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

December 12, 2023 updated by: Assistance Publique - Hôpitaux de Paris

Intranasal Sufentanil for Analgesia of Severe Sickle Cell Vaso-occlusive Pain Crisis in the Pediatric Emergency Department: a Double Blind Randomized Versus Placebo Controlled Trial

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.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed 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.

Study Type

Interventional

Enrollment (Estimated)

182

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Sufentanil IN + Morphine IV
Intranasal Sufentanil + IV morphine:
Drug: Sufentanil
Administration of intranasal sufentanil
Other Names:
  • sufentanil IN + morphine IV
Placebo Comparator: Placebo IN + Morphine IV
Placebo of Sufentanil administered intranasally (IN) . One single administration +IV morphine similar to the experimental arm:
Drug: Sufentanil
Administration of intranasal sufentanil
Other Names:
  • sufentanil IN + morphine IV

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Evaluation of the Efficacy of Intra-nasal Sufentanil for Analgesia of Vaso-occlusive Crisis in Sickle-cell in children
Time Frame: at 30 minutes
efficacy of the analgesia at 30 minutes after IN injection, in children with SCD presenting to the pediatric ED with a severe VOC with Pain relief is defined as EVENDOL score ≤ 5/15 or NRS-11 score ≤ 3/10
at 30 minutes

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Proportion of children relieved (EVENDOL ≤ 5/15 or NRS-11 ≤ 3/10) at 10, 20, 40, 50 and 60 minutes after the IN injection inclusion
Time Frame: at 60 minutes
Proportion of children relieved (EVENDOL ≤ 5/15 or NRS-11 ≤ 3/10) at 10, 20, 40, 50 and 60 minutes after the IN injection inclusion
at 60 minutes
Proportion of children with a moderate pain (EVENDOL ≤ 9/15 or NRS-11 ≤ 6/10) at 10, 20, 30, 40, 50 and 60 minutes after the IN injection
Time Frame: EVENDOL ≤ 5/15 or NRS-11 ≤ 3/10 at 10, 20, 40, 50 and 60 minutes
Proportion of children relieved (EVENDOL ≤ 5/15 or NRS-11 ≤ 3/10) at 10, 20, 40, 50 and 60 minutes after the IN spray;
EVENDOL ≤ 5/15 or NRS-11 ≤ 3/10 at 10, 20, 40, 50 and 60 minutes
To demonstrate that {IN Sufentanil +IV morphine(as a standard of care)} procedure, when compared to {IN Placebo + IV morphine (as a standard of care)} procedure, is able to decrease the level of morphine consumption
Time Frame: from randomisation to 60 minutes after
Morphine consumption (mg). Assessed morphine consumption after treatment initiation, until 60 minutes
from randomisation to 60 minutes after
To demonstrate the safety of the {IN Sufentanil +IV morphine} procedure, when compared to {IN Placebo + IV morphine } procedure, that is an absence of increase rate of hemodynamic and non-hemodynamic side effects of opiace
Time Frame: until 4 hours after the IN injection
Rates of hypotension, hypoxia, bradycardia, respiratory distress, headache, nausea, vomiting, sleepiness and itchiness until 4 hours after the IN injection
until 4 hours after the IN injection
To evaluate the safety of all children aged 0-18 years
Time Frame: From randomisaton to 4 hours after
This outcome is defined by the proportion of patients with at least one adverse events during the medical care, until 4 hours after treatment initiatio
From randomisaton to 4 hours after
To demonstrate that the {IN Sufentanil +IV morphine (as a standard of care)} procedure, when compared to {IN Placebo + IV morphine (as a standard of care)} procedure, is able to improve the management of a VOC episode
Time Frame: after 4 hours of randomisation
Rate of admission after the ED visit
after 4 hours of randomisation
To demonstrate that the {IN Sufentanil +IV morphine (as a standard of care)} procedure, when compared to {IN Placebo + IV morphine(as a standard of care)} procedure, is able to decrease the proportion of VOC complications
Time Frame: at hospital discharg, after 4 hours after randomisation
Rate of Acute chest syndrome: at hospital discharge Rate of admission in ICU, invasive ventilation, non-invasive ventilation, oxygene therapy: at hospital discharge Rate of Transfusion: at hospital discharge Rate of death: at hospital discharge
at hospital discharg, after 4 hours after randomisation

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Assistance Publique - Hôpitaux de Paris

Investigators

  • Principal Investigator: Camille AUPIAIS, Pre, Assistance Publique des Hopitaux de Paris

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

May 2, 2024

Primary Completion (Estimated)

May 30, 2026

Study Completion (Estimated)

May 29, 2027

Study Registration Dates

First Submitted

November 15, 2023

First Submitted That Met QC Criteria

December 12, 2023

First Posted (Actual)

December 26, 2023

Study Record Updates

Last Update Posted (Actual)

December 26, 2023

Last Update Submitted That Met QC Criteria

December 12, 2023

Last Verified

December 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • APHP211035

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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