Use of Analgesic Treatment to Reduce Signs of Pain in Patients With Disorders of Consciousness.
Condition: Disorders of Consciousness; Severe Brain Injury; Post-comatose Non-communicative Patients; Vegetative State; Minimally Conscious State
MeSH terms: Brain Injuries; Consciousness Disorders; Persistent Vegetative State
Study type: Interventional
Phase: Phase 1

Summary: 
      The purpose of this study is to characterize and improve pain and nociception management in
      patients with disorders of consciousness (DOC). This project is divided into two phases, a
      first phase to evaluate pain level and a second phase which consist of a clinical trial to
      evalute pain medication efficacy.

      The main aim is to evaluate the use of the Nociception Coma Scale-Revised (NCS-R) and its
      cut-off score (i.e., 5) as an assessment and management tool to define guidelines for
      managing pain in patients with DOC. In this double-blind, placebo-controlled clinical study,
      we will evaluate the use of analgesic treatments in reducing pain in subacute/chronic
      patients. The project will also allow us to validate the NCS-R cut-off score defined
      previously.
    

Detailed description: 
      The study will be performed within one week (i.e, 7 days) and consists of two phases:

        -  Phase 1 "Patients selection (D0)": Patients will be assessed by the NCS-R during
           experimental stimulation (rest, tactile, noxious) and mobilizations (physiotherapy).
           Patients with potential pain will be included in the phase 2.

        -  Phase 2 "Analgesic administration (D1 and D2)": double-blind placebo-controlled
           randomized clinical trial on potential responders identified in phase 1. A medical
           doctor of our team will suggest to the physician in charge to prescribe the dedicated
           medication. One placebo and one real treatment will be administered on day 1 and 2 by
           the nurses at least half-hour before the physiotherapy. Randomization between day 1 and
           2 will be applied at that time.

      For each day of phase 1 and 2, several assessments will be performed: NCS-R, CRS-R and
      spasticity assessment.
    

Intervention name(s): Analgesic administration; Placebo administration
Intervention type(s): Drug; Drug
Intervention description(s): Level 1 : Paracétamol 1g/Acetaminophène 1g, Ibuprofène 600mg, Diclofénac 50mg.
Level 2: Tramadol 50mg.
Level 3: Oxycodone 5mg, Morphine sulfate 10mg.
Increase of a prior level 3 medication :
1/6 of the total dose of daily level 3 medication (e.g. the patient receives 30mg of oxycodone a day. He will be administered a single dose of 5 mg for the study), defined as a breakthrough dose in the management of chronic pain. To standardize the treatment, the dose of the prior level 3 medication will be converted to oxycodone. Several online tools exist to do the conversion between opioids (e.g. mobile app Orthodose ®).
If the oral intake or the gastrostomy use is not possible, the breakthrough dose will be administered by subcutaneous route. The dose will also be 1/6 of the daily dose and will be converted to injectable morphine. Conversion to injectable morphine will be performed with any equivalence tool (such as the mobile app Orthodose ®); Folavit (folic acid, 0.4 mg)
Intervention MeSH terms: Analgesics
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Supportive Care
Keywords: Nociception; Pain; Disorder of Consciousness; Nociception coma scale revised