Progel Vascular Sealant

• Sponsor: C. R. Bard (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01959503
• Collaborator: (none)
• Enrollment: 158
• Locations: 19
• Arms: 2
• Duration (Months): 13
• Patients Per Site: 8.3
• Patients Per Site Per Month: 0.6

Study Details

Study Description

Brief Summary

This study is being conducted to evaluate the safety and effectiveness of the Progel Vascular Sealant for use in vascular reconstructions to achieve adjunctive hemostasis by mechanically sealing areas of leakage.

Condition or Disease	Intervention/Treatment	Phase
Aortic Valve Stenosis; Aneurysm of Ascending Aorta; Aortic Valve Disorder; Bicuspid Valve Disorder	Device: Progel Vascular Sealant; Device: Gelfoam Plus	N/A

Detailed Description

The primary objective of this clinical study is to compare the time to hemostasis at the aortic anastomotic suture line in subjects receiving Progel (Test group) to that in subjects receiving Gelfoam Plus (Control group) on anastomotic suture lines involving the aortic valve, ascending aorta, or aortic arch while on cardiopulmonary bypass.

The primary endpoint of this study is the time to achieve hemostasis at the aortic anastomotic suture line from the time surgical clamps are released to cessation of leakage at the treated anastomotic site with either Progel (Test) or Gelfoam Plus (Control).

Study Design

• Study Type: Interventional
• Actual Enrollment: 158 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Participant)
• Primary Purpose: Treatment
• Official Title: A Prospective, Randomized Study to Compare Progel Vascular Sealant to Gelfoam Plus as an Adjunct for the Control of Bleeding in Subjects Undergoing Thoracic Aortic Surgery
• Study Start Date: Nov 1, 2013
• Actual Primary Completion Date: Dec 1, 2014
• Actual Study Completion Date: Dec 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Progel Vascular Sealant Progel Vascular Sealant after confirmation of anastomotic leakage during intra-procedure leak test.	Device: Progel Vascular Sealant; Other Names: Progel
Active Comparator: Gelfoam Plus Gelfoam Plus Sealant after confirmation of anastomotic leakage during intra-procedure leak test.	Device: Gelfoam Plus; Other Names: Gelfoam

Outcome Measures

Primary Outcome Measures

1. Time to Achieve Hemostasis at the Aortic Anastomotic Suture Line From the Time Surgical Clamps Are Released to Cessation of Leakage at the Treated Anastomotic Site With Either Progel or Gelfoam. [0 seconds to 600 seconds]

Secondary Outcome Measures

1. Proportion of Subjects Who Achieve Successful Hemostasis at All Treated Aortic Anastomotic Suture Lines Following Assigned Treatment. [5 minutes after application]

2. Proportion of Subjects Who Achieve Immediate Hemostasis, Defined as 0 Seconds, at All Treated Aortic Anastomotic Suture Lines Following Assigned Treatment. [0 seconds to 10 minutes]

3. Chest Tube Drainage Volume Following Surgery. [24 hours post procedure]

4. Proportion of Subjects Who Received Transfusion Within 24 Hours Following Surgery [24 hours post procedure]

5. Time Between Cross Clamp Removal and Request of Surgical Wires for Sternal Closure. [Intra-procedurally]

6. Incidence of Reoperations for Aortic Bleeding Complications Following Treatment. [30 days post procedure]

7. Proportion of Subjects With Device-Related Serious Adverse Events Following Assigned Treatment Through 30 Days [30 days post procedure]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• 1. Subject must be ≥ 18 years of age.
• 1. Subject is scheduled for elective, primary thoracic surgery involving the aortic valve, ascending aorta, or aortic arch on cardiopulmonary bypass.
• 1. Subject has an expected life expectancy> 6 months.
• 1. Subject is willing and able to comply with all aspects of the study including follow-up schedule.
• 1. Subject or authorized representative, has the ability to provide voluntary written informed consent.

