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. 2025 Feb;42(1):290-300.
doi: 10.1007/s12028-024-02078-z. Epub 2024 Aug 13.

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

Katharina M Busl  1   2 , Cameron R Smith  3 , Andrea B Troxel  4 , Maurizio Fava  5 , Nicholas Illenberger  4 , Ralisa Pop  6 , Wenqing Yang  4 , Luciola Martins Frota  6 , Hanzhi Gao  7 , Guogen Shan  7 , Brian L Hoh  8 , Carolina B Maciel  6   8 ; BLOCK-SAH Investigators
Collaborators, Affiliations

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

Katharina M Busl et al. Neurocrit Care. 2025 Feb.

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.

Trial registration: ClinicalTrials.gov NCT06008795.

Keywords: Headache; Intensive care; Nerve block; Opioid analgesics; Subarachnoid hemorrhage.

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Conflict of interest statement

Conflict of interest: CBM has received honoraria by the American Academy of Neurology for speaking and writing. KMB has received compensation as an associate editor for Critical Care Medicine and reports honoraria by the American Academy of Neurology for speaking and course directorship. Ethical Approval/Informed Consent: This protocol has been approved by the central institutional review board (Advarra) for this trial, and by the trial’s Data Safety and Monitoring Board. Trial Registration: ClinicalTrials.gov, NCT06008795. Registered 18 August 2023, https://clinicaltrials.gov/study/NCT06008795 .

Figures

Fig. 1
Fig. 1
Study timeline depicting the participant-facing events of BLOCK-SAH. ICU intensive care unit, TCD transcranial Doppler
Fig. 2
Fig. 2
Study design: Sequential Parallel Comparison Design. PPF: pterygopalatine fossa
Fig. 3
Fig. 3
Intervention: pterygopalatine fossa- (PPF-) injection. Steps 1–9 outline how the intervention is performed on each side. Step 4 A: ultrasound image depicting the posterior orbital rim. Step 4 B: ultrasound image depicting the superior edge of the zygomatic arch. Step 5: ultrasound image depicting the space between maxilla and coronoid process of the mandible. Step 8 D: ultrasound image depicting the needle tip located in the PPF. Step 9: ultrasound clip/image depicting injectate spread in the PPF
See this image and copyright information in PMC

References

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