Intranasal Sufentanil for Analgesia of Severe Sickle Cell Vaso-occlusive Pain Crisis in the Pediatric Emergency Department

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Assistance Publique Hopitaux De Paris

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Hemic and Lymphatic Diseases [C15], Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

Trial duration

21 Jul 2025 → ongoing

Decision date (initial)

2023-11-24

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

French Ministry of Health (PHRC N 2020)

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Others, Efficacy

To demonstrate the superiority of a procedure consisting in IN administration of sufentanil followed by IV administration of morphine as soon as possible {IN sufentanil + IV morphine (as a standard of care) }, when compared to placebo and IV administration of morphine as soon as possible {IN Placebo + IV morphine (as a standard of care)}, on the efficacy of the analgesia at 30 minutes, in children with SCD presenting to the pediatric ED with a severe VOC.

Secondary objectives 9

1. a) To demonstrate the superiority of the {IN Sufentanil +IV morphine (as a standard of care)} procedure, when compared to {IN Placebo + IV morphine (as a standard of care)} procedure, on the efficacy of the analgesia at 10, 20, 40, 50 and 60 minutes after the IN spray
2. b) To demonstrate the superiority of the {IN Sufentanil +IV morphine (as a standard of care)} procedure, when compared to {IN Placebo + IV morphine (as a standard of care)} procedure, on the efficacy of the analgesia “moderate” at 10, 20, 30, 40, 50 and 60 minutes after the IN spray
3. c) 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 delay before relief, the delay before administration of others opioid analgesics, and the duration of the ED visit
4. d) 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
5. e) To demonstrate the safety of the {IN Sufentanil +IV morphine(as a standard of care)} procedure, when compared to {IN Placebo + IV morphine (as a standard of care)} procedure, that is an absence of increase rate of hemodynamic and non-hemodynamic side effects of opiates
6. f) To evaluate the safety of all children aged 0-18 years
7. g) 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
8. h) 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
9. i) 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 parent and child satisfaction with the quality of analgesia and management during the emergency room stay

Conditions and MedDRA coding

vaso-occlusive crisis due to sickle cell disease

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 2

1. 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
2. At randomization visit • Age < 18 years old • 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 0-18 years (this pain scale is allowed in children > 8 years only for randomization) 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 or at randomisation visit

Exclusion criteria 2

1. At inclusion visit • Known cirrhosis • End-stage renal disease requiring kidney dialysis • Known hypersensitivity to sufentanil, any of the excipients or to morphine • Facial malformation, epistaxis, blocked or traumatised nose. • Patient's or parent's refusal to participate • Parents who do not speak French
2. At randomization visit • 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 • Hemodynamic disorders: tachycardia, hypotension • Altered conscious state as defined by a Glasgow Coma score less than 15 • Patient's or Parent's refusal to participate or withdrawal of parental consent • Patient has already been randomised to the INVOPE trial during a previous VOC • Positive urinary pregnancy test for woman of childbearing potential (postpubertal female with sexual activity), • Participation in another interventional trial

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Proportion of children relieved at 30 minutes after the IN spray. The pain will be evaluated with : An hetero-evaluation by the EVENDOL Scale for children aged less than 8 years. An auto-evaluation by the Numeric Pain Rating Scale (NRS-11) for children aged 8 years to less than 18 years. Pain relief is defined as EVENDOL score ≤ 5/15 or NRS-11 score ≤ 3/10.

Secondary endpoints 9

1. a) Proportion of children relieved (EVENDOL ≤ 5/15 or NRS-11 ≤ 3/10) at 10, 20, 40, 50 and 60 minutes after the IN spray;
2. b) 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 spray;
3. c) Time from triage to relief (EVENDOL ≤ 5/15 or NRS-11 ≤ 3/10) Time from triage to venous access Time from triage to IV morphine initiation Proportion of children with a first dose of opioids within 30 min of arrival Time from triage to parenteral opioid initiation (IV morphine or IN Sufentanil) Time from triage to admission/discharge decision
4. d) Morphine consumption (mg) 60, 120 and 240 minutes after the IN injection;
5. e) Rates of hypotension, hypoxia, bradycardia, respiratory distress, headache, nausea, vomiting, sleepiness and itchiness until 4 hours after the IN injection;
6. f) All adverse events;
7. g) Rate of admission after the ED visit Length of hospital stay: at hospital discharge;
8. h) 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
9. i) Satisfaction with the quality of analgesia and management during the emergency room stay = For children ≥ 8 years - Global satisfaction with treatment (NRS-11, by children and parent) -Total Quality Pain Management and Desire to receive the same intranasal treatment during a future severe VOC by children and parent o For children < 8 years -Global satisfaction with treatment (NRS-11, by parent) -Total Quality Pain Management and Desire to receive the same intranasal treatmen

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Auxiliary 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Assistance Publique Hopitaux De Paris

Sponsor organisation

Assistance Publique Hopitaux De Paris

Address

Porte 23, 1 Avenue Claude Vellefaux 1 Avenue Claude Vellefaux

City

Paris Cedex 10

Postcode

75475

Country

France

Scientific contact point

Organisation

Assistance Publique Hopitaux De Paris

Contact name

Camille AUPIAIS

Public contact point

Organisation

Assistance Publique Hopitaux De Paris

Contact name

Camille AUPIAIS

Locations

1 EU/EEA country · 25 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 12 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

8 submissions — initial application plus substantial / non-substantial modifications