Chronic Subdural Hematoma
Conditions
Keywords
Chronic Subdural Hematoma, MMA Embolization
Brief summary
This is a prospective, multi-center, open-label, randomized controlled study in which subjects can receive standard of care (SOC) alone or SOC and TRUFILL n-BCA MMA embolization for the treatment of chronic subdural hematomas (cSDH).
Detailed description
This is a prospective, multi-center, open-label, randomized controlled study in which up to 376 subjects will be randomized to receive standard of care (SOC) alone or SOC and TRUFILL n-BCA MMA embolization for the treatment of cSDH.
Interventions
DEVICEExperimental: Interventional Cohort: TRUFILL n-Butyl Cyanoacrylate (n-BCA) Liquid Embolic System
Standard of Care Surgery + Embolization
Standard of Care Surgery Only
DEVICEExperimental: Interventional Cohort: TRUFILL n-BCA Liquid Embolic System
Standard of Care Medical Management + Embolization
Standard of Care Medical Management Only
Sponsors
Cerenovus, Part of DePuy Synthes Products, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 90 Years
Healthy volunteers
No
Inclusion criteria
* Pre-randomization mRS \</= 3 * Confirmed diagnosis of chronic subdural hematoma * Completed informed consent
Exclusion criteria
* Acute subdural hematoma * Prior treatment of target subdural hematoma * Markwalder assessment \>/= 3 * Glasgow Coma Scale \< 9 * Presumed microbial superinfection * CT or MRI evidence of intracranial tumor or mass lesion * Life expectancy \< 1 year * Women who are pregnant, lactating, or who are of childbearing age and plan on becoming pregnant during the study * Current involvement in another clinical trial that may confound study endpoints
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Residual or Re-accumulation of the Chronic Subdural Hematoma (cSDH) (Greater Than [>] 10 Millimeter [mm]) as Assessed by an Independent Core Laboratory OR Any Re-operation or Surgical Procedure on the cSDH at 6 Months | At 6 months | Percentage of participants and odds ratio (OR) of participants with residual or re-accumulation of the cSDH (\>10 mm) at 6 months as assessed by an independent core laboratory or re-operation or surgical procedure on the cSDH at 6 months post-randomization in the treatment with eMMA vs. standard of care is represented. Residual or re-accumulation of the cSDH \>10 mm was a threshold included in the guidelines for surgical evacuation and was considered to be of prognostic importance given its association with mortality, decreased quality of life, and complications from new or repeat procedures. |
| Percentage of Participants With All Adverse Events (AEs) | From randomization up to 6 months | An AE was any untoward medical experience (sign, symptom, illness, abnormal laboratory value, or other medical event) occurring to a participant during the course of the study whether or not related to the investigational device. SAE was any AE that results in: death, persistent or significant disability/incapacity, requires inpatient hospitalization or prolongation of existing hospitalization, was life-threatening experience, a congenital anomaly/birth defect and may jeopardize participant and/or may require medical or surgical intervention to prevent one of the outcomes listed above. All AEs including both serious and non serious were reported. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Good Functional Outcome at 3 Months (Modified Rankin Score [mRS] 0-2 or no Worsening From Baseline if Baseline mRS Greater Than Equal to [>=] 3) | At Month 3 | Participants were considered to have a good functional outcome if the 3-month mRS was less than or equal to (\<=) 2 or otherwise no worsening from baseline mRS if the baseline mRS was \>=3. mRS was used to assess the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability. The scales ranges from 0-6, as follows: 0 = No symptoms; 1 = No significant disability. Able to carry out all usual activities, despite some symptoms; 2 = Slight disability. Able to look after own affairs without assistance, but unable to carry out all previous activities; 3 = Moderate disability. Requires some help, but able to walk unassisted; 4 = Moderately severe disability. Unable to attend to own bodily needs without assistance, and unable to walk unassisted; 5 = Severe disability. Requires constant nursing care and attention, bedridden, incontinent; 6 = Dead; higher values reflecting more severe disability or death. |
| Change From Baseline in Hematoma Volume at 3, 6 and 12 Months, as Assessed by an Independent Core Laboratory | Baseline, Months 3, 6 and 12 | Hematoma volume was assessed by independent core laboratory. An independent imaging core laboratory was utilized to provide an unbiased and standardized assessment of study imaging. Hematoma volume was calculated using the ABC/2 method (multiplying Diameters A, B, and C and dividing by 2), where Diameter A was defined as the largest length in the axial plane to each corner of the SDH, Diameter B was defined as the maximum with 90 degree to Diameter A in the same slice, Diameter C was defined as the maximum height of the hematoma. For the calculation of the height, the number of slices with visible hematoma was multiplied by the thickness of the CT-scan. Change from baseline was defined as: post-baseline value minus baseline value, with negative values indicating improvement with respect to baseline (a reduction in hematoma volume). Baseline was defined as the last non-missing measurement collected prior to randomization. |
