NCT03276975

A Randomized Trial of CT Fluoroscopy-guided Targeted Autologous Blood and Fibrin Glue Patching for Treatment

Completed Phase 2 Results posted Last updated 18 June 2021

What this trial tests

Phase 2 trial testing TISSEEL in Cerebrospinal Fluid Leaks in 15 participants. Completed in 19 March 2020.

Timeline

18 December 2017

Primary endpoint
19 March 2020

19 March 2020

Quick facts

Lead sponsor	Duke University
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	triple
Primary purpose	treatment
Enrollment	15
Start date	18 December 2017
Primary completion	19 March 2020
Estimated completion	19 March 2020
Sites	1 location across United States

Drugs / interventions tested

• TISSEEL — full drug profile →

Conditions studied

• Cerebrospinal Fluid Leaks — all drugs for Cerebrospinal Fluid Leaks →

Sponsor

Duke University

Who can join

18 and older, any sex, with Cerebrospinal Fluid Leaks. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Change in Median (Headache Impact Test-6) HIT-6 Score From Baseline Primary · Baseline, 1 month

Absolute change in median HIT-6 score from pre-procedural baseline to 1 month post procedure for each group. The HIT-6 consists of six items: pain, social functioning, role functioning, vitality, cognitive functioning, and psychological distress. The patient answers each of the six related questions using one of the following five responses: "never", "rarely", "sometimes", "very often", or "always". These responses are summed to produce a total HIT-6 score that ranges from 36 to 78, where a higher score indicates a greater impact of headache on the daily life of the respondent.

Group	Value	95% CI
Targeted Epidural Patching of CSF Leaks With Autologous Blood and Fibrin Glue	-12	-16 – -7
Simulated Patching Procedure	-7	-13 – -1

Change in Median HIT-6 Score From Baseline Secondary · Baseline, 2 weeks, 4 months

Absolute change in median HIT-6 score from pre-procedural baseline to 2 weeks and 4 months post procedure for each group. The HIT-6 consists of six items: pain, social functioning, role functioning, vitality, cognitive functioning, and psychological distress. The patient answers each of the six related questions using one of the following five responses: "never", "rarely", "sometimes", "very often", or "always". These responses are summed to produce a total HIT-6 score that ranges from 36 to 78, where a higher score indicates a greater impact of headache on the daily life of the respondent.

2 weeks

Group	Value	95% CI
Targeted Epidural Patching of CSF Leaks With Autologous Blood and Fibrin Glue	-5.5	-10 – 0.5
Simulated Patching Procedure	-7	-17 – -3

4 months

Group	Value	95% CI
Targeted Epidural Patching of CSF Leaks With Autologous Blood and Fibrin Glue	-4.5	-16.5 – -1.5
Simulated Patching Procedure	-12	-24 – -7

Reduction in Median Migraine Disability Assessment (MIDAS) Score From Baseline Secondary · Baseline, 2 weeks, 1 month, 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. A higher score indicates greater headache-related disability. This tool has been shown to be internally consistent, highly reliable, valid, and correlates with physicians' clinical judgment. MIDAS Scale Range: 0 - 270

2 weeks

Group	Value	95% CI
Targeted Epidural Patching of CSF Leaks With Autologous Blood and Fibrin Glue	-25	-55 – 6
Simulated Patching Procedure	16	-35 – 100

1 month

Group	Value	95% CI
Targeted Epidural Patching of CSF Leaks With Autologous Blood and Fibrin Glue	-62.5	-117 – -37
Simulated Patching Procedure	-40	-86 – -3

4 months

Group	Value	95% CI
Targeted Epidural Patching of CSF Leaks With Autologous Blood and Fibrin Glue	-87	-134.5 – -69.5
Simulated Patching Procedure	-53	-210 – -22

Change in Median NRS Score From Baseline Secondary · Baseline, 2 weeks, 1 month, 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

2 weeks

Group	Value	95% CI
Targeted Epidural Patching of CSF Leaks With Autologous Blood and Fibrin Glue	-0.5	-1.5 – 1
Simulated Patching Procedure	-1	-3 – 0

1 month

Group	Value	95% CI
Targeted Epidural Patching of CSF Leaks With Autologous Blood and Fibrin Glue	-2.5	-4.5 – -1
Simulated Patching Procedure	0	-3 – 3

4 months

Group	Value	95% CI
Targeted Epidural Patching of CSF Leaks With Autologous Blood and Fibrin Glue	-1.5	-5 – -0.5
Simulated Patching Procedure	-2	-3 – -1

Change in Median EQ-5D (European Quality of Life-5 Dimensions) Score From Baseline Secondary · Baseline, 2 weeks, 1 month, 4 months

The EQ-5D is 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. Scores on the EQ-5D were calculated using the United States 3L, time trade off (TTO) valuation technique. Scores range from 0 to 1, with 1 indicating perfect health.

2 weeks

Group	Value	95% CI
Targeted Epidural Patching of CSF Leaks With Autologous Blood and Fibrin Glue	0.1	0 – 0.2
Simulated Patching Procedure	0.1	-0.1 – 0.3

1 month

Group	Value	95% CI
Targeted Epidural Patching of CSF Leaks With Autologous Blood and Fibrin Glue	0	0 – 0.4
Simulated Patching Procedure	0.1	0 – 0.4

4 months

Group	Value	95% CI
Targeted Epidural Patching of CSF Leaks With Autologous Blood and Fibrin Glue	0	-0.1 – 0.1
Simulated Patching Procedure	0.2	0.1 – 0.4

Change in Median WPAI (Work Productivity and Activity Impairment) Score From Baseline Secondary · Baseline, 2 weeks, 1 month, 4 months

The WPAI is a validated instrument with good test-retest reliability used extensively in health research that quantifies impairment in daily activities and work productivity. Scores on the WPAI range from 0 - 100% with higher percentages indicating greater impact on work productivity and more severe activity impairment.

2 weeks

Group	Value	95% CI
Targeted Epidural Patching of CSF Leaks With Autologous Blood and Fibrin Glue	1.3	-16.9 – 13.5
Simulated Patching Procedure	-0.3	-8.8 – 3.6

1 month

Group	Value	95% CI
Targeted Epidural Patching of CSF Leaks With Autologous Blood and Fibrin Glue	-13.8	-51 – 5
Simulated Patching Procedure	-2.3	-20.8 – 20

4 months

Group	Value	95% CI
Targeted Epidural Patching of CSF Leaks With Autologous Blood and Fibrin Glue	-9	-29 – 13.7
Simulated Patching Procedure	-28.5	-47 – -10

Change in PGIC (Patient Global Impression of Change) Score From Baseline Secondary · Baseline, 2 weeks, 1 month, 4 months

PGIC is a validated 7-point Likert-type scale assessing a patient's overall impression of improvement after intervention. Scores range from 1 - 7 (1: no change or worsening of condition; 2: almost the same, hardly any change at all; 3: a little better, but no noticeable change; 4: somewhat better, but the change has not made any real difference; 5: moderately better, and a slight but noticeable change; 6: better and a definite improvement that has made a real and worthwhile difference; 7: a great deal better, and a considerable improvement that has made all the difference) with higher scores i

2 weeks

Group	Value	95% CI
Targeted Epidural Patching of CSF Leaks With Autologous Blood and Fibrin Glue	3.5	3 – 4.5
Simulated Patching Procedure	2	1 – 4

1 month

Group	Value	95% CI
Targeted Epidural Patching of CSF Leaks With Autologous Blood and Fibrin Glue	4	3 – 5.5
Simulated Patching Procedure	3	1 – 5

4 months

Group	Value	95% CI
Targeted Epidural Patching of CSF Leaks With Autologous Blood and Fibrin Glue	4.5	3.5 – 6
Simulated Patching Procedure	6	2 – 6

Adverse events — posted to ClinicalTrials.gov

Time frame: Adverse event data were collected immediately after the initial procedure, immediately after any crossover procedures (performed at the 2-month time point), and also at 1 week after any procedure (initial or crossover).. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Targeted Epidural Patching of CSF Leaks With Autologous Blood and Fibrin Glue

Serious: 0/15 (0%)

Deaths: 0/15

Simulated Patching Procedure

Serious: 0/7 (0%)

Deaths: 0/7

Other adverse events (2 terms — click to expand)

Reaction	System	Targeted Epidural Patching…	Simulated Patching Procedure
Asymptomatic self-limited hypertension	Vascular disorders	—	—
Rebound Intracranial Hypertension	Nervous system disorders	—	—

Data from ClinicalTrials.gov NCT03276975 adverse events section.

Sponsor's own description

The goal of this randomized controlled trial (RCT) is to compare the efficacy of CT fluoroscopy-guided targeted epidural patching for treatment of imaging-confirmed spinal CSF leaks to that of a simulated procedure without patching material in patients with spontaneous intracranial hypotension.

Publications & conference data

No peer-reviewed publications indexed yet for this trial. Completed trials usually publish results within 12-18 months.