AMCT: Ahmed Glaucoma Valve Surgery With Mitomycin-C

• Sponsor: University of California, San Francisco (Other)
• Overall Status: Completed
• CT.gov ID: NCT02805257
• Collaborator: Bascom Palmer Eye Institute (Other), University of North Carolina (Other), University of Colorado, Denver (Other), University of Maryland (Other), Zhongshan Ophthalmic Center, Sun Yat-sen University (Other), Asociación para Evitar la Ceguera en México (Other), Hospital Central Militar (Other), Shri Ganesh Vinayak Eye Hospital (Other)
• Enrollment: 119
• Locations: 4
• Arms: 2
• Actual Duration (Months): 45
• Patients Per Site: 29.8
• Patients Per Site Per Month: 0.7

Study Details

Study Description

Brief Summary

This study will determine the effectiveness of Mitomycin-C use in the glaucoma surgery Ahmed valve implantation. Approximately 100 patients will be enrolled, with half receiving the Mitomycin-C treatment and the other half receiving placebo treatment.

Condition or Disease	Intervention/Treatment	Phase
Glaucoma; Primary Open Angle Glaucoma; Secondary Glaucoma; Neovascular Glaucoma	Drug: Mitomycin-C; Other: Balanced Salt Solution; Procedure: Ahmed Glaucoma Valve Implant	Phase 2

Detailed Description

Glaucoma is a leading cause irreversible blindness worldwide. Glaucoma valve surgeries such as Ahmed valve implantation, which are conventional surgeries performed to control intraocular pressure in eyes, are sometimes associated with complications due to fibrosis. Mitomycin-C is a commonly used antifibrotic agent used in glaucoma surgeries. This study will evaluate the effectiveness of Mitomycin-C injections intraoperatively and postoperatively.

Study Design

• Study Type: Interventional
• Actual Enrollment: 119 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Ahmed Glaucoma Valve Surgery With Mitomycin-C
• Actual Study Start Date: Jun 1, 2016
• Actual Primary Completion Date: Mar 1, 2020
• Actual Study Completion Date: Mar 1, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Mitomycin-C 0.1 ml of Mitomycin-C 0.4mg/ml injection intraoperatively and twice postoperatively.	Drug: Mitomycin-C; Intraoperative and postoperative injections of mitomycin-c/Mitosol; Other Names: Mitosol ; Procedure: Ahmed Glaucoma Valve Implant; Implantation of Ahmed Valve in study eye
Placebo Comparator: Balanced Salt Solution (BSS) 0.1ml Balanced Salt Solution injection intraoperatively and twice postoperatively.	Other: Balanced Salt Solution; Intraoperative and postoperative injections of BSS; Other Names: BSS ; Procedure: Ahmed Glaucoma Valve Implant; Implantation of Ahmed Valve in study eye

Outcome Measures

Primary Outcome Measures

1. Intraocular Pressure After Surgery [1 year]

   Goldmann applanation tonometry was used to measure intraocular pressure (IOP) at their one-year after surgery visit, however, for patients with irregular corneal astigmatism, corneal scarring, or corneal edema, which affect accurate measurement, pneumatonometer or Tonopen (Reichert Technologies, Depew, NY) was used. Two consecutive measurements were taken for the study eye. If the 2 measurements differ by 1 mm Hg or less, the IOP for the study eye was the average of the 2 readings. If the 2 measurements differ by 2 mm Hg or more, a third measurement was taken, and the IOP for the study eye was the median of the 3 readings. Efforts were made to schedule follow-up visits at similar time of the day to minimize the effect of diurnal IOP fluctuation. The average IOP and its standard deviation for each arm were calculated based on the individual IOP result obtained using the method described above.

Secondary Outcome Measures

1. Intraocular Pressure After Surgery [6 months]

   Goldmann applanation tonometry was used to measure intraocular pressure (IOP) at their six-month after surgery visit, however, for patients with irregular corneal astigmatism, corneal scarring, or corneal edema, which affect accurate measurement, pneumatonometer or Tonopen (Reichert Technologies, Depew, NY) was used. Two consecutive measurements were taken for the study eye. If the 2 measurements differ by 2 mm Hg or more, a third measurement was taken, and the IOP for the study eye was the median of the 3 readings. Efforts were made to schedule follow-up visits at similar time of the day to minimize the effect of diurnal IOP fluctuation. The average IOP and its standard deviation for each arm were calculated based on the individual IOP result obtained using the method described above.

2. Number of Medications Postoperatively [6 months]

   Counted the number of glaucoma drops at six-month after surgery visit. Glaucoma drops are characterized as topical medication used to help lower intraocular pressure.

3. Visual Acuity [6 months]

   The Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity is tested at the six-month after surgery visit. The ETDRS Letter Score is calculated by the number of letters accurately identified at a certain distance, with the range of score being 0-100. An ETDRS letter score of 85 is considered normal vision (equivalent to visual acuity of 20/20), letter scores from 70-84 and 86-100 are considered minimal vision loss and near-normal vision, letter scores from 40-60 are considered moderate visual impairment, and letter scores 0-40 are considered severe visual impairment to total blindness.

4. Number of Medications Postoperatively [1 year]

   Counted the number of glaucoma drops at one-year after surgery visit. Glaucoma drops are characterized as topical medication used to help lower intraocular pressure.

5. Number of Participants With Intraoperative Complications [Day of Surgery]

   Intraoperative complications are characterized as problems that happened during surgery but which were not intended. All complications during surgery were listed and analyzed.

6. Visual Acuity [1 year]

   The Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity is tested at the one-year after surgery visit. The ETDRS Letter Score is calculated by the number of letters accurately identified at a certain distance, with the range of score being 0-100. An ETDRS letter score of 85 is considered normal vision (equivalent to visual acuity of 20/20), letter scores from 70-84 and 86-100 are considered minimal vision loss and near-normal vision, letter scores from 40-60 are considered moderate visual impairment, and letter scores 0-40 are considered severe visual impairment to total blindness.

7. Number of Participants With Postoperative Complications [1 Year]

   Postoperative complications are characterized as problems that happened after surgery but which were not intended. All complications up to the one-year after surgery visit observed were listed and analyzed.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 85 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Inadequately controlled glaucoma on maximum tolerated medical therapy with intraocular pressure (IOP) greater than or equal to 18 mm Hg.

• Ahmed Glaucoma Valve (AGV) implantation as the planned surgical procedure.

• For patients in whom 2 eyes are eligible for enrollment, only the first eligible eye to be implanted is enrolled.

Exclusion Criteria:

• Unwilling or unable to give consent, unwilling to accept randomization, or unable to return for scheduled protocol visits.

• Pregnant or nursing women.

• Previous cyclodestruction or glaucoma drainage device (GDD) surgery.

• Patients with nanophthalmos.

• Patients with Sturge-Weber syndrome or other conditions associated with elevated episcleral venous pressure.

• No light perception vision.

• VA <20/200 in non-study eye.

• Need for glaucoma surgery combined with other ocular procedures (i.e. cataract extraction, penetrating keratoplasty, or retinal surgery) or anticipated need for additional ocular surgery.

• Previous scleral buckling procedure or silicone oil present.

• Uveitic glaucoma.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of California, San Francisco	San Francisco	California	United States	94121
2	Zhongshan Ophthalmic Center	Guangzhou	Guangdong	China
3	Shri Ganesh Vinayak Eye Hospital	Raipur	Chhattisgarh	India
4	Asociación para Evitar la Ceguera en México (APEC)	Mexico City		Mexico

Sponsors and Collaborators

• University of California, San Francisco
• Bascom Palmer Eye Institute
• University of North Carolina
• University of Colorado, Denver
• University of Maryland
• Zhongshan Ophthalmic Center, Sun Yat-sen University
• Asociación para Evitar la Ceguera en México
• Hospital Central Militar
• Shri Ganesh Vinayak Eye Hospital

Investigators

• Principal Investigator: Ying Han, MD, PhD, University of California, San Francisco

Study Documents (Full-Text)

• Study Protocol - Dec 12, 2017
• Statistical Analysis Plan - Dec 12, 2017

More Information

Publications

None provided.

• Responsible Party: University of California, San Francisco
• ClinicalTrials.gov Identifier: NCT02805257
• Other Study ID Numbers: IRB#16-18935
• First Posted: Jun 17, 2016
• Last Update Posted: May 31, 2022
• Last Verified: May 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No
• Additional relevant MeSH terms: Glaucoma; Glaucoma, Open-Angle; Glaucoma, Neovascular; Mitomycins; Mitomycin

Study Results

Participant Flow

Arm/Group Title	Mitomycin-C	Balanced Salt Solution (BSS)
Arm/Group Description	0.1 ml of Mitomycin-C 0.4mg/ml injection intraoperatively and twice postoperatively. Mitomycin-C: Intraoperative and postoperative injections of mitomycin-c/Mitosol	0.1ml Balanced Salt Solution injection intraoperatively and twice postoperatively. Balanced Salt Solution: Intraoperative and postoperative injections of BSS
Period Title: Overall Study
STARTED	60	59
COMPLETED	53	52
NOT COMPLETED	7	7

