Long-term Pain Modulation by Intravenous Esketamine in CRPS (KetCRPS-2)

Erasmus University

Status: Invitation-only

Conditions: Complex Regional Pain Syndromes; CRPS (Complex Regional Pain Syndromes)

Treatments: Drug: S-ketamine infusion inpatient setting; Drug: S-ketamine infusion outpatient setting

Study type: Interventional

Funder types: Other

Identifiers

NCT05212571

MEC-2021-0426 (Other Identifier)

NL77785.078.21

2021-000640-21 (EudraCT Number)

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 60 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Meeting the new International Association for the Study of Pain (IASP) diagnostic criteria for CRPS ("the Budapest Criteria) (Harden et al., 2010) or having met the new IASP diagnostic criteria of CRPS ("CRPS with Remission of Some features") (Goebel et al., 2021).
• Willing and capable to participate in the study.
• CRPS in one upper extremity and/or CRPS in one lower extremity
• Treatment in an elective setting.
• Adequate comprehension of the Dutch language
• Age ≥ 18 years

Exclusion criteria

• Severe liver disease
• Psychiatric (schizophrenia, psychosis, delirium, manic depression)
• Active substance abuse
• Intoxication with alcohol or other substances
• Poorly controlled hypertension
• Unstable angina
• High-risk coronary vascular disease
• Heart failure
• Elevated intracranial pressure
• Elevated intraocular pressure
• Thyrotoxicosis
• Pregnancy
• Combination with derivates of xanthines (theophylline) or ergometrine

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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60 participants in 2 patient groups

Outpatient

Experimental group

Description:

The experimental intervention group visits the outpatient clinic to receive intravenous esketamine in day-care setting every 2 weeks for 3 months.

Treatment:

Drug: S-ketamine infusion outpatient setting

Inpatient

Active Comparator group

Description:

The standard treatment group receives intravenous esketamine for 6 consecutive days in hospital.

Treatment:

Drug: S-ketamine infusion inpatient setting