A Randomized Trial of CT Fluoroscopy-guided Targeted Autologous Blood and Fibrin Glue Patching for Treatment
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|ClinicalTrials.gov Identifier: NCT03276975|
Recruitment Status : Recruiting
First Posted : September 8, 2017
Last Update Posted : September 5, 2018
|Condition or disease||Intervention/treatment||Phase|
|Cerebrospinal Fluid Leaks||Drug: TISSEEL||Phase 2|
Spontaneous intracranial hypotension (SIH) is a condition caused by non-iatrogenic spinal CSF leaks that classically presents with orthostatic headaches. These headaches, in conjunction with other presenting symptoms such as nausea, diplopia, tinnitus, and cognitive deficits, often result in profound disability. SIH is considerably underreported due to pervasive misdiagnosis. Thus, while the estimated annual incidence is reported to be 5 in 100,000, the actual number is likely considerably greater.
The current standard-of-care treatment for SIH cases that are refractory to conservative measures (i.e. bed rest and hydration) is percutaneous epidural blood patching (EBP) of the spinal CSF leak. Percutaneous EBP can be performed in several ways: 1) with or without imaging guidance, 2) targeted to a site of known or suspected CSF leak or non-targeted, and 3) with or without the addition of fibrin glue sealant.
The leading theory for the mechanism behind percutaneous EBP treatment of SIH is that it creates a durable seal of the CSF leak resulting in normalization of CSF hydrodynamics and a resultant diminution in symptoms. Fibrin glue, a sealant used for treatment of unintended durotomies during neurosurgery, is thought to improve the likelihood of a successful patch over patches containing blood alone. Therefore, imaging-guided targeted delivery of patching material containing both blood and fibrin glue directly to the site of CSF leak, a novel therapy, is presumed to be the optimal therapy. For this reason, this procedure has become standard-of-care at many tertiary-care institutions over the past several years.
Our group has extensive experience with CT fluoroscopy-guided targeted blood and fibrin glue patching of proven CSF leaks in SIH patients. However, significant uncertainty remains with regard to the efficacy of this procedure due to a paucity of outcomes data and the absence of any prospective RCTs. In fact, nearly all of the current evidence for the treatment of SIH is found in the form of retrospective chart reviews. Given the growing recognition of SIH, the fact that a known subset of patients will have spontaneous resolution of symptoms, and the absence of clear evidence to guide treatment, there is a critical need to evaluate the efficacy of targeted patching with blood and fibrin glue with a prospective RCT. Fulfilling this unmet need forms the basis for this proposal. While determining the efficacy of the other types of EBPs is also important, we aim to begin by evaluating the efficacy of the presumed optimal therapy.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||200 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Triple (Participant, Care Provider, Outcomes Assessor)|
|Official Title:||A Randomized Trial of CT Fluoroscopy-guided Targeted Autologous Blood and Fibrin Glue Patching for Treatment of Cerebrospinal Fluid Leaks in Spontaneous Intracranial Hypotension.|
|Actual Study Start Date :||December 18, 2017|
|Estimated Primary Completion Date :||April 30, 2020|
|Estimated Study Completion Date :||April 30, 2020|
|Experimental: Patching of CSF Leaks with Autologous Blood and Fibrin||
TISSEEL is a fibrin sealant indicated for use as an adjunct to hemostasis in adult and pediatric patients (>1 month of age) undergoing surgery when control of bleeding by conventional surgical techniques (such as suture, ligature, and cautery) is ineffective or impractical. TISSEEL is effective in heparinized patients
|No Intervention: Simulated Patching Procedure|
- Positive response rate for HIT-6 as measured by the headache questionnaire [ Time Frame: 1 month ]
- Reduction of HIT-6 as measured by the headache questionnaire [ Time Frame: baseline, 1 week, 2 weeks, 1 month, 4 months ]
- Change in HIT-6 score as measured by the headache questionnaire [ Time Frame: 2 weeks, 4 months ]
- Change in MIDAS score [ Time Frame: 2 weeks, 4 months ]The MIDAS questionnaire assesses headache-related disability. Patients answer five questions, scoring the number of days, in the past 3 months, where their activity was limited due to headache. This tool has been shown to be internally consistent, highly reliable, valid, and correlates with physicians' clinical judgment.
- Change in NRS score [ Time Frame: 2 weeks, 4 months ]The pain numerical rating scale (NRS) is a well-validated tool for quantitatively assessing patients' pain. The NRS asks patients to rate their current pain intensity on an 11-point scale ranging from 0 ("no pain") to 10 ("worst possible pain"). It has been found to be a valid measure of pain intensity with minimum clinically important difference noted to be a change of 2 points. The investigators will use NRS averaged over the past 24 hours for all time points in this trial. The Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) consensus statement indicates that an NRS reduction of 30% (or 2 points) is associated with a meaningful or moderately important improvement in pain. Further, IMMPACT also indicates that an NRS reduction of 50% (or 4 points) is associated with a substantial improvement in pain. The investigators will follow their consensus recommendations and explicitly report these two categories of pain relief.
- Change in EQ-5D score [ Time Frame: 2 weeks, 4 months ]A standardized measure of health status that provides a simple, generic measure of health for clinical appraisal. It is well-validated for health status measurement and for quality-of-life in headache.
- Change in PGIC score [ Time Frame: 2 weeks, 4 months ]A validated 7-point Likert-type scale assessing a patient's overall impression of improvement after intervention.
- Change in WPAI score [ Time Frame: 2 weeks, 4 months ]A validated instrument with good test-retest reliability used extensively in health research that quantifies impairment in daily activities and work productivity.
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): NCT03276975
|Contact: Timothy J Amerhein, M.D.||firstname.lastname@example.org|
|Contact: Christopher T Vallanat, M.B.B.S.(MD)||919-684-5485||Christopher.email@example.com|
|United States, North Carolina|
|Durham, North Carolina, United States, 27710|
|Contact: Christopher Vallanat 919-684-5485 firstname.lastname@example.org|