Maximal Medical Treatment of Intracerebral Haemorrhage Pilot Trial - MAX-ICH Pilot Trial (MAX-ICH)

The MAX-ICH pilot trial is a phase-II study aimed at assessing the feasibility and safety of a comprehensive care bundle for patients with intracerebral hemorrhage (ICH). This "maximal medical treatment" approach combines advanced interventions like intensive blood pressure control, rapid anticoagulation reversal, and tranexamic acid administration to potentially improve outcomes. The primary objective is to evaluate recruitment feasibility over 12 months, while secondary objectives include protocol adherence, safety monitoring, and the exploration of clinical outcomes. The study focuses on the critical first 72 hours of care to determine if this approach can be effectively implemented in clinical practice.

Study Overview

• Status: Not yet recruiting
• Conditions: Intra Cerebral Hemorrhage
• Intervention / Treatment: Other: Standard of care; Other: MAX-ICH care bundle

Detailed Description

The MAX-ICH pilot trial is a monocentric, phase-II study designed to evaluate the feasibility and safety of a "maximal medical treatment" care bundle for patients suffering from intracerebral hemorrhage (ICH). ICH is a condition with a notably high rate of mortality and morbidity, and this trial aims to improve outcomes for these patients by utilizing a comprehensive approach to their treatment. Previous clinical trials concentrated on single interventions, such as blood pressure control and the administration of tranexamic acid (TXA) therapy. While these interventions did not achieve their primary efficacy outcomes, they did demonstrate beneficial effects on secondary measures like reducing hematoma expansion and early mortality. The current study builds on this prior research by integrating advanced interventions into a unified and comprehensive care bundle, termed MAX-ICH, with the goal of potentially enhancing patient outcomes.

The primary objective of the trial is to demonstrate the feasibility of recruiting patients within a 12-month period. In addition to this, secondary objectives include assessing the technical feasibility of protocol adherence, targeting a compliance rate of at least 70%. The study will also monitor safety by tracking major adverse cardiovascular events (MACE) and explore a range of clinical outcomes, treatment metrics, and differences between the experimental group receiving the MAX-ICH care bundle and those receiving standard care.

The MAX-ICH care bundle consists of several key components designed to deliver intensive and timely care. Patients will receive 72 hours of treatment in a high-dependency unit, ensuring continuous monitoring and rapid responses to any changes in their condition. Intensive blood pressure control will be implemented through intra-arterial monitoring to maintain stability. If a patient is on anticoagulant therapy, the care bundle mandates rapid reversal of anticoagulation within 60 minutes of presentation. Similarly, tranexamic acid will be administered within 60 minutes, helping to mitigate further hemorrhage. Neurosurgical evaluation will also be conducted within 60 minutes to determine if surgical intervention is warranted. Additionally, counseling will be provided to avoid placing Do-Not-Resuscitate (DNR) orders during the critical first 72 hours, allowing time for the intensive interventions to take effect.

Ultimately, this study aims to determine whether the MAX-ICH care bundle can be feasibly implemented in clinical practice and whether its structured, intensive approach within the first 72 hours of care can lead to improved outcomes for patients with ICH.

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: David J Seiffge, Prof. Dr. med.; Phone Number: +41 31 66 40 509; Email: david.seiffge@insel.ch
• Study Contact Backup: Name: Bernhard M Siepen, Dr. med.; Phone Number: +41 31 63 24 220; Email: bernhard.siepen@insel.ch

Study Locations

• Switzerland
  • Bern, Switzerland, 3010
    • Inselspital, University Hospital Bern
    • Contact: David J Seiffge, Prof. Dr. med.; Phone Number: +41 31 664 05 09; Email: david.seiffge@insel.ch
    • Contact: Bernhard M Siepen, Dr. med.; Phone Number: +41 31 632 89 61; Email: bernhard.siepen@insel.ch

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Symptomatic imaging proven diagnosis of non-traumatic ICH
• Vascular imaging (MR-/CT-angiogram or DSA) on admission to rule out high suspicion of macrovascular bleeding source
• Enrolment no later than 6 hours of symptom onset
• Age >18 years, no upper age limit
• Informed consent as documented by signature or fulfilling the criteria for emergency consent/ deferral consent

Exclusion Criteria:

