# Presentation: 373520

## DuraSealTMDural Sealant System PMA  P040034

## Presenters

**Eric Ankerud, J.D.**** **– Confluent Surgical, Inc.
- 		*Vice President, Clinical, Regulatory, and Quality *
**Patrick Campbell, Ph.D. **– Confluent Surgical, Inc.
- 	 	*Vice President, Research & Development*
**John Tew, M.D. **– Mayfield Clinic
**	****	***Professor, Department of Neurosurgery, University of Cincinnati*
**G. Rees Cosgrove, M.D. **– Massachusetts General Hospital
- 		*Associate Professor of Surgery, Harvard Medical School*
**Harry van Loveren, M.D. **–Tampa General Hospital
- 		*Professor and Chairman, Director of Skull Base and **	**Cerebrovascular Surgery, University of South Florida*

## Presentation Overview

**Project Overview** –** ****Eric Ankerud, J.D.**
**Technology Overview** – **Pat Campbell, Ph.D.**
**Project Rationale** – **John Tew, M.D.**
**US Pivotal Trial Results** **–**** G. Rees Cosgrove, M.D.**
**Safety Evaluation** **–**** Harry van Loveren, M.D. **

## Company Overview

**Mission:**  Development of *in-situ* polymerized biomaterials to address the unmet needs of surgical wound healing including surgical tissue sealing, post surgical adhesion prevention, and hemostasis
**Founded:** 1998
**People:**  30 employees
**Facility:**  Waltham, Massachusetts
**Products:**  Commercially available OUS

## DuraSeal Dural Sealant System

## Pre-Clinical Summary

- DuraSeal is non-toxic and safe, up to 40X human dose
- DuraSeal is not neurotoxic, and allows complete neodura formation
- Intraoperative _***and***_ postoperative sealing efficacy demonstrated in relevant canine model
- Ability to image DuraSeal has been demonstrated, and has complete absorption over 8 weeks

## Achieving “water tight” closure is basic tenet of neurosurgical practice

Controlling intraoperative leakage is important to prevent CSF leakage and development of postoperative complications:

Suture pinholes and space between sutures act as “one-way” valve for CSF leakage
Subdural collections of CSF fluid may develop into pseudomeningoceles and overt incisional leaks with potential for serious post-operative sequelae

- Controlling _**intraoperative**_ leakage is important to prevent CSF leakage and development of postoperative complications:
- Suture pinholes and space between sutures act as “one-way” valve for CSF leakage
- Subdural collections of CSF fluid may develop into pseudomeningoceles and overt incisional leaks with potential for serious post-operative sequelae

- “Water Tight” Closure Remains Elusive

**Notes:**
Suture pinholes and space between sutures act as “one-way” valve for CSF leakage
Subdural collections of CSF fluid may develop into pseudomeningoceles and overt incisional leaks with potential for serious post-operative sequelae

## 
Meningitis – may lead to delayed neurologic complications
Prolonged hospitalization and increased patient cost 
Interference with wound healing (dehiscence)
Abscess formation
Additional surgical intervention often required

- Meningitis – may lead to delayed neurologic complications
- Prolonged hospitalization and increased patient cost
- Interference with wound healing (dehiscence)
- Abscess formation
- Additional surgical intervention often required

- CSF Leak Causes Postoperative Morbidity

**Notes:**
Speak to placement of lumbar drains and LP shunts as surgical interventions taken.
Find reference for cost of CSF leak
Risk factor for development of meningitis/abscess (relative risk 16.0) Korinek et al.
Meningitis most frequent and severe complication and is associated with high mortality rate (1-20%) Shaffrey et al.

## Methods For Sealing Sutured Dural Closure

| Current Methods |  |
| --- | --- |
| FDA-Approved Devices | Products Used Off Label |

**None**

***NO STANDARD OF CARE***
- Fibrin Sealant (e.g. Tisseel)
- Absorbable gelatin (e.g. Gelfoam)
- Collagen hemostatic agents (e.g. Surgicel)
- Other bioadhesives (e.g. BioGlue)

**Notes:**
Dr. Tew to speak to the fact that none of the products listed actually work for dural sealing.
Speaking points – BioGlue toxicity
Integra’s products

## 
To evaluate the safety and effectiveness of the DuraSeal Dural Sealant System as an adjunct to sutured dural repair during cranial surgery to provide watertight closure

- To evaluate the safety and effectiveness of the DuraSeal Dural Sealant System as an adjunct to sutured dural repair during cranial surgery to provide watertight closure

- US Pivotal Study Objective

## Prospective
Multi-center
Non-randomized, single arm study
11 participating sites 
10 United States 
1 Europe

- Multi-center
- Non-randomized, single arm study
- 11 participating sites
- 10 United States
- 1 Europe

- Study Design

## Follow-up Compliance

- Patients Enrolled
- n=132

- Intra-operativeScreen Failures
- n=21

- Patients Treated with DuraSeal
- n=111

- Immediate Post-operative Visit
- (within 7 days of surgery)
- n=111
**100% of patients evaluated**

- Patient Death
- n=1 at 27 days
- Post-op

- 6 Week Visit
- n=110
**99% of patients evaluated**

- Patient Death
- n=1 at 85 days
- Post-op

- 3 Month Visit
- n=107
**98% of patients evaluated**

- Lost to
- Follow-up
- n=2

## Primary Efficacy Analysis-Intraoperative Sealing Success

| Analysis | Results |
| --- | --- |
| Intent To Treat*
(includes 2 non-evaluable patients) | 98.2% (109*/111) 
[95% CI: 93.6-99.8]
 |
| Per Protocol
(includes all evaluable patients) | 100% (109/109) 
[95% CI: 96.7-100]
 |

- * Two patients had no leak after Valsalva maneuver, but pressure reached was only to 10 cm H2O and, therefore, were not evaluable

## Summary

- Primary efficacy endpoint was met
- Adverse events consistent in nature, frequency and severity for patients undergoing cranial surgery

## Conclusion

- In the patient population evaluated, the benefits associated with the use of the DuraSeal Sealant outweigh any potential risks associated with the use of the device