Use of Analgesic Treatment to Reduce Signs of Pain in Patients With Disorders of Consciousness.

University of Liege

Status and phase: Completed; Phase 1

Conditions: Vegetative State; Severe Brain Injury; Minimally Conscious State; Post-comatose Non-communicative Patients; Disorders of Consciousness

Treatments: Drug: Placebo administration; Drug: Analgesic administration

Study type: Interventional

Funder types: Other

Identifiers

NCT04330547

2009-241 (Other Identifier)

2019-86

Details and patient eligibility

About

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.

Full 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.

Enrollment: 19 patients

Sex: All

Ages: 16 to 99 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Have had an acquired brain injury with a loss of consciousness > 28 days (patients) or have no history of previous brain injury (healthy controls)
• Legally authorized surrogate available to provide informed consent.
• Diagnosis of vegetative/unresponsive (VS/UWS) or minimally conscious state (MCS) or emergence of the minimally conscious state without communication (eMCS; as defined by the CRS-R, see above).
• Medically stable (i.e., no systemic illness or disease).
• Patients with NCS-R score during mobilization above or equal to the previously determined cut-off score or NCS-R scores during mobilization equivalent to NCS-R score obtain during nociceptive stimulation will be included in the second phase of the study (i.e. D1 and D2).

Exclusion criteria

• History of developmental, neurologic, or major psychiatric disorder resulting in functional disability.
• Contraindication or unwillingness to discontinuing sedating and centrally-active drugs (benzodiazepine, long-acting sedating drugs) within 48 hours of assessment.
• Upper limb contusions, fractures or flaccid paralysis.
• Uncontrolled epilepsy and already on level 1 drugs

Trial design

Primary purpose: Supportive Care

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Quadruple Blind

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19 participants in 2 patient groups, including a placebo group

Analgesic administration

Active Comparator group

Description:

The analgesic treatment will be tailored to the patient's medication and will be based on 3 levels (based on Ventafridda et al., 1985): * Level 1 : Non-opioid analgesics * Level 2 : Weak opioids analgesics * Level 3 : Strong opioids analgesics If the patient is already on pain medications, we will add the lowest effective dose of the level above the level of the regular pain medications of the patient. (e.g. if the patient has no analgesic treatment, he will be given a non-opioid analgesic (level 1). If he already has a level 1 treatment, we will go for level 2 medication. If he has level 2 treatment, we will go for level 3. And if the patient is already at level 3, we will increase the dosage by steps (reference: 5mg oxycodone as first choice for level 3 drugs)). Preferably, the medication will be administered by oral intake or gastrostomy feeding tube. If it is not possible, other routes of administration are allowed.

Treatment:

Drug: Analgesic administration

Placebo administration

Placebo Comparator group

Description:

Folavit capsules will be used as a placebo

Treatment:

Drug: Placebo administration