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

Study Overview
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Brief Summary
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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)

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

Conditions
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Subarachnoid Hemorrhage, Aneurysmal, Headache

Intervention / Treatment
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* Drug: Pterygopalatine Fossa Nerve Block with Ropivacaine and Dexamethasone
* Procedure: Placebo Pteryogpalatine Fossa Injection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: In order to be eligible to participate in this study, an individual must meet all of the following criteria: Provision of signed and dated informed consent form 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, subarachnoid hemorrhage within 48 hours of ictus hemorrhage Disease-specific inclusion criteria: Aneurysm identified as culprit of SAH modified Fisher grade 1-4 (on admission imaging) Hunt and Hess 1-3 or World Federation of Neurosurgeons grade 1-4 (on admission, 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: Between 4-48 hours from clipping or coiling procedure (whichever applicable) Successful treatment of culprit vascular lesion (i.e., ≥90% obliteration of aneurysm) Requiring a minimum of 15mg OME prn during the 24-hour period immediately prior to enrollment Exclusion Criteria: 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 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, INR > 1.7 requiring use of systemic anticoagulation, ticagrelor or dual antiplatelet therapy 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 initial diagnostic angiography (vasospasm defined as: moderate-to-severe arterial narrowing on digital subtraction angiography not attributable to atherosclerosis, catheter-induced spasm, or vessel hypoplasia, as determined by a neuroradiologist or neurointerventionalist) 118 Standard pain regimen conditions Elevation of hepatic enzymes prohibiting use of scheduled acetaminophen (i.e., AST or ALT > 3x upper limit level) Chronic liver condition with absolute contra-indication for acetaminophen (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 (acetaminophen)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: Sequential Parallel Comparison Design
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Group 1 - Active - Active<br>Subjects randomized to Group 1 will receive an active PPF nerve block in Stage 1 followed by an active PPF nerve block in Stage 2 of the Double-Blinded Trial Phase | Drug: Pterygopalatine Fossa Nerve Block with Ropivacaine and Dexamethasone<br>* Each PPF-active nerve block will consist of 20mg (4ml) ropivacaine plus 4mg (1ml) dexamethasone<br>* Other names: Pterygopalatine Fossa Nerve Block;|
| Other: Group 2 - Placebo - Active<br>Subjects randomized to Group 2 will receive a placebo PPF-injection in Stage 1 followed by an active PPF nerve block in Stage 2 of the Double-Blinded Trial Phase | Drug: Pterygopalatine Fossa Nerve Block with Ropivacaine and Dexamethasone<br>* Each PPF-active nerve block will consist of 20mg (4ml) ropivacaine plus 4mg (1ml) dexamethasone<br>* Other names: Pterygopalatine Fossa Nerve Block;Procedure: Placebo Pteryogpalatine Fossa Injection<br>* Each placebo PPF-injection will consist of 5ml normal saline<br>|
| Placebo Comparator: Group 3 - Placebo - Placebo<br>Subjects randomized to Group 3 will receive a placebo PPF-injection in Stage 1 followed by a placebo PPF-injection in Stage 2 of the Double-Blinded Trial Phase | Procedure: Placebo Pteryogpalatine Fossa Injection<br>* Each placebo PPF-injection will consist of 5ml normal saline<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary Efficacy Endpoint | prn oral morphine equivalent (OME)/day use | within 24 hours after each PPF-injection spanning the 48 hours of double-blinded treatment period | 
| Primary Safety Endpoint | incidence of radiographic vasospasm | at 48 hours from first PPF-injection (end of double-blinded treatment period) | 
| Primary Tolerability Endpoint | rate of acceptance of second PPF-injection | at 24 hours following the first PPF-injection | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pterygopalatine Fossa Nerve Block