Intra-operative Inclusion Criteria:

• 1. Subject is able to undergo an antegrade cardioplegia injection for evaluation of a leak at the aortic anastomotic site(s) during the procedure.
• 1. Following this injection, subject has a leaking site where a topical sealant/hemostatic agent may be used to control bleeding.

Exclusion Criteria:

• 1. Subject has Type A or other acute thoracic aortic dissection.
• 1. Subject has undergone prior thoracic surgery (open thoracotomy not including interventional cardiology procedures).
• 1. Subject is undergoing a planned concomitant procedure other than coronary artery bypass graft (CABG).
• 1. Subject has a previous organ transplant.
• 1. Subject has known or suspected preoperative coagulation disorder.
• 1. Subject is allergic to human thrombin or has a history of allergic reactions after application of human thrombin.
• 1. Subject is allergic to protamine.
• 1. Subject has a Left Ventricular Assist Device (LVAD) or planned to receive an LVAD.
• 1. Subject is undergoing emergency surgery.
• 1. Subject is in chronic renal failure.
• 1. Subject has a hematocrit < 21% pre-operatively.
• 1. Subject has a serum creatinine ≥2.5 mg/dl at baseline or is currently on dialysis.
• 1. Subject has a cardiac ejection fraction <25%.
• 1. Subject is scheduled for another cardiac surgery within 30 days of enrollment.
• 1. Subject has an active or latent infection which is systemic or at the intended surgery site.
• 1. Subject is immuno-compromised such as that resulting from chronic oral steroid use, chemotherapeutic agents, or immune deficiency disorders.
• 1. Subject is pregnant by a positive pregnancy test or has plans to become pregnant during the study period or is currently breast-feeding.
• 1. Subject is unwilling to receive blood products.
• 1. Subject has participated in another investigational research study within 30 days of enrollment.
• 1. In the opinion of the investigator, the subject has a clinical condition that would preclude the use of the study device, preclude the subject from completing the follow-up requirements, or would complicate the evaluation of this study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Cedars-Sinai	Los Angeles	California	United States	90048
2	University of Colorado	Aurora	Colorado	United States	80045
3	University of Florida	Gainesville	Florida	United States	32610
4	Portneuf Hospital	Pocatello	Idaho	United States	83201
5	Northwestern University	Chicago	Illinois	United States	60611
6	University of Michigan	Ann Arbor	Michigan	United States	48109
7	Mayo Clinic Hospital	Rochester	Minnesota	United States	55905
8	Washington University	St. Louis	Missouri	United States	63110
9	Bryan Heart	Lincoln	Nebraska	United States	68510
10	Montefiore Medical Center	Bronx	New York	United States	10467
11	Cornell University	New York	New York	United States	10021
12	Carolinas Health Care System	Charlotte	North Carolina	United States	28203
13	Ohio Health Research Institute	Columbus	Ohio	United States	43214
14	University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104
15	Houston Methodist Hospital	Houston	Texas	United States	77030
16	The Heart Hospital Baylor	Plano	Texas	United States	75093
17	Intermountain Medical Center	Murray	Utah	United States	84107
18	University of Virginia Health Sciences Center	Charlottesville	Virginia	United States	22904
19	Virginia Commonwealth University Medical Center	Richmond	Virginia	United States	23298

Sponsors and Collaborators

• C. R. Bard

Investigators

• Principal Investigator: Ali Khoynezhad, MD, Cedars-Sinai Heart Institute

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: C. R. Bard
• ClinicalTrials.gov Identifier: NCT01959503
• Other Study ID Numbers: NEO13-100
• First Posted: Oct 10, 2013
• Last Update Posted: Apr 10, 2017
• Last Verified: Apr 1, 2017

• Keywords provided by C. R. Bard: Aorta; Aortic; Reconstruction; CABG; Bypass
• Additional relevant MeSH terms: Aneurysm; Aortic Valve Stenosis; Aortic Valve Disease; Disease; Gelatin Sponge, Absorbable

