Use of Tissue Plasminogen Activator in the Clearance of Chronic Subdural Hematomas

Study Overview
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Brief Summary
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To determine the utility of tissue plasminogen activator (tPA) in the clearance of chronic subdural hematomas (CSDH). Intra-catheter tPA will be administered during surgical procedure and allowed to break down blood clot to assist with removal/drainage during twist drill craniostomy procedure.

Detailed Description
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A chronic subdural hematoma (CSDH) is a collection of blood overlying the brain that can be seen, usually in the elderly with even minimal head trauma. These are usually treated by removing the collection of blood. This can be done through a small drill hole in the skull or by larger holes (one or two) the size of a nickel. Sometimes a larger piece of skull is removed to be able to remove the CSDH. The standard practice at our center is to do these procedures under local anesthesia with a twist drill craniostomy (small drill hole through the skull). In some cases, all the CSDH can not be removed the first time, requiring a second procedure or a larger procedure. This study plans to use a type of medication that breaks down the solid blood clot, enabling more of it to drain. This medication (tpa) is already used in other surgeries and is safe to use in humans. Our preliminary experience and that of others suggests very low risk at the dosages being used. We hope that using this new drug will decrease the chance of the CSDH collecting again and reduce the overall length of your stay in the hospital and reduce the need for further surgery.

Official Title
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The Utility of Intra-Catheter Fibrinolytics in Draining Chronic Subdural Hematomas: A Randomized Controlled Trial Pilot Study

Conditions
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Hematoma, Subdural, Fibrinolytic; Hemorrhage

Intervention / Treatment
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* Drug: Tissue Plasminogen Activator
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult patients (18 yrs or older) Admitted to neurosurgery wing at the hospital Symptomatic patients requiring surgical drainage by twist drill craniostomy Exclusion Criteria: Patients at increased risk of bleeding such as patients taking anticoagulation medication that required reversal at time of intervention، or those with coagulopathic disorder. Patients on antiplatelets or anticoagulation medications (DOACs or warfarin) with appropriate holding period prior to drainage, those who are eventually minimized to a regular bleeding risk compared to the normal population, will be included in the study. Patients with subdural empyema. Redo twist drill craniostomy for residual cSDH within the same admission. Drain accidentally removed during nursing care or patient transport before 24 hr interval scan. Patients who are not expected to live more than three months.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 100 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention - tPA administered<br>This group will receive 2mL of intra-catheter tPA during twist drill craniostomy procedure | Drug: Tissue Plasminogen Activator<br>* Dosage of 1mg/mL mixed in 0.9% saline solution, intra-catheter administration, sterile<br>|
| Placebo Comparator: Placebo Control<br>This group will receive 2mL of intra-catheter saline solution during twist drill craniostomy procedure | Drug: Placebo<br>* 0.9% saline solution, intra-catheter administration, sterile<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Study Feasibility | Patient recruitment rate, eligibility of patients, protocol adherence, unexpected events | 8 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reoperation rate | Reoperation rate in the first 6 weeks post drainage | 8 months | 
| Volume of chronic subdural hematoma | Volume, as measured in 3 intervals: pre-procedure, post-procedure at 24hrs and 6 weeks | 8 months | 
| Rate of adverse events | Rate of adverse events in the first 6 weeks post procedure, including CNS infection, seizure, post-op hemorrhage | 8 months | 
| Length of hospital stay | length of hospital stay in days | 8 months |