Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Complement Inhibition: Attacking the Overshooting Inflammation @Fter Traumatic Brain Injury (CIAO@TBI)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04489160
Recruitment Status : Not yet recruiting
First Posted : July 28, 2020
Last Update Posted : July 28, 2020
Sponsor:
Collaborators:
Netherlands Brain Foundation
Takeda
Information provided by (Responsible Party):
wcpeul, Leiden University Medical Center

Brief Summary:
Severe Traumatic Brain Injury (s-TBI) is a major cause of death and disability across all ages. Besides the primary impact, the pathophysiologic process of major secondary brain damage consists of a neuroinflammation response that critically leads to irreversible brain damage in the first days after the trauma. A key catalyst in this inflammatory process is the complement system. Inhibiting the complement system is therefore considered to be a potentially important new treatment for TBI, as has been shown in animal studies. This trial aims to study the safety and efficacy of C1-inhibitor compared to placebo in TBI patients. By temporarily blocking the complement system we hypothesize limitation of secondary brain injury and more favourable clinical outcome for TBI patients due to a decrease in the posttraumatic neuroinflammatory response.

Condition or disease Intervention/treatment Phase
Traumatic Brain Injury Trauma, Head Drug: C1 Inhibitor, Human Drug: Placebo Phase 2

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 106 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase II Trial on the Safety and Efficacy of C1 Inhibitor for the Acute Management of Severe Traumatic Brain Injury
Estimated Study Start Date : August 2020
Estimated Primary Completion Date : August 2022
Estimated Study Completion Date : December 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: C1-inhibitor
One dose 6000 IU C1-inhibitor intravenously
Drug: C1 Inhibitor, Human
6000 IU C1-INH
Other Name: Cinryze

Placebo Comparator: Placebo
0.9% saline
Drug: Placebo
0.9% saline




Primary Outcome Measures :
  1. Therapy Intensity Level (TIL) Scale [ Time Frame: First four ICU days ]
    TIL differentiated for various treatment modalities aimed at prevention or control of raised Intracranial Pressure (ICP) and/or for CPP management (0 to 38 points)

  2. Glasgow Outcome Scale Extended (GOSE) [ Time Frame: At 6 months after trauma ]
    Functional outcome (minimum score = 1, maximum score = 8)

  3. Complication rate [ Time Frame: Up to 1 year ]
    Adverse and serious adverse events related possibly related to study medication


Secondary Outcome Measures :
  1. Intracranial pressure (ICP) burden [ Time Frame: First four ICU days ]
    Minutes of ICP>20 mm Hg

  2. CT scan midline shift [ Time Frame: Up to 1 year ]
    in mm

  3. Mortality [ Time Frame: Up to 1 year after trauma ]
  4. Glasgow Outcome Scale Extended (GOSE) [ Time Frame: At discharge (an average of 14 days), 3 and 12 months after trauma ]
    Functional outcome (minimum score = 1, maximum score = 8)

  5. QoLiBri [ Time Frame: At 3, 6 and 12 months after trauma ]
    Quality of Life

  6. SF-36 [ Time Frame: At 3, 6 and 12 months after trauma ]
    Health-related quality of life

  7. EQ-5D-5L [ Time Frame: At 6 and 12 months after trauma ]
    Health-related quality of life

  8. ICU length of stay [ Time Frame: Up to 1 year ]
    in days

  9. Ventilator days [ Time Frame: Up to 1 year ]
    in days

  10. Hospital length of stay [ Time Frame: Up to 1 year ]
    in days

  11. Hospital disposition [ Time Frame: Up to 1 year ]
    Discharged to home, rehabilitation or nursery home

  12. UCH-L1 and GFAP biomarkers [ Time Frame: Baseline (Before adminstration of investigational product ) and 6, 12, 24, 48, 72 and 96 hours after adminstration of investigational product ]
  13. Complement activation [ Time Frame: Baseline (Before adminstration of investigational product ) and 6, 12, 24, 48, 72 and 96 hours after adminstration of investigational product ]
    WIESLAB, C3b/C, C4b/C, C5b-9 ELISA assays, CH50/AC50

  14. Coagulation cascade activation [ Time Frame: Baseline (Before adminstration of investigational product ) and 6, 12, 24, 48, 72 and 96 hours after adminstration of investigational product ]
    PT, aPPT, PLT, D-dimer, fibrinogen

  15. Inflammatory markers [ Time Frame: Baseline (Before adminstration of investigational product ) and 6, 12, 24, 48, 72 and 96 hours after adminstration of investigational product ]
    TNF-alpha, intraleukins



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 64 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age at admission ≥ 18 years and < 65 years;
  • Clinical diagnosis of traumatic brain injury with GCS < 13 (with intracranial deviations);
  • Catheter placement for monitoring and management of increased ICP for at least 24 hours;

Exclusion Criteria:

  • A clear, non-traumatic cause of low GCS (e.g. toxic, cardial) on admission;
  • Not expected to survive more than 24 hours after admission;
  • Brain death on arrival in the participating centers;
  • Severe pre-trauma disability, defined as being dependent on other people;
  • Known prior history of sensibility to blood products or Cinryze;
  • Patients with a history of hereditary angioedema;
  • Patients with a history of thrombosis;
  • Pregnant women.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04489160


Contacts
Layout table for location contacts
Contact: Inge van Erp, BSc +31(0)715262109 i.a.m.van_erp@lumc.nl

Sponsors and Collaborators
Leiden University Medical Center
Netherlands Brain Foundation
Takeda
Investigators
Layout table for investigator information
Principal Investigator: Wilco Peul, MD, MPH, PhD, MBa Leiden University Medical Center
Publications:
Layout table for additonal information
Responsible Party: wcpeul, Principal Investigator, Leiden University Medical Center
ClinicalTrials.gov Identifier: NCT04489160    
Other Study ID Numbers: NL7255105823
First Posted: July 28, 2020    Key Record Dates
Last Update Posted: July 28, 2020
Last Verified: July 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Keywords provided by wcpeul, Leiden University Medical Center:
Traumatic Brain Injury
C1-inhibitor
Neuroinflammation
Efficacy
Safety
Additional relevant MeSH terms:
Layout table for MeSH terms
Brain Injuries
Brain Injuries, Traumatic
Craniocerebral Trauma
Wounds and Injuries
Brain Diseases
Trauma, Nervous System
Central Nervous System Diseases
Nervous System Diseases
Complement C1 Inhibitor Protein
Complement Inactivating Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs