Long-term pain modulation by intravenous esketamine in Complex Regional Pain Syndrome:
a non-inferiority study

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 recognized therapeuticy option in refractory pain
in CRPS, which sometimes in at least a part of the patients has a prolonged
therapeutic effect. Unfortunately, in 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.

This study has been transitioned to CTIS with ID 2024-511877-31-00 check the CTIS register for the current data.

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.

prospective, randomized, non-inferiority study

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 6x 1 day per 2 weeks (in total 3
months)

This study poses a negligible risk. The added risk compared to standard
treatment is the negligible risk of additional vena punctures.
All participants have baseline measurements and receive the esketamine
treatment according to their study arm. At baseline and 3 months after ketamine
treatment, different parameters will be recorded. Pain intensity, quantitative
sensory testing and thermography will be reported and blood samples will be
taken. The standard treatment group comes to the hospital for a 6-day hospital
admission and 2 outpatient visits at the Center for Pain Medicine. The
experimental group has 6 site visits for daycare ketamine infusion and 2
additional outpatient visits at the Center for Pain Medicine. All patients will
be called at home after the esketamine infusion to assess the pain intensity
and possible side effects. Each patient will be enrolled for the duration of 6
months. At the end of study, all participants will continue to receive medical
care for their CRPS . If patients were a responder to esketamine treatment
they can be scheduled for the standard treatment or the experimental treatment
after consulting their pain physician. Patient burden can potentially be
reduced by offering ketamine in a more flexible day-care treatment compared to
a 6-day consecutive hospital admission.