Study Results

Participant Flow

Arm/Group Title	Progel Vascular Sealant	Gelfoam Plus
Arm/Group Description	Progel Vascular Sealant after confirmation of anastomotic leakage during intra-procedure leak test. Progel Vascular Sealant	Gelfoam Plus Sealant after confirmation of anastomotic leakage during intra-procedure leak test. Gelfoam Plus
Period Title: Overall Study
STARTED	107	51
COMPLETED	104	49
NOT COMPLETED	3	2

Baseline Characteristics

Arm/Group Title	Progel Vascular Sealant	Gelfoam Plus	Total
Arm/Group Description	Progel Vascular Sealant after confirmation of anastomotic leakage during intra-procedure leak test. Progel Vascular Sealant	Gelfoam Plus Sealant after confirmation of anastomotic leakage during intra-procedure leak test. Gelfoam Plus	Total of all reporting groups
Overall Participants	106	50	156
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	61.5 (14.42)	62.4 (14.30)	61.8 (14.34)
Sex: Female, Male (Count of Participants)
Female	32 30.2%	15 30%	47 30.1%
Male	74 69.8%	35 70%	109 69.9%
Region of Enrollment (participants) [Number]
United States	106 100%	50 100%	156 100%

Outcome Measures

1. Primary Outcome

Title	Time to Achieve Hemostasis at the Aortic Anastomotic Suture Line From the Time Surgical Clamps Are Released to Cessation of Leakage at the Treated Anastomotic Site With Either Progel or Gelfoam.
Time Frame	0 seconds to 600 seconds

Outcome Measure Data

Analysis Population Description

In the Progel group one subject was not evaluable as information was not collected for the primary end-point changing the number from 106 to 105, compare to baseline characteristics.

Arm/Group Title	Progel Vascular Sealant	Gelfoam Plus
Arm/Group Description	Progel Vascular Sealant after confirmation of anastomotic leakage during intra-procedure leak test. Progel Vascular Sealant	Gelfoam Plus Sealant after confirmation of anastomotic leakage during intra-procedure leak test. Gelfoam Plus
Measure Participants	105	50
Mean (Standard Deviation) [seconds]	124.3 (202.09)	377.8 (252.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Progel Vascular Sealant, Gelfoam Plus
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Wilcoxon Rank-Sum Test
	Comments

2. Secondary Outcome

Title	Proportion of Subjects Who Achieve Successful Hemostasis at All Treated Aortic Anastomotic Suture Lines Following Assigned Treatment.
Time Frame	5 minutes after application

Outcome Measure Data

Analysis Population Description

In the Progel group one subject was not evaluable as information was not collected for this endpoint, which change the number from 106 to 105, compare to baseline characteristics.

Arm/Group Title	Progel Vascular Sealant	Gelfoam Plus
Arm/Group Description	Progel Vascular Sealant after confirmation of anastomotic leakage during intra-procedure leak test. Progel Vascular Sealant	Gelfoam Plus Sealant after confirmation of anastomotic leakage during intra-procedure leak test. Gelfoam Plus
Measure Participants	105	50
Number [percentage of participants]	85.7 80.8%	40.0 80%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Progel Vascular Sealant, Gelfoam Plus
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	9.00
	Confidence Interval	(2-Sided) 95%; 4.07 to 19.89
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Proportion of Subjects Who Achieve Immediate Hemostasis, Defined as 0 Seconds, at All Treated Aortic Anastomotic Suture Lines Following Assigned Treatment.
Time Frame	0 seconds to 10 minutes

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Progel Vascular Sealant	Gelfoam Plus
Arm/Group Description	Progel Vascular Sealant after confirmation of anastomotic leakage during intra-procedure leak test. Progel Vascular Sealant	Gelfoam Plus Sealant after confirmation of anastomotic leakage during intra-procedure leak test. Gelfoam Plus
Measure Participants	106	50
Number [percentage of participants]	59.4 56%	16.0 32%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Progel Vascular Sealant, Gelfoam Plus
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	7.69
	Confidence Interval	(2-Sided) 95%; 3.27 to 18.11
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Chest Tube Drainage Volume Following Surgery.
Time Frame	24 hours post procedure

Outcome Measure Data

Analysis Population Description

In the Gelfoam Plus group one subject was not evaluable as information was not collected for this endpoint, which change the number from 50 to 49, compare to baseline characteristics.

Arm/Group Title	Progel Vascular Sealant	Gelfoam Plus
Arm/Group Description	Progel Vascular Sealant after confirmation of anastomotic leakage during intra-procedure leak test. Progel Vascular Sealant	Gelfoam Plus Sealant after confirmation of anastomotic leakage during intra-procedure leak test. Gelfoam Plus
Measure Participants	106	49
Mean (Standard Deviation) [mL]	701.6 (499.83)	589.6 (359.41)

5. Secondary Outcome

Title	Proportion of Subjects Who Received Transfusion Within 24 Hours Following Surgery
Time Frame	24 hours post procedure

Outcome Measure Data

Analysis Population Description

In the Gelfoam Plus group one subject was not evaluable as information was not collected for this endpoint, which change the number from 50 to 49, compare to baseline characteristics.

Arm/Group Title	Progel Vascular Sealant	Gelfoam Plus
Arm/Group Description	Progel Vascular Sealant after confirmation of anastomotic leakage during intra-procedure leak test. Progel Vascular Sealant	Gelfoam Plus Sealant after confirmation of anastomotic leakage during intra-procedure leak test. Gelfoam Plus
Measure Participants	106	49
Number [participants]	46 43.4%	19 38%

6. Secondary Outcome

Title	Time Between Cross Clamp Removal and Request of Surgical Wires for Sternal Closure.
Time Frame	Intra-procedurally

Outcome Measure Data

Analysis Population Description

In the Vascular group two subjects were not evaluable as information was not collected for this endpoint, which changes the number from 106 to 104, compare to baseline characteristics.

Arm/Group Title	Progel Vascular Sealant	Gelfoam Plus
Arm/Group Description	Progel Vascular Sealant after confirmation of anastomotic leakage during intra-procedure leak test. Progel Vascular Sealant	Gelfoam Plus Sealant after confirmation of anastomotic leakage during intra-procedure leak test. Gelfoam Plus
Measure Participants	104	50
Mean (Standard Deviation) [minutes]	59.4 (30.96)	58.5 (24.74)

7. Secondary Outcome

Title	Incidence of Reoperations for Aortic Bleeding Complications Following Treatment.
Time Frame	30 days post procedure

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Progel Vascular Sealant	Gelfoam Plus
Arm/Group Description	Progel Vascular Sealant after confirmation of anastomotic leakage during intra-procedure leak test. Progel Vascular Sealant	Gelfoam Plus Sealant after confirmation of anastomotic leakage during intra-procedure leak test. Gelfoam Plus
Measure Participants	106	50
Number [participants]	0 0%	1 2%

8. Secondary Outcome

Title	Proportion of Subjects With Device-Related Serious Adverse Events Following Assigned Treatment Through 30 Days
Time Frame	30 days post procedure

Outcome Measure Data

Analysis Population Description

One subject in Progel Vascular Sealant and one subject in Gelfoam Plus discontinue before 30days and do not have device-related SAE. They are considered as not evaluable and are not included in this analysis, thus makes the difference compared to population in baseline.

Arm/Group Title	Progel Vascular Sealant	Gelfoam Plus
Arm/Group Description	Progel Vascular Sealant after confirmation of anastomotic leakage during intra-procedure leak test. Progel Vascular Sealant	Gelfoam Plus Sealant after confirmation of anastomotic leakage during intra-procedure leak test. Gelfoam Plus
Measure Participants	105	49
Number [participants]	3 2.8%	4 8%

Adverse Events

Time Frame	Incidence of reoperations for aortic bleeding complications following assigned treatment through 30 days. Number of device-related serious adverse events per patient following assigned treatment through 30 days.
Arm/Group Title	Progel Vascular Sealant		Gelfoam Plus
Arm/Group Description	Progel Vascular Sealant after confirmation of anastomotic leakage during intra-procedure leak test. Progel Vascular Sealant		Gelfoam Plus Sealant after confirmation of anastomotic leakage during intra-procedure leak test. Gelfoam Plus
All Cause Mortality
	Progel Vascular Sealant		Gelfoam Plus
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Progel Vascular Sealant		Gelfoam Plus
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	51/106 (48.1%)		29/50 (58%)
Blood and lymphatic system disorders
Anemia	5/106 (4.7%)		1/50 (2%)
Thrombocytopenia	0/106 (0%)		1/50 (2%)
Cardiac disorders
Aortic valve incompetence	1/106 (0.9%)		0/50 (0%)
Atrial fibrillation	27/106 (25.5%)		17/50 (34%)
Atrial flutter	2/106 (1.9%)		3/50 (6%)
Atrioventricular block	2/106 (1.9%)		1/50 (2%)
Atrioventricular block complete	0/106 (0%)		1/50 (2%)
Cardiac arrest	1/106 (0.9%)		2/50 (4%)
Cardiac failure	0/106 (0%)		1/50 (2%)
Cardiac failure congestive	1/106 (0.9%)		0/50 (0%)
Cardiac tamponade	2/106 (1.9%)		0/50 (0%)
Cardiogenic shock	2/106 (1.9%)		0/50 (0%)
Cardiopulmonary failure	1/106 (0.9%)		0/50 (0%)
Ischemic cardiomyopathy	1/106 (0.9%)		0/50 (0%)
Pericardial effusion	1/106 (0.9%)		0/50 (0%)
Pericardial hemorrhage	1/106 (0.9%)		0/50 (0%)
Supraventricular extrasystoles	1/106 (0.9%)		0/50 (0%)
Ventricular fibrillation	0/106 (0%)		2/50 (4%)
Ventricular tachycardia	1/106 (0.9%)		0/50 (0%)
Gastrointestinal disorders
Gastrointestinal hemorrhage	0/106 (0%)		1/50 (2%)
Ileus	0/106 (0%)		1/50 (2%)
Melena	1/106 (0.9%)		0/50 (0%)
General disorders
Complication of device removal	1/106 (0.9%)		0/50 (0%)
Infections and infestations
Bacterial infection	1/106 (0.9%)		0/50 (0%)
Bacterial sepsis	1/106 (0.9%)		0/50 (0%)
Incision site infection	1/106 (0.9%)		0/50 (0%)
Pneumonia	2/106 (1.9%)		0/50 (0%)
Postoperative wound infection	1/106 (0.9%)		0/50 (0%)
Respiratory tract infection	0/106 (0%)		1/50 (2%)
Injury, poisoning and procedural complications
Postoperative respiratory failure	1/106 (0.9%)		0/50 (0%)
Postoperative thoracic procedure complication	1/106 (0.9%)		0/50 (0%)
Metabolism and nutrition disorders
Fluid overload	2/106 (1.9%)		0/50 (0%)
Malnutrition	1/106 (0.9%)		0/50 (0%)
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain	0/106 (0%)		1/50 (2%)
Nervous system disorders
