Brain Autoregulation Research Study

A Pilot Study to Assess the Feasibility and Safety of Targeting Mean Arterial Pressure to Reduce Intra-operative Hypotension

Randomized, multi-site, study assessing the feasibility of lower limit of autoregulation targeted mean arterial pressure (MAP) vs. standard MAP management in neonates undergoing cardiac surgery with cardiopulmonary bypass. After eligibility screening and consent, subjects will be randomized to either the intervention (study) or control group.

Study Overview

• Status: Withdrawn
• Conditions: Hypotension During Surgery; Hypotension Postprocedural
• Intervention / Treatment: Device: Surgery with Active MAP Management; Other: Surgery without Active MAP Management

Detailed Description

Congenital heart disease (CHD) is the most common birth defect.1 Surgery to treat CHD is complicated by white matter injury (WMI) on brain magnetic resonance imaging (MRI) and neurodevelopmental (ND) deficits in 50% to 75% of neonates after CHD surgery.2-6 Cerebral hypoperfusion is a major mechanism of brain injury during both cardiopulmonary bypass (CPB) and the perioperative period in the intensive care unit (ICU).7-10 Investigators lack diagnostic and therapeutic means to reduce cerebral hypoperfusion-associated white matter injury (WMI) and improve long-term ND outcomes.11 Our long-term goal is to use real-time measurement of the cerebral lower limit of autoregulation (LLA) to manage arterial blood pressure, reduce cerebral hypoperfusion-associated brain injury, and improve long-term ND outcomes in children at risk for brain hypoperfusion. In a prospective, single blind, randomized clinical trial (RCT) in adults undergoing cardiac surgery, investigators previously showed that targeted LLA arterial blood pressure management to maintain mean arterial pressure (MAP) above the LLA decreased the incidence of postoperative delirium by 45%.12 Our preliminary data indicate that neonates are exposed to significantly more cerebral hypotension than adult patients undergoing CPB. Our central hypothesis is that a strategy of targeting mean arterial pressure (MAP) to a level above an individual's LLA will reduce the risk for WMI and neurodevelopmental impairment in neonates undergoing congenital heart surgery. Our team has validated methodology to delineate the LLA and demonstrated the important role of cerebral autoregulation monitoring on short-term outcomes in CHD subjects who have undergone CPB.13 We can rigorously measure cerebral autoregulation in real time and the amount of cerebral hypotension (duration and magnitude) through the integration of near infrared spectroscopy (NIRS) and the arterial blood pressure.14,15 The efficacy of an LLA targeted MAP strategy to minimize WMI and improve ND outcomes can only be demonstrated by a prospective, single-blind, multi-center randomized RCT. To obtain funding for this large multi-center RCT will require the demonstration of feasibility and safety, as well as, an estimation of the sample size needed to show efficacy.

• Study Type: Interventional
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • The Cleveland Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• All neonates (<30 days of age)
• Undergoing cardiothoracic surgery with cardiopulmonary bypass

Exclusion Criteria:

• Less than full term (<37 weeks gestation)
• Weight < 2.50kg
• Genetic abnormality or syndrome except heterotaxy syndrome
• Major non-cardiac anomalies (e.g. congenital diaphragmatic hernia, - omphalocele, holoprosencephaly, anencephaly)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention (Study) Group; Neonates undergoing cardiothoracic surgery (CT) utilizing cardiopulmonary bypass (CPB) who will have active management of their mean arterial pressure (MAP) to keep the MAP above the LLA as measured by a novel autoregulation monitoring modality.	Device: Surgery with Active MAP Management; Neonates undergoing cardiothoracic surgery (CT) utilizing cardiopulmonary bypass (CPB) who will have active management of their mean arterial pressure (MAP) to keep the MAP above the LLA as measured by a novel autoregulation monitoring modality.
Sham Comparator: Control Group; Neonates undergoing cardiothoracic surgery (CT) utilizing cardiopulmonary bypass (CPB) who will have management of their MAP by institutional practice without guidance from an autoregulation monitoring modality.	Other: Surgery without Active MAP Management; Neonates undergoing cardiothoracic surgery (CT) utilizing cardiopulmonary bypass (CPB) who will have management of their MAP by institutional practice without guidance from an autoregulation monitoring modality.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Aim 1: Hypotension Exposure	Primary outcome is to reduce hypotension exposure, defined as the product of duration and magnitude of arterial blood pressure below LLA measured in the operating room and for the first 72 hours in the ICU.	From beginning of surgery until 72 hours post-surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Aim 2: Lower Limit Autoregulation Monitoring (LLA)	To determine LLA targeted MAP vs standard MAP management in real time will not increase perioperative mortality and morbidity in neonates undergoing cardiac surgery with CPB	First 30 days post-surgery in the ICU

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Aim 3: Mean Arterial Pressure Management	Compare LLA targeted MAP vs standard of care MAP management in reducing white matter injury and seizure occurrence and improve neurodevelopment outcomes.	Seizure assessment by EEG first 48 hours post-op, White matter injury assessment by Brain MRI 7-21 days post-op, neurodevelopmental outcome (neurobehavioral assessment at 30 days or at discharge by the NBO, Bayley-4 at 6 and 12 months).

Collaborators and Investigators

• Sponsor: Jennie E Minnich
• Investigators: Principal Investigator: Bradley Marino, MD, MPP, MSSCE, MBA, The Cleveland Clinic

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2028

Study Registration Dates

• First Submitted: October 25, 2025
• First Submitted That Met QC Criteria: October 25, 2025
• First Posted (Actual): October 28, 2025

Study Record Updates

• Last Update Posted (Actual): July 15, 2026
• Last Update Submitted That Met QC Criteria: July 14, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Keywords: neonates; hypotension; cardiothoracic surgery with cardiopulmonary bypass
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Hypotension; Surgical Procedures, Operative
• Other Study ID Numbers: IRB 22-1348

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes