Clinical trial NCT04076748: Evaluation of the Efficacy of Intra-nasal Sufentanil for Analgesia of Vaso-occlusive Crisis in Sickle-cell Adults.
Official title: Evaluation of the Efficacy of Intra-nasal Sufentanil for Analgesia of Vaso-occlusive Crisis in Sickle-cell Adults.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Sickle Cell Crisis
Keywords: analgesia
vaso-occlusive crisis
sufentanil
intra-nasal
Lead sponsor: University Hospital, Bordeaux
Sponsor class: OTHER
First posted: 2019-09-03
Enrollment: 196
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The analgesic treatment for vaso-occlusive crisis (VOC) in sickle-cell patients is an emergency. The reference treatment is morphine, which requires a venous way sometimes difficult to obtain in these patients. Sufentanil intranasal has been shown to be effective in traumatology. The objective is to evaluate, in VOC, the efficacy of intranasal sufentanil relayed by morphine IV compared to the usual protocol, Equimolar Mixture of Oxygen-Nitrous Oxide (EMONO) relayed by morphine intravenous (IV).

Detailed description: Pain of VOC in sickle-cell patients seen in the emergency department (ED) is severe. Analgesia is a therapeutic emergency based on intravenous (IV) morphine titration. However, for technical reasons (patient flow in ED, difficult venous access) this treatment is often delayed. The Equimolar Mixture of Oxygen-Nitrous Oxide (EMONO), an inhaled analgesic administered, makes it possible to temporarily and very partially compensate for the major analgesic defect. Its efficacy in this indication has never been demonstrated; it is less effective than opiates during labour and is associated with a risk of addiction. The intranasal (IN) route is used to administer strong opiates such as sufentanil. Sufentanil IN has been shown to be rapidly effective in traumatology. Its duration of action is similar to that of morphine IV but its duration of action is far too short to completely replace it. Its ideal place would therefore be the initial phase of the management while waiting for a venous approach.

The strategy is to propose an intranasal administration of an opioid (Sufentanil) at the initial management of vaso-occlusive crisis in sickle-cell patients in the ED waiting to a venous route for morphine.

Follow-up of the study will be carried out in the ED with numeric rating scale (NRS) measurement every 5 minutes until patient relief (defined by NRS ≤ 3/10). Once relieved, NRS will be measured every 15 minutes for at least 2 hours. Treatment-related side effects will be systematically investigated up to 4 hours after starting treatment. In particular, the respiratory rate and level of consciousness will be measured, and all side effects will be recorded: nausea, vomiting, dizziness, behavioural disorders, pruritus.

Eligibility criteria: Inclusion Criteria:

* Age 18 to 75 years old;
* Sickle-cell patient.
* Signs of a vaso-occlusive crisis (migratory bone pain, which may occur in the limbs, spine, thorax, pelvis, skull) or crisis known as such by the patient;
* Severe pain (NRS ≥ 6/10) on admission to the ED;
* Registered with the social security scheme or his beneficiaries (except AME)
* Signature of free and informed consen.

Exclusion Criteria:

* Strong opioids received in the previous 6 hours;
* Pregnancy or breastfeeding;
* Woman not menopausal nor sterile without effective contraception (HAS criteria)
* Oxygen saturation below 93%;
* Patients who cannot cooperate because of a State of agitation or a Cognitive impairment
* Unable to communicate;
* Unable to do self-assessment;
* Allergy or intolerance to opiates or nitrous oxide.
* Abuse or addiction to opioids
* Liver insufficiency
* Renal insufficiency
* Severe asthma or chronic obstructive bronchopulmonary disease
* Pulmonary disease necessitating oxygen
* Presence of seriousness signs:

  * All respiratory seriousness signs
  * all neurologic signs or consciousness impairment (coma Glasgow scale under 15)
  * hyperthermia over than 39°C
  * Signs of intolerance of acute anemia
  * Signs of hemodynamic failure
  * Known organ failure (renal insufficiency, pulmonary high blood pressure)
  * A description by the patient of a non usual crisis.
* Current treatment with nasal vasoconstrictors is ongoing
* Head injury with suspicion of high intracranial pressure
* Severe thoracic trauma or decompensated respiratory insufficiency
* Contraindications of intranasal administration:

  * Facial trauma
  * Nose or sinusal surgery in the previous 6 months before inclusion
  * Chronic nose and upper airway alteration (ex. facial malformation)
  * Acute nose and upper airway alteration (ex. Epistaxis, acute respiratory infection, sinusitis).
* Contraindication to nitrous oxide
* Contraindication to morphine
* Patient's refusal to participate in the study.
* Previous inclusion in the study of less than 14 days.

Primary outcomes:
measure: Proportion of patients relieved (NRS ≤ 3/10) 30 minutes after starting treatment in each group.
timeFrame: From date of inclusion to 30 minutes after
Secondary outcomes:
measure: Adverse events occuring until 4 hours after treatment initiation.
timeFrame: From date of inclusion to 4 hours after
measure: Morphine consumption (mg)
timeFrame: from date of inclusion to 60 minutes after
measure: Morphine consumption (mg)
timeFrame: from date of inclusion to 120 minutes after
measure: Time to obtain an effective analgesia
timeFrame: through study completion, an average of 4 hours
measure: Time to obtain a venous access
timeFrame: through study completion, an average of 4 hours
Other outcomes:
Locations:
city: Bordeaux
country: France
facility: Hopital Pellegrin
city: Colombes
country: France
facility: Hôpital Louis Mourier
city: Gonesse
country: France
facility: Gonesse Hospital
city: Lyon
country: France
facility: Hôpital Edouard Herriot
city: Rouen
country: France
facility: Hôpital Charles Nicolle
city: Toulouse
country: France
facility: Hôpital Rangueil
city: Cayenne
country: French Guiana
facility: CH de Cayenne
city: Les Abymes
country: Guadeloupe
facility: CHU Pointe à Pitre
Study officials:
affiliation: USMR
name: Eric FRISON, Dr
role: STUDY_CHAIR
References: