Improving Neurotrauma by Depolarization Inhibition With Combination Therapy (INDICT)

NCT05337618 | Recruiting Phase 2

• 1 other identifier: Not yet assigned
• Study Type: interventional
• Target: 72
• Locations: 1 country
• Sites: 1

Brief Summary

This study is a randomized Phase 2 trial to determine the feasibility of real-time electrocorticographic monitoring of spreading depolarizations (SD) to guide implementation of a tier-based protocol of intensive care therapies, aimed at SD suppression, for the management of patients who have undergone acute operative treatment of severe traumatic brain injury.

Conditions

Traumatic Brain Injury

Outcome Measures

Primary Outcomes (1)

• Burden of spreading depolarizations

  Spreading depolarization events will be scored based on review of electrocorticographic recordings. The number of depolarizations per recording day over the period of monitoring will serve as the measure of total burden. The burdens computed for patients will be compared between the two randomization arms.

  During the period of intensive care invasive monitoring, up to two weeks after injury

Secondary Outcomes (4)

• Burden of elevated intracranial pressure

  During the period of intensive care invasive monitoring, up to two weeks after injury

• Burden of cerebral hypoxia

  During the period of intensive care invasive monitoring, up to two weeks after injury

• Burden of low cerebral perfusion

  During the period of intensive care invasive monitoring, up to two weeks after injury

• Glasgow Outcome Score-Extended

  6 months post-injury

Study Arms (2)

SD-Guided Care

EXPERIMENTAL

In this arm, ECoG data will be reviewed for SDs in real-time using the bedside clinical CNS monitor. As a secondary measure, recognition of SDs will be facilitated by custom software on a laptop that receives data from the CNS monitor. Data on SD occurrence will be used to guide treatment in a tier-based therapeutic escalation and de-escalation protocol with the goal of SD suppression. Therapies to be used among the tiers include adjusted targets for MAP, CPP, PaCO2, plasma glucose, temperature, as well as ketamine pharmacotherapy. Changes between tiers are determined by the success or failure of SD suppression at the given treatment level.

Diagnostic Test: Full-band Electrocorticography; Combination Product: Treatment Algorithm

Standard ICU Care

NO INTERVENTION

Management in the Standard ICU Care arm will follow published national guidelines consisting of common ICU-based targets for physiologic intervention that are thought to mitigate the development of secondary brain injuries. Continuous ECoG monitoring will be performed for seizure monitoring, but information on the course of SDs in these patients will not be used to guide care. To enforce blinding to SD-related ECoG data, the ECoG bedside software will be locked with password protection to prevent displays with frequency filtering and time/amplitude scales that are necessary to identify SDs.

Interventions

Full-band Electrocorticography DIAGNOSTIC_TEST

Diagnosis of spreading depolarizations in continuous electrocorticography

SD-Guided Care

Treatment Algorithm COMBINATION_PRODUCT

Protocol for escalation and de-escalation of physiologic-targeted and pharmacologic therapies to treat and prevent spreading depolarizations

SD-Guided Care

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• (1) clinical indication for emergency craniotomy with dural opening to treat acute TBI within 72 hr post-trauma

You may not qualify if:

• persistent bilateral non-reactive pupils or other evidence of non-survivable injury,
• decompressive craniectomy to treat refractory ICP subsequent to diffuse injury, (3) co-enrollment in another therapeutic TBI trial, and
• (4) pregnancy

Sponsors & Collaborators

• University of Cincinnati: lead
• University of New Mexico: collaborator
• University of Pennsylvania: collaborator

Study Sites (1)

University of Cincinnati

Cincinnati, Ohio, 45267, United States

RECRUITING

MeSH Terms

Conditions

Brain Injuries, Traumatic

Condition Hierarchy (Ancestors)

Brain Injuries; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Wounds and Injuries

Central Study Contacts

Jed A Hartings, PhD

CONTACT

513-295-2370; jed.hartings@uc.edu

Karmen Herzig

CONTACT

513-558-0440; herzigkm@ucmail.uc.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: Participants will be randomized to one of two study groups based on a block design with randomized block sizes of 2, 4 or 6 determined individually for each study site.

Study Record Dates

• First Submitted: April 5, 2022
• First Posted: April 20, 2022
• Study Start: December 16, 2022
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): March 20, 2027
• Last Updated: December 22, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will share

Locations

US (1)