed at 1 site in Netherlands. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-11-13.
Sponsored by Erasmus Medical Center · Not applicable, Interventional, and Treatment
Help build ClinicalTrials.gg — short surveys, remote interviews or testing, in your language. Take part →
Intravenous administration of esketamine is an effective recognized therapeutic option in refractory pain in CRPS, which sometimes in at least a part of the patients has a prolonged therapeutic effect. Unfortunately, CRPS literature contains a wide range of ketamine dosing regimens with the result that clinical protocols on dosage and administration are very heterogeneous. The current esketamine regimen in Erasmus MC consists of a 6-day hospital admission for continuous administration. In the Netherlands, both inpatient and outpatient esketamine treatments are offered. Inpatient and outpatient ketamine treatments have never been compared in randomized controlled trials and it is therefore unknown whether these two dosing regimens are equally effective.
The primary objective is to demonstrate non-inferiority of experimental esketamine administration of 6x 1 day per 2 weeks (in total 3 months) as compared with standard esketamine administration of 1x 6 consecutive days. The end of study is at 6 months after the start of the study/treatment.
Rationale: Complex regional pain syndrome (CRPS) is a debilitating chronic pain condition of one or more limbs. Its diagnosis is based on (combinations of) underlying pathophysiological mechanisms. Achieving relevant pain relief fails in a significant proportion of CRPS patients. Intravenous administration of esketamine is an effective therapeutic option in refractory pain in CRPS, which in at least a part of the patients has a prolonged therapeutic effect. Unfortunately, CRPS literature contains a wide range of ketamine dosing regimens with the result that clinical protocols on dosage and administration are very heterogeneous. In the Netherlands, both inpatient and outpatient esketamine treatments are offered. The current esketamine regimen in Erasmus MC consists of a 6-day hospital admission for continuous administration; however, logistical boundaries limit this therapy. Esketamine infusions in an outpatient setting might increase flexibility and availability of esketamine treatment. However, inpatient and outpatient ketamine treatments have never been compared in randomized controlled trials and it is therefore unknown whether these two dosing regimens are equally effective.
Objective: The primary objective is to demonstrate non-inferiority of experimental esketamine administration of 6x 1 day per 2 weeks (in total 3 months) as compared with standard esketamine administration of 1x 6 consecutive days at 3 months after the start of the study/treatment. The secondary objective is to assess pain scores till 6 months follow-up, logistical problems, adverse effects, questionnaires, thermography and quantitative sensory testing in both treatment groups.
Study design: Prospective, randomized, non-inferiority study in 60 patients
Study population: Sixty adult patients with chronic pain due to CRPS
Intervention: All patients will receive intravenous esketamine. The standard treatment group receives intravenous esketamine for 6 consecutive days (in hospital). The experimental intervention group visits the outpatient clinic to receive intravenous esketamine in day-care setting every 2 weeks for 3 months.
Main study parameters/endpoints: The main study parameter is pain intensity, measured by means of Numerical Rating Scale (NRS), to demonstrate non-inferiority of the experimental treatment after three months.
206 studies on the registry are indexed under Complex Regional Pain Syndromes; 54 are open to participants now.
This study's enrollment of 60 is above the median of 40 across 152 interventional studies indexed under Complex Regional Pain Syndromes.
Browse Complex Regional Pain Syndromes studies →Erasmus Medical Center is the lead sponsor of 478 studies on the registry; 182 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
The experimental intervention group visits the outpatient clinic to receive intravenous esketamine in day-care setting every 2 weeks for 3 months.
Drug: S-ketamine infusion outpatient setting
The standard treatment group receives intravenous esketamine for 6 consecutive days in hospital.
Drug: S-ketamine infusion inpatient setting
S-ketamine is administered intravenously for six consecutive days. The administered dose of S-ketamine is 50 mcg/kg/h and can be increased to a maximum of 200 mcg/kg/h.
Also known as: ketamine, esketamine
S-ketamine is administered intravenously for six hours. The administered dose of S-ketamine is 50 mcg/kg/h and can be increased to a maximum of 200 mcg/kg/h.
Also known as: ketamine, esketamine
Change from baseline pain scores
Pain intensity measured by Numerical Rating Scale (NRS). Minimum value=0 and maximum value is 10. Higher scores mean a worse outcome.
