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

NCT04330547 | Completed Phase 1

• 2 other identifiers: 2019-862009-241
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

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

Keywords

Nociception; Pain; Disorder of Consciousness; Nociception coma scale revised

Outcome Measures

Primary Outcomes (2)

• Nociception Coma Scale-Revised (NCS-R)

  The NCS-R (Chatelle et al., 2012) is used to assess the perception of acute pain in patients with disorders of consciousness. It is composed of 3 subscales (motor, verbal and facial expressions) respectively scoring from 0 (no response) to 3 (highest response level). Here the NCS-R is administered in 4 different conditions: at rest, during tactile stimulation, during experimental nociceptive stimulation (pressure on the bed of the left and right nail) and during mobilization (physiotherapy).

  through study completion, an average of 2 years

• Coma Recovery Scale-Revised (CRS-R)

  The CRS-R (Giacino et al., 2004) is the gold standard for the behavioural assessment of the level of consciousness and is widely used in patients with chronic disorders of consciousness. The CRS-R is composed of six subscales that assess the following domains: visual, motor, auditory and oro-motor/verbal functions, as well as communication, and arousal. The score ranges from 0 to 23, in which the lowest score indicates coma and the highest score indicates the emergence from the minimally conscious state. The diagnosis is made according to the presence\\absence of particular behavioural responses.

  through study completion, an average of 2 years

Secondary Outcomes (1)

• Modified Ashworth Scale (MAS)

  through study completion, an average of 2 years

Study Arms (2)

Analgesic administration

ACTIVE COMPARATOR

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.

Drug: Analgesic administration

Placebo administration

PLACEBO COMPARATOR

Folavit capsules will be used as a placebo

Drug: Placebo administration

Interventions

Analgesic administration DRUG

* 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. 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 ®). 2. 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 ®)

Analgesic administration

Placebo administration DRUG

Folavit (folic acid, 0.4 mg)

Placebo administration

Eligibility Criteria

• Age: 16 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Liege: lead

Study Sites (1)

Centre Hospitalier Universitaire de Liège

Liège, 4000, Belgium

Location

Related Publications (4)

• Ventafridda V, Saita L, Ripamonti C, De Conno F. WHO guidelines for the use of analgesics in cancer pain. Int J Tissue React. 1985;7(1):93-6.

  PMID: 2409039 BACKGROUND

• Giacino JT, Kalmar K, Whyte J. The JFK Coma Recovery Scale-Revised: measurement characteristics and diagnostic utility. Arch Phys Med Rehabil. 2004 Dec;85(12):2020-9. doi: 10.1016/j.apmr.2004.02.033.

  PMID: 15605342 BACKGROUND

• Bohannon RW, Larkin PA, Smith MB, Horton MG. Relationship between static muscle strength deficits and spasticity in stroke patients with hemiparesis. Phys Ther. 1987 Jul;67(7):1068-71. doi: 10.1093/ptj/67.7.1068.

  PMID: 3602099 BACKGROUND

• Chatelle C, Majerus S, Whyte J, Laureys S, Schnakers C. A sensitive scale to assess nociceptive pain in patients with disorders of consciousness. J Neurol Neurosurg Psychiatry. 2012 Dec;83(12):1233-7. doi: 10.1136/jnnp-2012-302987. Epub 2012 Aug 20.

  PMID: 22906615 BACKGROUND

MeSH Terms

Conditions

Consciousness Disorders; Brain Injuries; Persistent Vegetative State; Pain

Condition Hierarchy (Ancestors)

Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Neurocognitive Disorders; Mental Disorders; Brain Diseases; Central Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Wounds and Injuries; Brain Damage, Chronic; Unconsciousness

Study Officials

• Steven Laureys, M.D., P.h.D

  Centre du Cerveau, Coma Science Group (GIGA Consciousness)

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: SUPPORTIVE CARE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: PhD

Study Record Dates

• First Submitted: March 9, 2020
• First Posted: April 1, 2020
• Study Start: February 21, 2018
• Primary Completion: February 19, 2019
• Study Completion: April 28, 2021
• Last Updated: May 3, 2021

Record last verified: 2021-04

Locations

BE (1)