Intranasal Sufentanil for Analgesia of Severe Sickle Cell Vaso-occlusive Pain Crisis in the Pediatric (INVOPE)

Assistance Publique - Hôpitaux de Paris

Status and phase: Not yet enrolling; Phase 3

Conditions: Vaso-occlusive Crisis

Treatments: Drug: Sufentanil

Study type: Interventional

Funder types: Other

Identifiers

NCT06181695

APHP211035

Details and patient eligibility

About

Sickle cell disease (SCD) is characterized by an abnormal hemoglobin, the main protein in the red blood cell. From the first months of life, acute obstruction of the vessels of the microcirculation manifests as intense and unpredictable recurrent episodes of severe pain. In the Emergency Department (ED), patients presenting with a vaso-occlusive crisis (VOC) required a rapid evaluation and administration of pain relief therapies and hydration.

this strategy is based on an intranasal (IN) administration of Sufentanil at the initial management of children with VOC, followed by morphine intravenous (IV) relay as soon as possible, compared to the usual care procedure with IV morphine as soon as possible.

The hypothesis is that the use of this IN opioid at the beginning of the management of children with VOC can reduce the time before being pain relieved. Indeed, the IN administration make it easier and faster to administer.

Full description

Sufentanil is a powerful opioid analgesic used intravenously by emergency physicians for the sedation of intensive care, intubated and ventilated patients. It is therefore already present in the pharmacopoeia of emergencies. As the duration of action of inztranasal Sufentanil is too short to completely replace the IV morphine, a very promising approach would be to use it during the initial phase of the management of severe pain in children with painful sickle cell crisis while waiting for a venous access.

The INVOPE trial is a phase III trial evaluating the intranasal sufentanil in sickle cell disease children with severe VOC.

The INVOPE trial is a randomized controlled, multicenter, double blind, two parallel-group in a 1:1 ratio, placebo-controlled superiority trial comparing the analgesic efficacy of the sufentanil IN + standard care IV morphine / versus placebo IN + IV morphine as soon as possible.

Children will be randomized in two groups:

• Experimental group: IN Sufentanil procedure with IV administration of morphine as soon as possible
• Control group : IN placebo IN procedure with IV administration of morphine as soon as possible

The objective of this trial is to compare a procedure consisting in IN Sufentanil followed by IV morphine, when compared to IN placebo followed by IV morphine alone, in children with severe vaso-occlusive crisis.

Enrollment: 182 estimated patients

Sex: All

Ages: Under 18 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

At inclusion visit:

• Sickle-cell disease = Hemoglobin SS or SC or Sß-thalassemia
• Age < 18 years old
• Weight > 10 kgs
• Registered with the social security scheme (or State Medical Aid - AME) or his/her beneficiaries
• Informed consent of the holder (s) of the exercise of parental authority
• Age < 18 years old

At randomisation visit

• Presenting to the ED with 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 determined at triage, defined as:

  • EVENDOL ≥ 10/15 in children aged 0-8 years or
  • NRS-11 ≥ 7/10 in children aged 8 years to less than 18 years

• Informed consent of the holder (s) of the exercise of parental authority signed at inclusion visit

Exclusion criteria

• At inclusion visit

  • Known cirrhosis
  • End-stage renal disease requiring kidney dialysis
  • Known hypersensitivity or contraindication to sufentanil or any of the excipients
  • Contraindication to morphine
  • Facial malformation, epistaxis, blocked or traumatised nose
  • Severe asthma
  • Patient's or parent's refusal to participate
  • Participation in another interventional trial
  • Parents who do not speak French

At randomization visit

• Known cirrhosis
• End-stage renal disease requiring kidney dialysis
• Known hypersensitivity or contraindication to sufentanil or any of the excipients
• Contraindication to morphine
• Facial malformation, epistaxis, blocked or traumatised nose
• Severe asthma
• Patient's or Parent's refusal to participate or withdrawal of parental consent
• Participation in another interventional trial
• Patient has already been randomised to the INVOPE trial during a previous VOC
• Strong opioids received <6 hours (morphine, oxycodone, hydromorphone, fentanyl, sufentanil, nalbuphine)
• Respiratory failure (tachypnea; bradypnea; paradoxical breathing; grunting; head-bobbing; nasal flaring; retractions (subcostal, suprasternal, intercostal, sternal))
• Oxygen saturations below 95% on initial assessment
• Pneumonia requiring oxygen therapy
• Hemodynamic disorders: tachycardia, hypotension
• Altered conscious state as defined by a Glasgow Coma score less than 15
• Positive urinary pregnancy test for woman of childbearing potential (postpubertal female with sexual activity)
• Nasal or sinus surgery within 6 months before randomisation
• High fever > 39°C
• Sign of intolerance of acute anaemia
• Description by the patient (or the parents) of the unusual nature of the attack

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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182 participants in 2 patient groups, including a placebo group

Sufentanil IN + Morphine IV

Experimental group

Description:

Intranasal Sufentanil + IV morphine:

Treatment:

Drug: Sufentanil

Placebo IN + Morphine IV

Placebo Comparator group

Description:

Placebo of Sufentanil administered intranasally (IN) . One single administration +IV morphine similar to the experimental arm:

Treatment:

Drug: Sufentanil