Time frame: Baseline (week 0), During inpatient or outpatient esketamine infusion (week 1 for inpatient protocol / week 1, 3, 5, 7, 9, 11 for outpatient protocol), During telephone consultation (week 1, 3, 5, 7, 9, 11), Follow-up (3 months), End of study (6 months)
Change from baseline Quantitative Sensory Testing
To assess the sensory-discriminative dimensions of pain before and after ketamine treatment
Time frame: Baseline (week 0) and follow-up visit (week 12)
Change from baseline Thermography
Objectively measured effects on the extremity temperature by each of the administration regimens on symptoms vasomotor disturbances. The investigators use an infrared camera.
Time frame: Baseline (week 0) and follow-up visit (week 12)
Adverse events due to S-ketamine infusion
Assessed by physical examination and vital parameters (blood pressure, heart rate, saturation and temperature)
Time frame: During inpatient or outpatient esketamine infusion (week 1 for inpatient protocol / week 1, 3, 5, 7, 9, 11 for outpatient protocol), During telephone consultation (week 1, 3, 5, 7, 9, 11)
Change from baseline pain medication dose
Time frame: Baseline (week 0), follow-up visit (3 months) and end of study (6 months)
Change from baseline Complex Regional Pain Syndrome severity score
according to Harden et al. (2010). All symptoms and signs are scored as Yes = 1 and No = 0. Sum up the total score (i.e., number of "Yes" responses) to derive the total CSS score. The Complex Severity Score can range from 0-16. Higher scores mean a worse outcome.
Time frame: Baseline (week 0) and follow-up visit (3 months)
Global Perceived Effect
The Global Perceived Effect asks the patient to rate, on a numerical scale 0-7, how much their condition has improved or deteriorated since some predefined time point. Higher scores mean a worse outcome. According to Hudak et al. 2000.
Time frame: During telephone consultation (week 1, 3, 5, 7, 9, 11), follow-up visit (3 months) and end of study (6 months)
Patient-Reported Outcomes Measurement Information System (PROMIS) -29 Profile
Assesses 7 domains, each with 4 questions (ranging from 1-5, ranging from no/never/not at all to yes/always/continuously): depression, anxiety, physical function, pain interference, fatigue, sleep disturbance, and ability to participate in social roles and activities. According to Terwee et al. 2014
Time frame: Baseline (week 0) and follow-up visit (3 months)
Short-form McGill Pain Questionnaire-2
Neuropathic pain items capturing the quality of pain. Scale ranging from 0-10. Higher scores mean a worse outcome. According to Dworkin et al., 2009
Time frame: Baseline (week 0) and follow-up visit (3 months)
Pain Catastrophizing Scale
The respondent considers how confident they are performing each activity, while taking their pain into account. Scale from 0-4. Higher scores mean a worse outcome. According to Sullivan et al., 2011
Time frame: Baseline (week 0) and follow-up visit (3 months)
EQ-5D-5L.
To measure health state, comprising mobility, self-care, usual activities, pain/discomfort, anxiety/depression. The 5 questions about health status are scored on a 5-point scale (1-5) Placing these numbers one after the other creates a 5-digit index that represents a health profile (eg 12323). According to Herdman et al., 2011
Time frame: Baseline (week 0) and follow-up visit (3 months)
Pain Self-Efficacy Questionnaire
The respondent considers how confident they are performing each activity, while taking their pain into account. The scale ranges from 0-6. Higher scores mean a better outcome. According to Nicholas et al., 2007
Time frame: Baseline (week 0) and follow-up visit (3 months)
Plan to share: Undecided
Ran from Apr 2022 to primary completion in Aug 2026, 52 months.
Of 64 non-industry interventional studies with no phase under Complex Regional Pain Syndromes, half reached primary completion within 24 months of starting (the median), counting those still running; a quarter within 14 and three quarters within 60. This study's 52 months is above that.
Counting every sponsor, half of 65 studies reached it within 24 months; a quarter within 14 and three quarters within 60.
Since we started tracking on Sep 25, 2026, the dates moved once, on Nov 13, 2026: primary completion Oct 2026 → Aug 2026 and completion Oct 2027 → Aug 2026.
Earlier changes are on the record history on ClinicalTrials.gov ↗
How these figures are worked out, and which studies are left out of them.
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 ↗
This study is completed, as verified in Nov 2026. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
Studies of the drug tested here: Ketamine
Complex Regional Pain Syndromes →