Evaluation of the Efficacy of Intra-nasal Sufentanil for Analgesia of Vaso-occlusive Crisis in Sickle-cell Adults.

NCT ID: NCT04076748

Last Updated: 2023-03-07

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE3
• Total Enrollment: 196 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-07-20
• Study Completion Date: 2024-01-31

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.

Conditions

Sickle Cell Crisis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Experimental

• Intra Nasal Sufentanil (50 µg.ml-1): Load dose : 0.3 µg. kg-1, Followed by bolus : 5 µg / 10 minutes with 2 bolus maximum.

As soon as the venous route and ten minutes after the last administration of sufentanil:

• Morphine IV: 3 mg / 5 minutes.
• Objective: numeric rating scale (NRS) ≤ 3/10.

Group Type: EXPERIMENTAL

Sufentanil

Intervention Type: DRUG

The intervention is intranasal Sufentanil adminstration, then IV morphine as soon as possible.

Control

• EMONO : Given by respiratory administration via a face mask at a rate suitable for patient ventilation (generally at least 9l.min-1), Until a venous route is obtained and without exceeding 30 minutes.

• Morphine IV: Load dose: 0.1mg. kg-1 as soon as possible; Then bolus: 3mg / 5 minutes.

• Objective: NRS ≤ 3/10

Group Type: ACTIVE_COMPARATOR

EMONO

Intervention Type: DRUG

In the control group, patients will receive EMONO then IV morphine as soon as possible.

Interventions

Sufentanil

The intervention is intranasal Sufentanil adminstration, then IV morphine as soon as possible.

Intervention Type: DRUG

EMONO

In the control group, patients will receive EMONO then IV morphine as soon as possible.

Intervention Type: DRUG

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Hospital, Bordeaux

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Eric FRISON, Dr

Role: STUDY_CHAIR

USMR

Locations

Hopital Pellegrin

Bordeaux, , France

Site Status: RECRUITING

Hôpital Louis Mourier

Colombes, , France

Site Status: NOT_YET_RECRUITING

Gonesse Hospital

Gonesse, , France

Site Status: RECRUITING

Hôpital Edouard Herriot

Lyon, , France

Site Status: RECRUITING

Hôpital Charles Nicolle

Rouen, , France

Site Status: NOT_YET_RECRUITING

Hôpital Rangueil

Toulouse, , France

Site Status: RECRUITING

CH de Cayenne

Cayenne, , French Guiana

Site Status: RECRUITING

CHU Pointe à Pitre

Les Abymes, , Guadeloupe

Site Status: NOT_YET_RECRUITING

Countries

France; French Guiana; Guadeloupe

Central Contacts

Michel GALINSKI, Pr

Role: CONTACT

michel.galinski@chu-bordeaux.fr

5 56 79 48 26 ext. +33

Cedric GIL-JARDINE, Dr

Role: CONTACT

cedric.gil-jardine@chu-bordeaux.fr

Facility Contacts

Michel GALINSKI, Pr

Role: primary

michel.galinski@chu-bordeaux.fr

5 56 79 48 26 ext. +33

Nicolas JAVAUD

Role: primary

nicolas.javaud@aphp.fr

Mustapha YOUSSEF

Role: primary

mustapha.youssef@ch-gonesse.fr

Virginie LVOVSCHI

Role: primary

virginie.lvovschi@chu-lyon.fr

Luc-Marie JOLY, Pr

Role: primary

luc-marie.joly@chu-rouen.fr

Annie MOMO BONA

Role: primary

momobona.a@chu-toulouse.fr

Narcisse ELENGA

Role: primary

narcisse.elenga@ch-cayenne.fr

Maryse ETIENNE-JULAN

Role: primary

maryse.etienne-julan@chu-guadeloupe.fr

Other Identifiers

CHUBX 2017/46

Identifier Type: -

Identifier Source: org_study_id