• Palliative care/comfort therapy decision in the emergency department
• ICH due to trauma (major head trauma <24 hours of symptom onset causing loss of consciousness and thought to be sufficient to have caused the intracerebral bleeding)
• High suspicion of ICH due to arteriovenous malformation (AVM), aneurysm or sinus-venous-thrombosis confirmed by neuroimaging, brain tumor, vasculitis, RCVS/PRES or system disease (liver disease, inherit coagulopathy)
• Severe ICH (haematoma volume >60ml or GCS <8)
• Haematoma evacuation or decompressive craniectomy within 72 hours planned or highly likely (isolated EVD is not an exclusion criterion)
• Severe pre-morbid disability [modified Rankin scale (mRS) is ≥4]
• Contraindication against the use of tranexamic acid
• Active participation in another drug or devices trial concurrently
• Female patient that are either pregnant or breastfeeding
• Contraindications against Clevidipine (allergy to soja, lipid metabolism defect or known severe aortic stenosis)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Control arm (usual care); Control group is treated according to local standard of care	Other: Standard of care; The control group will be treated according to the hospital's standard protocol for patients with spontaneous intracerebral hemorrhage, based on the guidelines of the European Stroke Organisation (ESO). The ESO develops evidence-based recommendations for the optimal care of stroke patients. The recommended immediate measures include: immediate stabilization and assessment, blood pressure control and reduction, brain imaging, surgical intervention for large hemorrhages, coagulation control, and monitoring of intracranial pressure. The specific application of these measures varies depending on the hospital and the treating physicians.
Experimental: Experimental arm (MAX-ICH care bundle); Experimental group is treated according MAX-ICH care bundle	Other: MAX-ICH care bundle; The MAX-ICH care bundle is a comprehensive treatment approach for intracerebral hemorrhage (ICH). Patients receive 72 hours of care in a high-dependency unit like an ICU or hyperacute stroke unit. Intensive blood pressure control is used if systolic blood pressure exceeds 140mmHg, with rapid reduction to below 140mmHg within 60 minutes, and maintenance at or above 110mmHg for at least 75% of the time, with variability kept under 20%. The protocol includes rapid reversal of anticoagulation within 60 minutes, administration of tranexamic acid (1g bolus within 60 minutes, followed by 1g over 8 hours), and neurosurgical evaluation within 60 minutes. Additionally, family counseling is provided to avoid Do-Not-Resuscitate orders during the first 72 hours.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recruitment	Recruitment rate at 12 months	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Technical feasibility	≥70% compliance with MAX-ICH care bundle at 72 hours (experimental group only). Full compliance is defined as all 6 criteria of the MAX-ICH care bundle (for details see study intervention) are fulfilled. After the 12 months recruitment period the percentage of patients for which full compliance at 72h afer randomization to the care bundle group was achieved will be determined.	12 months
Major Adverse Cardiovascular Events	MACE within the first 30 days (i.e. Death, acute coronary syndrome (ACS) or myocardial infarction (MI), deep vein thrombosis (DVT), Pulmonary embolism (PE), VTE (combined DVT/PE), Ischaemic stroke)	30 days
Radiological outcomes	Haematoma expansion at 24 hours	24 hours
Radiological outcomes	Presence and number of new lesions on DWI at 72 hours	72 hours
Radiological outcomes	Absolute and relative PHE volume on FLAIR at 72 hours	72 hours
Clinical outcomes	Mortality at 24 hours	24 hours
Clinical Outcome	Early functional outcome (Modified Rankin Scale (mRS 0-6, no symptoms - death)) at 24 hours	24 hours
Clinical Outcome	Early functional outcome (National Institutes of Health Stroke Scale (NIHSS 0-42, no symptoms - severe stroke)) at 24 hours	24 hours
Clinical outcomes	Mortality at 72 hours	72 hours
Clinical Outcome	Functional outcome (Modified Rankin Scale (mRS 0-6, no symptoms - death)) at 72 hours	72 hours
Clinical Outcome	Functional outcome National Institutes of Health Stroke Scale (NIHSS 0-42, no symptoms - severe stroke)) at 72 hours	72 hours
Clinical outcomes	Mortality at 3 months	3 months
Clinical Outcome	Functional outcome (Modified Rankin Scale (mRS 0-6, no symptoms - death)) at 3 months	3 months
Clinical outcomes	Mortality at 6 months	6 months
Clinical Outcome	Functional outcome (Modified Rankin Scale (mRS 0-6, no symptoms - death)) at 6 months	6 months
Quality of blood pressure control	Rapidity (<60minutes from randomization to reach target blood pressure level)	60 min
Quality of blood pressure control	Sustainability (≥70% of time within target blood pressure level during treatment)	72 hours
Quality of blood pressure control	Variability (<20% variability of blood pressure level during treatment)	72 hours
Quality of blood pressure control	Hypotensive episodes (time below lower threshold)	72 hours
Between group differences	Treatment delivery (% of patients receiving treatment)	72 hours
Between group differences	Metrics (time to treatment, time to target)	72 hours

Collaborators and Investigators

• Sponsor: Insel Gruppe AG, University Hospital Bern
• Investigators: Principal Investigator: David J Seiffge, Prof. Dr. med., Department for Neurology, Inselspital, University Hospital Bern

Study record dates

Study Major Dates

• Study Start (Estimated): December 1, 2024
• Primary Completion (Estimated): May 1, 2026
• Study Completion (Estimated): May 1, 2026

Study Registration Dates

• First Submitted: August 20, 2024
• First Submitted That Met QC Criteria: October 16, 2024
• First Posted (Actual): October 18, 2024

Study Record Updates

• Last Update Posted (Actual): October 18, 2024
• Last Update Submitted That Met QC Criteria: October 16, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Intracranial Hemorrhages; Hemorrhage; Cerebral Hemorrhage
• Other Study ID Numbers: MAX-ICH pilot trial

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Not shared

Drug and device information, study documents

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