Phase I clinical trial for the feasibility and safety of remote ischemic conditioning for aneurysmal subarachnoid hemorrhage

Abstract

Background: Remote ischemic conditioning (RIC) is a powerful endogenous mechanism whereby a sublethal ischemic stimulus confers a protective benefit against a subsequent severe ischemic insult. RIC has significant potential clinical implications for the prevention of delayed ischemic neurological deficit after aneurysmal subarachnoid hemorrhage (aSAH). Although RIC has been extensively investigated in animal models, it has not been fully evaluated in humans.

Objective: To assess the feasibility and safety of RIC for aSAH in a phase I clinical trial.

Methods: Consecutive patients hospitalized for treatment of an aSAH who met the inclusion/exclusion criteria were approached for consent. Enrolled patients received up to 4 RIC sessions on nonconsecutive days. Primary end points were the development of a symptomatic deep venous thrombosis, bruising, or injury to the limb and request to stop by the patient or surrogate. The secondary end points were the development of new neurological deficits or cerebral infarct, demonstrated by brain imaging after enrollment, and neurological deficit and condition at follow-up.

Results: Twenty patients were enrolled and underwent 76 RIC sessions, 75 of which were completed successfully. One session was discontinued when the patient became confused. No patient developed a deep venous thrombosis or injury to the preconditioned limb. No patient developed delayed ischemic neurological deficit during enrollment. At follow-up, median modified Rankin Scale score was 1 and Glasgow Outcome Scale score was 5.

Conclusion: The RIC procedure was well tolerated and did not cause any injury. RIC for aSAH warrants investigation in a subsequent pivotal clinical trial.

Figures

Figure 1

The distribution across deflation and inflation for each vital sign and physiologic signal monitored. Black box plots show the median, 25th and 75th percentiles, range, and outliers ‘+’. Overlaid in gray is the mean value.

Figure 2

The distribution across timepoints during the RIC sessions for vital signs. Black box plots show the median, 25th and 75th percentiles, range, and outliers ‘+’. Overlaid in gray is the mean value.

Figure 3

The distribution across timepoints during the RIC sessions for other physiologic monitoring measurements (intracranial pressure, central venous pressure, bilateral cerebral blood flow velocities and pulsatility indicies). Black box plots show the median, 25th and 75th percentiles, range, and outliers ‘+’. Overlaid in gray is the mean value.