STEPS: Shunt Tube Exposure Prevention Study

• Sponsor: Tissue Tech Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01551550
• Collaborator: National Eye Institute (NEI) (NIH), Bascom Palmer Eye Institute (Other), The New York Eye & Ear Infirmary (Other), Columbia University (Other)
• Enrollment: 82
• Locations: 4
• Arms: 2
• Duration (Months): 74.1
• Patients Per Site: 20.5
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

This is a multi-site randomized clinical trial to evaluate the long-term efficacy of the thicker amniotic membrane graft (AmnioGuard™, Bio-Tissue, Inc, Miami, FL) in reducing shunt tube exposure in patients undergoing glaucoma drainage device implantation.

Condition or Disease	Intervention/Treatment	Phase
Glaucoma	Procedure: GDD; Procedure: Amniotic Membrane Graft; Procedure: Pericardial Graft	N/A

Detailed Description

Glaucoma drainage devices (GDDs) have been used in the treatment of high-risk refractory glaucoma. To avoid tube exposure, which may lead to serious eye infection, the implanted GDD tube must be covered by a patch graft, traditionally made of either donor sclera or pericardium. However, these patch grafts still carry a high rate of progressive thinning and erosion, a complication that the investigators speculate results from the lack of cellular infiltration from the surrounding host conjunctival stroma and poor integration of these patch grafts to the host tissue. The investigators further speculate that a thicker version of cryo-preserved amniotic membrane (AM), manufactured by Bio-Tissue, Inc.,could offer better tensile strength, be suitable for tectonic support, and have biological activities to promote cellular infiltration by the surrounding host conjunctival stroma, thus reducing progressive allogeneic patch graft thinning/erosion.

Through SBIR Phase I grant support (R43 EY19785), the investigators have evaluated the thicker AM as an alternative patch graft for covering the GDD tube during the primary implantation. The investigators further monitored the host cell interaction using anterior segment optical coherence tomography (OCT). The investigators have successfully accomplished the proposed aims of the above studies, which demonstrated the short-term stability/efficacy of AM in covering the tube in primary GDD surgery (Phase I-Aim 1) and confirmed the feasibility of using OCT to distinguish host cell infiltration into the AM after transplantation over the GDD tube (Phase I-Aim 2).

In this SBIR Phase II, the investigators propose to conduct a prospective, controlled study to compare the long-term safety and efficacy of the thicker AM (AmnioGuard™, Bio-Tissue, Inc, Miami, FL) to the pericardium (Tutoplast®, IOP Inc, Costa Mesa, CA) in securing the GDD tube and reducing tube exposure and graft thinning in patients with high risk glaucoma. The investigators will also study the risk factors that may contribute to GDD tube exposure.

Accomplishment of this Phase II study will position AM as an effective alternative to the existing patch grafts to reduce tube exposure and enhance the success of GDD implantation, while providing a better aesthetic appearance and allowing visualization of the tube in patients with high risk glaucoma. The investigators speculate that such a graft might also have other clinical applications outside of covering GDD tubes.

Study Design

• Study Type: Interventional
• Actual Enrollment: 82 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Participant)
• Primary Purpose: Treatment
• Official Title: Amniotic Membrane Versus Pericardium in Reducing Glaucoma Drainage Tube Exposure: A Randomized Clinical Trial
• Study Start Date: Jun 1, 2013
• Actual Primary Completion Date: Dec 1, 2016
• Actual Study Completion Date: Aug 3, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: GDD & Amniotic Membrane Graft After GDD implantation, amniotic membrane graft (AmnioGuard™, Bio-Tissue inc, Miami, FL) is used to cover the GDD tube.	Procedure: GDD; The surgery includes conjunctival incision, placement and securing the GDD plate in one quadrant, paracentesis and tube insertion into the anterior chamber, tube fixation to the episclera.; Other Names: Glaucoma drainage device Tube shunt Shunt tube Ahmed Valve Baerveldt valve ; Procedure: Amniotic Membrane Graft; For subjects assigned to the treatment group, Amnioguard is used to cover the shunt tube. The conjunctiva is then closed.; Other Names: Amnioguard
Active Comparator: GDD & Pericardial Graft After GDD implantation, a pericardial graft (Tutoplast®, IOP Inc, Costa Mesa, CA) is used to cover the GDD tube.	Procedure: GDD; The surgery includes conjunctival incision, placement and securing the GDD plate in one quadrant, paracentesis and tube insertion into the anterior chamber, tube fixation to the episclera.; Other Names: Glaucoma drainage device Tube shunt Shunt tube Ahmed Valve Baerveldt valve ; Procedure: Pericardial Graft; For subjects assigned to the control group Tutoplast is used to cover the tube. The conjunctiva is then closed.; Other Names: Tutoplast

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Tube Erosion [2 years]

   Impending conjunctival erosion can be indicated by loss of conjunctival capillaries over the tube, usually 1 to 3 mm from the corneoscleral junction. Definitive tube exposure is accompanied by conjunctival tissue loss, graft melting.

