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 Sequential Parallel Comparison Design
Authors: Busl Katharina M. , Smith Cameron R. , Troxel Andrea B. , Fava Maurizio , Illenberger Nicholas , Pop Ralisa , Yang Wenqing , Frota Luciola Martins , Gao Hanzhi , Shan Guogen , Hoh Brian L. , Maciel Carolina B. ,   the BLOCK-SAH Investigators, Boulos Alan , Laufer Andras , Argoff Charles E. , Figueroa Christopher , Barnes Erin , Lee James , Sheikh Mahtab , Bughrara Nibras , Varelas Panayiotis , Schaeffer Toni , Spainhour Christine , Sadan Ofer , Samuels Owen , Thomas Tommy T. , Qadri Yawar , Calvillo Eusebia , Suarez Jose Ignacio , Rosenblatt Kate , Le Doshi Tina Tuong-Vi , Patchell Amber , Hendricks Candace , Kramer Christopher , Bojaxhi Elird , Szymkiewicz Ewa , Rabai Ferenc , Peel Jeffrey , Ng Lauren , Gauthier Megan , Anacker Miriam , Nimma Sindhuja , Fox W. Christopher , Freeman William David , Rabinstein Alejandro , Headlee Amy , Neja Bridget , Huebert Carey , Moore Chyann , Schlecht Ethan R. , Sultze Jane , Pingree Matthew , Khan Muhib , Kissoon Narayan , Reuter Peter , Daha Ali , Curtis Anna , Gillespie Devin , Rozansky Gregory , Kirchen Gwynne , Labinski Jacob , LaTourette James , Jasti Jamie , Hernandez-Meier Jennifer , Mattrisch Linda , Dyara Omar , Coppes Oscar Jim Michael , Abdallah Sarah , Endrizzi Sarah , Aufderheide Tom P. , Suric Vladimir , Spontak Elena , Koerner Ines P. , Mauer Kimberly M. , Feller Sarah , Chung Connie , Dalton Kelsey , Brennan Kevin C. , Aitken Kinga , Chauhan Nabeel , Baratta Jaime , Gooch Michael Reid , Herial Nabeel , Jones Nadirah , Jabbour Pascal , Rosenwasser Robert , Tjoumakaris Stavropoula , Gaskins Wendell , Crisologo Adam , Mustafa Ali , Dyer Amanda , Gunnett Amy , Suprun Andrey , Khaliq Anum , Ahmad Bakhtawar , Ihnatsenka Barys , Augustin Beulah , Lucke-Wold Brandon , Crawford Bronson , Robinson Christopher , Pomar-Forero Daniela , Ruiz Federico Jimenez , Comparan Hector David Meza , Luria Isaac , Da Silva Ivan Rocha Ferreira , Bruno John , Wais Joshua , Acosta Juan , Priddy Kevin , Glicksman Laura , Le-Wendling Linda , Jorand-Fletcher Magali , Koch Matthew , Mallard Matthew , Johnson Melissa , Pizzi Michael Anthony , Nelson Nicholas , Chalouhi Nohra El , Nin Olga , Tighe Patrick , Ameli Pouya , Wardhan Richa , Gatica-Moris Sebastián , Haldal Shilpa , Schutte Soleil , Chembrovich Svetlana , Carneiro Thiago Santos , Zasimovich Yury , Heininger Antonia , Houk Clifton , George Derek , Khan Imad , Williams Mark , Bender Matthew , Barrera Pablo Valdes , Soler Steven , Bhalla Tarun , Mattingly Thomas , Hallquist Tilor , Lele Abhijit V. , James Adrienne , Lim Do , Levitt Michael , Curatolo Michele , Wahlster Sarah , DeLuca Angela , Biluck Charlie , Newman Daniia , Roberge John , Miller Joseph , Roberge Justin , Helm Mercedes , Stanley Michael , Belge Zoe , Lin Carissa , Rathmell James P. , Flynn Martina , Edwards Robert Randolph , Montas Yurerkis 
Published: August 2024

Abstract

Background
Acute post-subarachnoid hemorrhage (SAH) headaches are common and severe. Management strategies for post-SAH headaches are limited, with heavy reliance on opioids, and pain control is overall poor. Pterygopalatine fossa (PPF) nerve blocks have shown promising results in treatment of acute headache, including our preliminary and published experience with PPF-blocks for refractory post-SAH headache during hospitalization. The BLOCK-SAH trial was designed to assess the efficacy and safety of bilateral PPF-blocks in awake patients with severe headaches from aneurysmal SAH who require opioids for pain control and are able to verbalize pain scores.

Methods
BLOCK-SAH is a phase II, multicenter, randomized, double-blinded, placebo-controlled clinical trial using the sequential parallel comparison design (SPCD), followed by an open-label phase.

Results
Across 12 sites in the United States, 195 eligible study participants will be randomized into three groups to receive bilateral active or placebo PPF-injections for 2 consecutive days with periprocedural monitoring of intracranial arterial mean flow velocities with transcranial Doppler, according to SPCD (group 1: active block followed by placebo; group 2: placebo followed by active block; group 3: placebo followed by placebo). PPF-injections will be delivered under ultrasound guidance and will comprise 5-mL injectates of 20 mg of ropivacaine plus 4 mg of dexamethasone (active PPF-block) or saline solution (placebo PPF-injection).

Conclusions
The trial has a primary efficacy end point (oral morphine equivalent/day use within 24 h after each PPF-injection), a primary safety end point (incidence of radiographic vasospasm at 48 h from first PPF-injection), and a primary tolerability end point (rate of acceptance of second PPF-injection following the first PPF-injection). BLOCK-SAH will inform the design of a phase III trial to establish the efficacy of PPF-block, accounting for different headache phenotypes.