Cerebrovascular accident	1/106 (0.9%)		2/50 (4%)
Convulsion	0/106 (0%)		1/50 (2%)
Embolic stroke	1/106 (0.9%)		0/50 (0%)
Syncope	1/106 (0.9%)		0/50 (0%)
Renal and urinary disorders
Renal injury	2/106 (1.9%)		0/50 (0%)
Renal tubular acidosis	1/106 (0.9%)		0/50 (0%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory distress syndrome	1/106 (0.9%)		0/50 (0%)
Acute respiratory failure	1/106 (0.9%)		0/50 (0%)
Atelectasis	1/106 (0.9%)		0/50 (0%)
Epistaxis	0/106 (0%)		1/50 (2%)
Hypoxia	2/106 (1.9%)		0/50 (0%)
Mediastinal hemorrhage	0/106 (0%)		1/50 (2%)
Pleural effusion	5/106 (4.7%)		1/50 (2%)
Pneumothorax	5/106 (4.7%)		3/50 (6%)
Pulmonary edema	1/106 (0.9%)		0/50 (0%)
Surgical and medical procedures
Incisional drainage	0/106 (0%)		1/50 (2%)
Vascular disorders
Deep vein thrombosis	1/106 (0.9%)		0/50 (0%)
Hematoma	1/106 (0.9%)		1/50 (2%)
Hemorrhage	0/106 (0%)		1/50 (2%)
Hypotension	0/106 (0%)		1/50 (2%)
Hypovolemic shock	1/106 (0.9%)		0/50 (0%)
Phlebitis	0/106 (0%)		1/50 (2%)
Venous thrombosis limb	1/106 (0.9%)		0/50 (0%)
Other (Not Including Serious) Adverse Events
	Progel Vascular Sealant		Gelfoam Plus
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	51/106 (48.1%)		29/50 (58%)
Blood and lymphatic system disorders
Anemia	34/106 (32.1%)		12/50 (24%)
Leukocytosis	25/106 (23.6%)		13/50 (26%)
Thrombocytopenia	19/106 (17.9%)		7/50 (14%)
Cardiac disorders
Atrial Fibrillation	13/106 (12.3%)		7/50 (14%)
Tachycardia	6/106 (5.7%)		2/50 (4%)
Gastrointestinal disorders
Nausea	15/106 (14.2%)		7/50 (14%)
Vomiting	1/106 (0.9%)		4/50 (8%)
General disorders
Fatigue	3/106 (2.8%)		5/50 (10%)
Oedema Peripheral	18/106 (17%)		4/50 (8%)
Pyrexia	2/106 (1.9%)		3/50 (6%)
Metabolism and nutrition disorders
Fluid Overload	10/106 (9.4%)		8/50 (16%)
Hyperglycemia	8/106 (7.5%)		5/50 (10%)
Hypokalemia	7/106 (6.6%)		2/50 (4%)
Hyponatremia	3/106 (2.8%)		3/50 (6%)
Musculoskeletal and connective tissue disorders
Back Pain	7/106 (6.6%)		2/50 (4%)
Musculoskeletal Pain	2/106 (1.9%)		4/50 (8%)
Nervous system disorders
Dizziness	6/106 (5.7%)		3/50 (6%)
Renal and urinary disorders
Renal Injury	5/106 (4.7%)		3/50 (6%)
Respiratory, thoracic and mediastinal disorders
Atelectasis	36/106 (34%)		15/50 (30%)
Dyspnoea	4/106 (3.8%)		3/50 (6%)
Hypoxia	6/106 (5.7%)		3/50 (6%)
Pleural Effusion	38/106 (35.8%)		17/50 (34%)
Pneumothorax	6/106 (5.7%)		3/50 (6%)
Pulmonary oedema	10/106 (9.4%)		2/50 (4%)
Respiratory failure	3/106 (2.8%)		3/50 (6%)
Vascular disorders
Hypotension	13/106 (12.3%)		4/50 (8%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

INSTITUTION and INVESTIGATOR agree if the Study is part of a multi-center study, the first publication of the results of the Study shall be made in coajunction with the results from the investigators at the other Study centers. In the event no publication of the multi-center study has been made within two years after the completion of the Study at all Study centers, then INSTITUTION and INVESTIGATOR shall be free to publish the Study results generated.