The goal of this randomized controlled trial is to investigate the effect of esketamine versus placebo on the NRS score for chronic pelvic pain. Secondary endpoints are to assess pain scores, side-effects, quality of life, depressive symptoms and pain coping.
Endometriosis is a chronic inflammatory disease affecting approximately 10% of reproductive-aged women. Severe pain symptoms and subfertility result in a lower quality of life, higher prevalence of depression and loss of productivity. Consequently, the economic impact of endometriosis is high. Treatment options to suppress chronic pain symptoms in patients with (deep) endometriosis are inadequate, resulting in increased opioid consumption. Ketamine (in our study we will use the S-enantiomer, esketamine), is a versatile drug with analgesic, anti-inflammatory and antidepressant effects and is commonly used in the treatment of chronic pain patients and has shown promising outcomes. However, whilst esketamine targets multiple aspects of endometriosis simultaneously (pain, inflammation, depression), studies on esketamine as treatment for chronic pain due to endometriosis have never been reported. Therefore we aim to conduct a randomized controlled trial to assess the efficacy of esketamine infusion versus placebo in the treatment of chronic endometriosis-induced pain.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
56
Esketamine dosing regimen is set at 0.1 mg/kg/h as starting dosage. Dosage will be gradually increased based on heart rate, oxygen saturation, blood pressure and side effects (e.g. nausea and dissociative effects) during a period of 8 hours to a maximum of 0.5 mg/kg/h (in steps of 0.1-0.3-0.5 mg/kg/hour). This dosage regimen is similar to that used earlier by Sigtermans et al. \[1\].
8 hour infusion with saline (NaCl 0.9%)
Nederlandse Endometriose Kliniek, Reinier de Graaf Gasthuis
Delft, Netherlands
RECRUITINGChronic pelvic pain
The effect of treatment allocation on the NRS score for chronic pelvic pain. The NRS scale ranges from 0 (no pain) to 10 (worst pain imaginable).
Time frame: 4 weeks after the 8 hour infusion treatment.
Dysmenorrhea
NRS score for dysmenorrhea. The NRS scale ranges from 0 (no pain) to 10 (worst pain imaginable).
Time frame: Baseline and week 4, 8, 12 after the 8 hour infusion treatment
Dyschezia
NRS scores for dyschezia.The NRS scale ranges from 0 (no pain) to 10 (worst pain imaginable).
Time frame: Baseline and week 4, 8, 12 after the 8 hour infusion treatment
Dysuria
NRS scores for dysuria. The NRS scale ranges from 0 (no pain) to 10 (worst pain imaginable).
Time frame: Baseline and week 4, 8, 12 after the 8 hour infusion treatment
Dyspareunia
NRS score for dyspareunia. The NRS scale ranges from 0 (no pain) to 10 (worst pain imaginable).
Time frame: Baseline and week 4, 8, 12 after the 8 hour infusion treatment
Chronic pelvic pain
NRS score for chronic pelvic pain. The NRS scale ranges from 0 (no pain) to 10 (worst pain imaginable).
Time frame: Baseline and week 4, 8, 12 after the 8 hour infusion treatment
Depressive symptoms
Hospital Anxiety and Depression scale, 14 questions, scale from 0-3, higher scores mean worse outcome.
Time frame: Baseline, 4 weeks after infusion treatment
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Endometriosis associated Quality of Life
Endometriosis Health Profile-30 (EHP-30). The overall EHP-30 score ranges from 0 to 100, with a high score indicating poorer health-related quality of life.
Time frame: Baseline and week 4, 8, 12 after the 8 hour infusion treatment
Quality of life in general
EuroQql five-dimensional 5 levels (EQ-5D-5L). According to the Dutch scoring algorithm, the EQ-5D-5L score index value ranges from -0.446 (55555 worst health state) to 1 (11111, best health state).
Time frame: Baseline and week 4, 8, 12 after the 8 hour infusion treatment
Quality of life in general
EuroQql Visual Analog Scale (EQ-VAS). Overall health will be represented by the EQ-VAS, ranging from 0 to 100, with higher scores indicating better health.
Time frame: Baseline and week 4, 8, 12 after the 8 hour infusion treatment
Productivity costs
Adjusted productivity costs questionnaire (iPCQ): institute for Medical Technology Assessment (iMTA). Adjusted medical consumption questionnaire: iMTA. Productivity costs will be measured by calculating absence from paid work (absenteeism), reduced productivity at paid work (presenteeism), and productivity loss in unpaid work. Hours of productivity loss will be translated by a standard cost price of productivity per hour.
Time frame: 12 weeks post-infusion treatment
Medical costs
Medical consumption costs will be calculated based upon the iMCQ.
Time frame: Baseline, 12 weeks post-infusion treatment
Pain coping and cognition
Pain Coping and Cognition list (PCCL), consists of 42 items divided in four scales: pain catastrophising (higher scores mean a higher degree of catastrophising), pain coping (lower scores mean a lower degree of pain coping), internal pain control (lower scores mean less internal pain control) and external pain control (higher scores mean less external pain control.
Time frame: Baseline, 12 weeks post-infusion treatment
The effect infusion treatment psychedelic effects
Bowdle questionnaire, scale from 0-100, higher scores mean worse outcome.
Time frame: On the day of infusion (prior to infusion and during infusion)
Treatment experience
1 question, treatment rating on a scale from 0 (worst experience possible) -10 (excellent experience)
Time frame: Directly after infusion