| Number of Participants With Greater Than (>) 50 Percent (%) Reduction in Hematoma Volume at 3, 6, and 12 Months as Assessed by an Independent Core Laboratory | Month 3, Month 6 and Month 12 | Hematoma volume was assessed by independent core laboratory. An independent imaging core laboratory was utilized to provide an unbiased and standardized assessment of study imaging. Hematoma volume was calculated using the ABC/2 method (multiplying Diameters A, B, and C and dividing by 2), where Diameter A was defined as the largest length in the axial plane to each corner of the SDH, Diameter B was defined as the maximum with 90 degree to Diameter A in the same slice, Diameter C was defined as the maximum height of the hematoma. For the calculation of the height, the number of slices with visible hematoma was multiplied by the thickness of the CT-scan. Hematoma volume reduction (%) was calculated as: (post-baseline hematoma volume minus baseline volume) divided by baseline volume \*100%. A reduction \>50% was defined as a decrease in hematoma volume of more than half compared with baseline. Baseline was defined as the last non-missing measurement collected prior to randomization. |
| Number of Participants With Complete Resolution of the cSDH at 3, 6, and 12 Months as Assessed by an Independent Core Laboratory | At Months 3, 6 and 12 | Number of participants with complete resolution of the cSDH at 3, 6, and 12 months as assessed by an independent core laboratory was reported. Complete resolution was defined as the absence of measurable cSDH on CT imaging, with no residual collection visible on the evaluated slices. |
| Median Time to Achieve Complete Resolution of the cSDH | From baseline up to Month 12 | Median time to achieve complete resolution was estimated as the time point corresponding to a 50% probability of resolution of the cSDH based on the core laboratory evaluations. cSDH was evaluated using CT imaging reviewed by an independent blinded core laboratory. Complete resolution was defined as the absence of measurable cSDH on CT imaging. Time to complete resolution was calculated as the number of days from baseline to the first imaging assessment demonstrating complete resolution. |
| Percentage of Participants Who Developed an Acute Component of Their Existing cSDH or a New cSDH (Kaplan-Meier Estimate) at 3, 6, and 12 Months as Assessed by an Independent Core Laboratory | At Months 3, 6, and 12 | Percentage of participants who developed an acute component of their existing cSDH or a new cSDH at 3, 6, and 12 months as assessed by an independent core laboratory was reported. The first incidence of an acute component of an existing cSDH or a new cSDH was considered as event. Percentages reported are Kaplan-Meier estimates of cumulative incidence. |
| Percentage of Participants Who Required a Surgical Procedure on the cSDH (Kaplan-Meier Estimate) Within 3 and 6 Months Post-Randomization | From randomization up to Months 3 and 6 | Participants who underwent re-operation or surgical procedure on the cSDH within 3 and 6 months post randomization were reported. Percentages reported are Kaplan-Meier estimates of cumulative incidence. |
| Number of Participants Who Required More Than One Surgical Procedure on the cSDH Within 3, 6, and 12 Months Post-Randomization | From randomization up to Months 3, 6 and 12 | Number of participants who required more than one surgical procedure on the cSDH within 3, 6, and 12 months post-randomization were reported. |
| Number of Participants Who Required a Surgical Procedure on the cSDH Within 12 Months | From randomization up to Month 12 | Number of participants who required a surgical procedure on the cSDH within 12 months were reported. |
| Number of Participants With Shift From Baseline in Modified Rankin Scale (mRS) Score at 3, 6, and 12 Months | Baseline, Months 3, 6 and 12 | mRS was used to assess the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability. The scales ranges from 0-6, as follows: 0 = No symptoms; 1 = No significant disability. Able to carry out all usual activities, despite some symptoms; 2 = Slight disability. Able to look after own affairs without assistance, but unable to carry out all previous activities; 3 = Moderate disability. Requires some help, but able to walk unassisted; 4 = Moderately severe disability. Unable to attend to own bodily needs without assistance, and unable to walk unassisted; 5 = Severe disability. Requires constant nursing care and attention, bedridden, incontinent; 6 = Dead; higher values reflecting more severe disability or death. Baseline was defined as the last non-missing measurement collected prior to randomization. |