Secondary Outcome Measures

1. Number of Participants With Glaucoma Drainage Device Failure [2 years]

   GDD Failure, based on reoperation to control the IOP, and also include the defined by the following criteria: (1) IOP ≥21 mm Hg or not reduced by 30% below baseline on two consecutive follow-up visits after 3 months. (2) IOP ≤5 mm Hg on two consecutive follow-up visits after 3 months. (3) Additional glaucoma surgery. (4) Loss of light perception vision.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 21 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patients with uncontrolled glaucoma undergoing GDD implantation and carry one of the following two strata of high risk factors:

1. Primary open angle glaucoma with previous conjunctival cutting surgery including prior failed trabeculectomy.

2. Secondary glaucoma, e.g., neovascular, uveitic, or post-traumatic glaucoma.

• Age range: 21- 80 years old.

• Both genders and all ethnic groups comparable with the local community.

• Patients able and willing to cooperate with investigational plan.

• Patients able and willing to complete postoperative follow-up.

• Patients able to understand and willing to sign a written informed consent.

Exclusion Criteria:

• Ocular infection within 14 days prior to prior to study entry.

• No light perception vision

• Previous cyclodestructive procedure.

• Children under 21 (see Inclusion of Children).

• Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements.

• Inability or unwillingness of subject or legal guardian/representative to give written informed consent.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Bascom Palmer Eye Institute	Miami	Florida	United States	33136
2	New York Eye and Ear Infirmary	New York	New York	United States	10003
3	Manhattan Eye, Ear, and Throat Hospital	New York	New York	United States	10021
4	Harkness Eye Institute/ Columbia University	New York	New York	United States	10032

Sponsors and Collaborators

• Tissue Tech Inc.
• National Eye Institute (NEI)
• Bascom Palmer Eye Institute
• The New York Eye & Ear Infirmary
• Columbia University

Investigators

• Principal Investigator: Hosam El Sheha, MD, PhD, Tissue Tech Inc.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Tissue Tech Inc.
• ClinicalTrials.gov Identifier: NCT01551550
• Other Study ID Numbers: P010-2, Version 4; R44EY019785
• First Posted: Mar 12, 2012
• Last Update Posted: May 18, 2022
• Last Verified: Apr 1, 2022

• Keywords provided by Tissue Tech Inc.: Glaucoma Drainage Device, Tube Exposure, Amniotic Membrane
• Additional relevant MeSH terms: Glaucoma

Study Results

Participant Flow

Arm/Group Title	GDD & Amniotic Membrane Graft	GDD & Pericardial Graft
Arm/Group Description	After GDD implantation, amniotic membrane graft (AmnioGuard™, Bio-Tissue inc, Miami, FL) is used to cover the GDD tube. GDD: The surgery includes conjunctival incision, placement and securing the GDD plate in one quadrant, paracentesis and tube insertion into the anterior chamber, tube fixation to the episclera. Amniotic Membrane Graft: For subjects assigned to the treatment group, Amnioguard is used to cover the shunt tube. The conjunctiva is then closed.	After GDD implantation, a pericardial graft (Tutoplast®, IOP Inc, Costa Mesa, CA) is used to cover the GDD tube. GDD: The surgery includes conjunctival incision, placement and securing the GDD plate in one quadrant, paracentesis and tube insertion into the anterior chamber, tube fixation to the episclera. Pericardial Graft: For subjects assigned to the control group Tutoplast is used to cover the tube. The conjunctiva is then closed.
Period Title: Overall Study
STARTED	41	41
COMPLETED	41	40
NOT COMPLETED	0	1

