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

Официальное название

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

Обзор

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.

Подробное описание

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.

Вмешательства

• Препарат Sufentanil
  Administration of intranasal sufentanil

Первичные конечные точки

• Evaluation of the Efficacy of Intra-nasal Sufentanil for Analgesia of Vaso-occlusive Crisis in Sickle-cell in children [Срок оценки: at 30 minutes]

Вторичные конечные точки (7)

• 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 [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: until 4 hours after the IN injection]
• To evaluate the safety of all children aged 0-18 years [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: at hospital discharg, after 4 hours after randomisation]

Критерии участия

Критерии включения

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

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Двойное слепое

Основная цель

Лечение

Центры проведения

Список центров уточняется — проверьте первичный протокол.

Публикации

• Prise en charge de la drépanocytose chez l'enfant et l'adolescent. Haute Autorité de Santé. Accessed March 3, 2021. https://www.has-sante.fr/jcms/c_272479/fr/prise-en-charge-de-la-drepanocytose-chez-l-enfant-et-l-adolescent
• Yawn BP, Buchanan GR, Afenyi-Annan AN, Ballas SK, Hassell KL, James AH, Jordan L, Lanzkron SM, Lottenberg R, Savage WJ, Tanabe PJ, Ware RE, Murad MH, Goldsmith JC, Ortiz E, Fulwood R, Horton A, John-Sowah J. Management of sickle cell disease: summary of the 2014 evidence-based report by expert panel members. JAMA. 2014 Sep 10;312(10):1033-48. doi: 10.1001/jama.2014.10517. PMID 25203083
• Gonzalez ER, Bahal N, Hansen LA, Ware D, Bull DS, Ornato JP, Lehman ME. Intermittent injection vs patient-controlled analgesia for sickle cell crisis pain. Comparison in patients in the emergency department. Arch Intern Med. 1991 Jul;151(7):1373-8. PMID 2064488
• Dampier CD, Smith WR, Wager CG, Kim HY, Bell MC, Miller ST, Weiner DL, Minniti CP, Krishnamurti L, Ataga KI, Eckman JR, Hsu LL, McClish D, McKinlay SM, Molokie R, Osunkwo I, Smith-Whitley K, Telen MJ; Sickle Cell Disease Clinical Research Network (SCDCRN). IMPROVE trial: a randomized controlled trial of patient-controlled analgesia for sickle cell painful episodes: rationale, design challenges, in PMID 23539110
• Treadwell MJ, Bell M, Leibovich SA, Barreda F, Marsh A, Gildengorin G, Morris CR. A Quality Improvement Initiative to Improve Emergency Department Care for Pediatric Patients with Sickle Cell Disease. J Clin Outcomes Manag. 2014 Feb;21(2):62-70. PMID 26412961
• Shenoi R, Ma L, Syblik D, Yusuf S. Emergency department crowding and analgesic delay in pediatric sickle cell pain crises. Pediatr Emerg Care. 2011 Oct;27(10):911-7. doi: 10.1097/PEC.0b013e3182302871. PMID 21960091
• Kavanagh PL, Sprinz PG, Wolfgang TL, Killius K, Champigny M, Sobota A, Dorfman D, Barry K, Miner R, Moses JM. Improving the Management of Vaso-Occlusive Episodes in the Pediatric Emergency Department. Pediatrics. 2015 Oct;136(4):e1016-25. doi: 10.1542/peds.2014-3470. Epub 2015 Sep 21. PMID 26391933
• Brandow AM, Nimmer M, Simmons T, Charles Casper T, Cook LJ, Chumpitazi CE, Paul Scott J, Panepinto JA, Brousseau DC. Impact of emergency department care on outcomes of acute pain events in children with sickle cell disease. Am J Hematol. 2016 Dec;91(12):1175-1180. doi: 10.1002/ajh.24534. Epub 2016 Sep 3. PMID 27517842

Идентификаторы

NCT: NCT06181695 · APHP211035

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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