| Number of Participants With Death, Stroke, Myocardial Infarction (MI) or Thromboembolic Complications Within 6 and 12 Months as Assessed by the Clinical Events Committee (CEC) | From randomization up to Months 6 and 12 | Number of participants with death, stroke, MI or thromboembolic complications within 6 and 12 months as assessed by the CEC were reported. |
| Percentage of Participants With New Onset of Seizures (Kaplan-Meier Estimate) Within 3, 6, and 12 Months as Assessed by the Clinical Events Committee (CEC) | From randomization up to Months 3, 6, and 12 | Percentage of participants with new onset of seizures within 3, 6, and 12 months as assessed by the CEC were reported. Percentages reported are Kaplan-Meier estimates of cumulative incidence. |
| Number of Participants With Shift From Baseline in Mini-Mental State Exam (MMSE) Score at 6 Months | Baseline, 6 months | MMSE was a standardized tool to assess mental state in elderly patients. It included tests of orientation, attention, memory, language, and visual-spatial skills. It is comprised of questions (For example (e.g.), "What is the year?") and tasks (e.g., "Make up and write a sentence about anything"). MMSE scores range between 0 and 30. Scores 0-17 indicated severe cognitive impairment, scores 18-23 indicated mild impairment, and scores 24-30 were considered normal. Higher scores indicated better cognitive function. Baseline was defined as the last non-missing measurement collected prior to randomization. |
| Number of Participants With Shift From Baseline in Markwalder Neurological Grading Scale (MGS) at 3, 6, and 12 Months | Baseline, Months 3, 6 and 12 | Number of participants with shift from baseline in MGS at 3, 6, and 12 months was reported. The MGS is a grading system developed to evaluate neurological performance in patients with cSDH. MGS is a 5 point scale ranging from 0 to 4, where lower scores indicate less neurological impairment and higher scores indicate greater impairment. The scale is defined as follows: Grade 0: patient neurologically normal; Grade 1: patient alert and oriented with mild symptoms such as headache or mild neurologic deficit; Grade 2: patient drowsy or disoriented with variable neurologic deficit; Grade 3: patient stuporous but responsive to noxious stimuli with focal neurologic signs; and Grade 4: patient comatose with absent motor response to painful stimuli. Baseline was defined as the last non-missing measurement collected prior to randomization. |
| Hospital Days and Intensive Care Unit (ICU) Days | From randomization up to 6 months | Hospital days included total length of stay in hospital (including ICU) for index procedure. ICU days included length of stay at ICU during hospitalizations for index procedure. |
| Change From Baseline in EuroQol-5 Dimension-5 Levels (EQ-5D-5L) Score at 6 Months | Baseline, Month 6 | The EQ-5D-5L measured self-assessed health-related quality of life based on five categories: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each area was rated on a scale that described the degree of problems in that area (that is (i.e.)., "I had no problems walking about," "slight problems," "moderate problems," "severe problems," or "unable to walk"). This tool also had an overall health scale ranged from 1 to 100 to describe the condition of their health, 100 being the best imaginable. Higher scores indicating better QoL. Baseline was defined as the last non-missing measurement collected prior to randomization. |
Countries
China, United States
Contacts
PRINCIPAL_INVESTIGATORChristopher Kellner, MD
MOUNT SINAI HOSPITAL
PRINCIPAL_INVESTIGATORAnsaar Rai, MD
West Virginia University
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 69.9 Years STANDARD_DEVIATION 10.64 |
| Markwalder Grading Scale (MGS) Score on scale: 0 | 14 Participants |
| Markwalder Grading Scale (MGS) Score on scale: 1 | 35 Participants |
| Markwalder Grading Scale (MGS) Score on scale: 2 | 27 Participants |
| Markwalder Grading Scale (MGS) Score on scale: Unknown | 0 Participants |
| Modified Rankin Score (mRS) Score on scale: 0 | 20 Participants |
| Modified Rankin Score (mRS) Score on scale: 1 | 15 Participants |
| Modified Rankin Score (mRS) Score on scale: 2 | 13 Participants |
| Modified Rankin Score (mRS) Score on scale: 3 | 32 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants |
| Race/Ethnicity, Customized Asian | 2 Participants |
| Race/Ethnicity, Customized Black or African American | 55 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 13 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 118 Participants |
| Race/Ethnicity, Customized Not Reported | 3 Participants |
| Race/Ethnicity, Customized Other | 2 Participants |
| Race/Ethnicity, Customized White | 252 Participants |
| Sex: Female, Male Female | 34 Participants |
| Sex: Female, Male Male | 102 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 4 / 133 | 11 / 132 | 9 / 55 | 7 / 56 |
| other Total, other adverse events | 39 / 130 | 33 / 133 | 19 / 51 | 18 / 57 |
| serious Total, serious adverse events | 44 / 130 | 52 / 133 | 27 / 51 | 19 / 57 |
Outcome results
None listed