Long-term Pain Modulation by Intravenous Esketamine in CRPS

NCT ID: NCT05212571

Last Updated: 2023-09-11

Basic Information

• Recruitment Status: ENROLLING_BY_INVITATION
• Clinical Phase: NA
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-04-19
• Study Completion Date: 2027-10-01

Brief Summary

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.

Detailed 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.

Conditions

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Outpatient

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

Group Type: EXPERIMENTAL

S-ketamine infusion outpatient setting

Intervention Type: DRUG

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.

Inpatient

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

Group Type: ACTIVE_COMPARATOR

S-ketamine infusion inpatient setting

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

S-ketamine infusion outpatient setting

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.

Intervention Type: DRUG

Other Intervention Names

ketamine; esketamine; ketamine; esketamine

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Erasmus Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Thomas J. P. Mangnus, MD

Medical doctor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Frank JP Huygen, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Erasmus MC, Center for Pain Medicine

Thomas Mangnus, MD

Role: STUDY_DIRECTOR

Erasmus MC, Center for Pain Medicine

Locations

Erasmus MC

Rotterdam, South Holland, Netherlands

Countries

Netherlands

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Other Identifiers

2021-000640-21

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

MEC-2021-0426

Identifier Type: OTHER

Identifier Source: secondary_id

NL77785.078.21

Identifier Type: -

Identifier Source: org_study_id