BLOCK-SAH - PPF-Block for Post-SAH Headache

Официальное название

Pterygopalatine Fossa (PPF) Block as an Opioid Sparing Treatment for Acute Headache in Spontaneous Subarachnoid Hemorrhage

Обзор

BLOCK-SAH is a phase II, multicenter, randomized, double-blinded, placebo-controlled clinical trial with a sequential parallel comparison design (SPCD) of bilateral pterygopalatine fossa (PPF) injections with 20mg ropivacaine + 4mg dexamethasone (active, PPF-block) compared to saline (placebo) for headache in survivors of aneurysmal subarachnoid hemorrhage (SAH), while monitoring intracranial arterial mean flow velocities with transcranial Doppler (TCD) peri-intervention (intervention = PPF-injections: active or placebo)

Вмешательства

• Препарат Pterygopalatine Fossa Nerve Block with Ropivacaine and Dexamethasone
  Each PPF-active nerve block will consist of 20mg (4ml) ropivacaine plus 4mg (1ml) dexamethasone
• Процедура Placebo Pteryogpalatine Fossa Injection
  Each placebo PPF-injection will consist of 5ml normal saline

Первичные конечные точки

• Primary Efficacy Endpoint [Срок оценки: within 24 hours after each PPF-injection spanning the 48 hours of double-blinded treatment period]
• Primary Safety Endpoint [Срок оценки: at 48 hours from first PPF-injection (end of double-blinded treatment period)]
• Primary Tolerability Endpoint [Срок оценки: at 24 hours following the first PPF-injection]

Критерии участия

In order to be eligible to participate in this study, an individual must meet all of the following criteria:

• Provision of signed and dated ICF by participant or a legally authorized representative (LAR)
• Stated willingness to comply with all study procedures and availability for the duration of the study
• Male or female, aged ≥18 and ≤ 85 years
• Admitted with a primary diagnosis of spontaneous, non-traumatic, SAH within 72 hours of ictus hemorrhage
• Disease-specific inclusion criteria:

• Spontaneous, non-traumatic SAH
• Subarachnoid pattern of hemorrhage warranting diagnostic DSA due to involvement of at least one of the following regions: quadrigeminal plate, prepontine cistern, perimesencephalic cistern, Sylvian fissure, or surrounding Circle of Willis
• Modified Fisher grade 1-4 (on presentation imaging)
• Hunt and Hess 1-3 or World Federation of Neurosurgeons grade 1-4 (on screening, included only if also fulfilling Glasgow Coma Scale verbal subscore ≥4)
• Minimum Glasgow Coma Scale verbal subscore of 4 (on screening)
• Able to verbalize pain scale scores according to 11-point numeric pain scale

In order to be enrolled and undergo randomization in this study, an individual must meet all of the additional criteria:

• Stabilization period criteria:

• A minimum of 4 hours from DSA with clipping or coiling procedure (whenever applicable)
• Successful treatment of culprit vascular lesion (i.e., ≥90% obliteration of aneurysm), when applicable
• Requiring a minimum of 15mg OME prn for headache analgesia during any 24-hour period during eligibility period

Критерии исключения

An individual who meets any of the following criteria will be excluded from participation in this study:

• Premorbid conditions:

• Pre-existing neurologic, psychiatric, or other condition that would confound neurologic assessment or would make difficult/impossible to accurately assess neurologic and/or functional outcome
• Pre-existing diffuse flow-limiting narrowing of arteries in the Circle of Willis, regardless of etiology (e.g., atherosclerosis, vasculitis, Moya-Moya syndrome)
• Prior use of opioid or barbiturate analgesics for at least two-thirds of the days in previous month, regardless of indication
• Diagnosis of substance use disorder in the previous year
• Infected or wounded skin, or a skin lesion at the site of puncture for PPF- injection
• Uncorrected coagulopathy

• Platelet count < 50,000/μL, International Normalized Ratio (INR) > 1.7
• Requiring use of systemic anticoagulation and antiplatelet therapy (except for aspirin monotherapy).
• SAH-specific:

• Head trauma as etiology of SAH
• Infection as cause for aneurysm or SAH (i.e., mycotic aneurysms)
• Inability to successfully treat culprit vascular lesion
• Diffuse vasospasm on pre-enrollment diagnostic CTA or DSA. Vasospasm is defined as moderate-to-severe arterial narrowing on DSA or CTA not attributable to atherosclerosis, catheter-induced spasm, or vessel hypoplasia, as determined by a neuroradiologist or neurointerventionalist
• Standard pain regimen conditions

• Elevation of hepatic enzymes prohibiting use of scheduled APAP (i.e., AST or ALT > 3x upper limit level)
• Chronic liver condition with absolute contra-indication for APAP (even at lower maximum daily doses)
• Participation in a concurrent investigational/interventional study (observational studies allowed)
• Known to be pregnant, or with a positive pregnancy test
• Allergy or intolerance to the medications used in the PPF-block (i.e., ropivacaine, dexamethasone) or standard pain regimen (APAP)
• Vulnerable populations such as prisoners and inmates (abiding GCP per the study IRB)
• Unable to receive first PPF-injection within 96 hours of ictus hemorrhage

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Последовательный дизайн

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

США · 13 центров

• University of Florida — Gainesville
• University of Miami — Miami
• Cleveland Clinic Foundation Martin Health — Stuart
• Emory University — Atlanta
• University of Maryland Baltimore — Baltimore
• Creighton University Medical Center — Omaha
• University of Rochester Medical College — Rochester
• University of North Carolina — Chapel Hill
• … и ещё 5 центров

Публикации

• Busl KM, Smith CR, Troxel AB, Fava M, Illenberger N, Pop R, Yang W, Frota LM, Gao H, Shan G, Hoh BL, Maciel CB; BLOCK-SAH Investigators. Rationale and Design for the BLOCK-SAH Study (Pterygopalatine Fossa Block as an Opioid-Sparing Treatment for Acute Headache in Aneurysmal Subarachnoid Hemorrhage): A Phase II, Multicenter, Randomized, Double-Blinded, Placebo-Controlled Clinical Trial with a Seque PMID 39138719

Идентификаторы

NCT: NCT06008795 · IRB CED000000829 · 1U01NS124613-01A1

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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