Baseline Characteristics

Arm/Group Title	GDD & Amniotic Membrane Graft	GDD & Pericardial Graft	Total
Arm/Group Description	After GDD implantation, amniotic membrane graft (AmnioGuard™, Bio-Tissue inc, Miami, FL) is used to cover the GDD tube. GDD: The surgery includes conjunctival incision, placement and securing the GDD plate in one quadrant, paracentesis and tube insertion into the anterior chamber, tube fixation to the episclera. Amniotic Membrane Graft: For subjects assigned to the treatment group, Amnioguard is used to cover the shunt tube. The conjunctiva is then closed.	After GDD implantation, a pericardial graft (Tutoplast®, IOP Inc, Costa Mesa, CA) is used to cover the GDD tube. GDD: The surgery includes conjunctival incision, placement and securing the GDD plate in one quadrant, paracentesis and tube insertion into the anterior chamber, tube fixation to the episclera. Pericardial Graft: For subjects assigned to the control group Tutoplast is used to cover the tube. The conjunctiva is then closed.	Total of all reporting groups
Overall Participants	41	40	81
Age (yrs) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [yrs]	65.4 (13.6)	68.9 (12.3)	67 (13)
Sex: Female, Male (Count of Participants)
Female	22 53.7%	28 70%	50 61.7%
Male	19 46.3%	12 30%	31 38.3%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	4 10%	4 4.9%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	18 43.9%	10 25%	28 34.6%
White	23 56.1%	26 65%	49 60.5%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Tube Erosion
Description	Impending conjunctival erosion can be indicated by loss of conjunctival capillaries over the tube, usually 1 to 3 mm from the corneoscleral junction. Definitive tube exposure is accompanied by conjunctival tissue loss, graft melting.
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	GDD & Amniotic Membrane Graft	GDD & Pericardial Graft
Arm/Group Description	After GDD implantation, amniotic membrane graft (AmnioGuard™, Bio-Tissue inc, Miami, FL) is used to cover the GDD tube. GDD: The surgery includes conjunctival incision, placement and securing the GDD plate in one quadrant, paracentesis and tube insertion into the anterior chamber, tube fixation to the episclera. Amniotic Membrane Graft: For subjects assigned to the treatment group, Amnioguard is used to cover the shunt tube. The conjunctiva is then closed.	After GDD implantation, a pericardial graft (Tutoplast®, IOP Inc, Costa Mesa, CA) is used to cover the GDD tube. GDD: The surgery includes conjunctival incision, placement and securing the GDD plate in one quadrant, paracentesis and tube insertion into the anterior chamber, tube fixation to the episclera. Pericardial Graft: For subjects assigned to the control group Tutoplast is used to cover the tube. The conjunctiva is then closed.
Measure Participants	41	40
Count of Participants [Participants]	2 4.9%	11 27.5%

2. Secondary Outcome

Title	Number of Participants With Glaucoma Drainage Device Failure
Description	GDD Failure, based on reoperation to control the IOP, and also include the defined by the following criteria: (1) IOP ≥21 mm Hg or not reduced by 30% below baseline on two consecutive follow-up visits after 3 months. (2) IOP ≤5 mm Hg on two consecutive follow-up visits after 3 months. (3) Additional glaucoma surgery. (4) Loss of light perception vision.
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	GDD & Amniotic Membrane Graft	GDD & Pericardial Graft
Arm/Group Description	After GDD implantation, amniotic membrane graft (AmnioGuard™, Bio-Tissue inc, Miami, FL) is used to cover the GDD tube. GDD: The surgery includes conjunctival incision, placement and securing the GDD plate in one quadrant, paracentesis and tube insertion into the anterior chamber, tube fixation to the episclera. Amniotic Membrane Graft: For subjects assigned to the treatment group, Amnioguard is used to cover the shunt tube. The conjunctiva is then closed.	After GDD implantation, a pericardial graft (Tutoplast®, IOP Inc, Costa Mesa, CA) is used to cover the GDD tube. GDD: The surgery includes conjunctival incision, placement and securing the GDD plate in one quadrant, paracentesis and tube insertion into the anterior chamber, tube fixation to the episclera. Pericardial Graft: For subjects assigned to the control group Tutoplast is used to cover the tube. The conjunctiva is then closed.
Measure Participants	41	40
Count of Participants [Participants]	2 4.9%	2 5%

Adverse Events

Arm/Group Title	GDD & Amniotic Membrane Graft		GDD & Pericardial Graft
Arm/Group Description	After GDD implantation, amniotic membrane graft (AmnioGuard™, Bio-Tissue inc, Miami, FL) is used to cover the GDD tube. GDD: The surgery includes conjunctival incision, placement and securing the GDD plate in one quadrant, paracentesis and tube insertion into the anterior chamber, tube fixation to the episclera. Amniotic Membrane Graft: For subjects assigned to the treatment group, Amnioguard is used to cover the shunt tube. The conjunctiva is then closed.		After GDD implantation, a pericardial graft (Tutoplast®, IOP Inc, Costa Mesa, CA) is used to cover the GDD tube. GDD: The surgery includes conjunctival incision, placement and securing the GDD plate in one quadrant, paracentesis and tube insertion into the anterior chamber, tube fixation to the episclera. Pericardial Graft: For subjects assigned to the control group Tutoplast is used to cover the tube. The conjunctiva is then closed.
All Cause Mortality
	GDD & Amniotic Membrane Graft		GDD & Pericardial Graft
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	GDD & Amniotic Membrane Graft		GDD & Pericardial Graft
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/41 (0%)		0/41 (0%)
Other (Not Including Serious) Adverse Events
	GDD & Amniotic Membrane Graft		GDD & Pericardial Graft
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/41 (4.9%)		3/41 (7.3%)
Eye disorders
Corneal Edema	2/41 (4.9%)		3/41 (7.3%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.