Baseline Characteristics

Arm/Group Title	Mitomycin-C	Balanced Salt Solution (BSS)	Total
Arm/Group Description	0.1 ml of Mitomycin-C 0.4mg/ml injection intraoperatively and twice postoperatively. Mitomycin-C: Intraoperative and postoperative injections of mitomycin-c/Mitosol	0.1ml Balanced Salt Solution injection intraoperatively and twice postoperatively. Balanced Salt Solution: Intraoperative and postoperative injections of BSS	Total of all reporting groups
Overall Participants	60	59	119
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	52.7 (13.4)	58.76 (14.8)	55.6 (14.4)
Sex: Female, Male (Count of Participants)
Female	29 48.3%	25 42.4%	54 45.4%
Male	31 51.7%	34 57.6%	65 54.6%
Race/Ethnicity, Customized (Count of Participants)
Chinese	9 15%	11 18.6%	20 16.8%
Mexican	51 85%	48 81.4%	99 83.2%
Region of Enrollment (participants) [Number]
China	9 15%	11 18.6%	20 16.8%
Mexico	51 85%	48 81.4%	99 83.2%

Outcome Measures

1. Primary Outcome

Title	Intraocular Pressure After Surgery
Description	Goldmann applanation tonometry was used to measure intraocular pressure (IOP) at their one-year after surgery visit, however, for patients with irregular corneal astigmatism, corneal scarring, or corneal edema, which affect accurate measurement, pneumatonometer or Tonopen (Reichert Technologies, Depew, NY) was used. Two consecutive measurements were taken for the study eye. If the 2 measurements differ by 1 mm Hg or less, the IOP for the study eye was the average of the 2 readings. If the 2 measurements differ by 2 mm Hg or more, a third measurement was taken, and the IOP for the study eye was the median of the 3 readings. Efforts were made to schedule follow-up visits at similar time of the day to minimize the effect of diurnal IOP fluctuation. The average IOP and its standard deviation for each arm were calculated based on the individual IOP result obtained using the method described above.
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Mitomycin-C	Balanced Salt Solution (BSS)
Arm/Group Description	0.1 ml of Mitomycin-C 0.4mg/ml injection intraoperatively and twice postoperatively. Mitomycin-C: Intraoperative and postoperative injections of mitomycin-c/Mitosol	0.1ml Balanced Salt Solution injection intraoperatively and twice postoperatively. Balanced Salt Solution: Intraoperative and postoperative injections of BSS
Measure Participants	53	52
Mean (Standard Deviation) [mmHg]	13.1 (6.3)	16.2 (6.2)

2. Secondary Outcome

Title	Intraocular Pressure After Surgery
Description	Goldmann applanation tonometry was used to measure intraocular pressure (IOP) at their six-month after surgery visit, however, for patients with irregular corneal astigmatism, corneal scarring, or corneal edema, which affect accurate measurement, pneumatonometer or Tonopen (Reichert Technologies, Depew, NY) was used. Two consecutive measurements were taken for the study eye. If the 2 measurements differ by 2 mm Hg or more, a third measurement was taken, and the IOP for the study eye was the median of the 3 readings. Efforts were made to schedule follow-up visits at similar time of the day to minimize the effect of diurnal IOP fluctuation. The average IOP and its standard deviation for each arm were calculated based on the individual IOP result obtained using the method described above.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Mitomycin-C	Balanced Salt Solution (BSS)
Arm/Group Description	0.1 ml of Mitomycin-C 0.4mg/ml injection intraoperatively and twice postoperatively. Mitomycin-C: Intraoperative and postoperative injections of mitomycin-c/Mitosol	0.1ml Balanced Salt Solution injection intraoperatively and twice postoperatively. Balanced Salt Solution: Intraoperative and postoperative injections of BSS
Measure Participants	53	52
Mean (Standard Deviation) [mmHg]	14.6 (8.0)	16.1 (6.9)

3. Secondary Outcome

Title	Number of Medications Postoperatively
Description	Counted the number of glaucoma drops at six-month after surgery visit. Glaucoma drops are characterized as topical medication used to help lower intraocular pressure.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Mitomycin-C	Balanced Salt Solution (BSS)
Arm/Group Description	0.1 ml of Mitomycin-C 0.4mg/ml injection intraoperatively and twice postoperatively. Mitomycin-C: Intraoperative and postoperative injections of mitomycin-c/Mitosol	0.1ml Balanced Salt Solution injection intraoperatively and twice postoperatively. Balanced Salt Solution: Intraoperative and postoperative injections of BSS
Measure Participants	53	52
Mean (Standard Deviation) [glaucoma drops]	1.2 (0.4)	1.6 (0.3)

4. Secondary Outcome

Title	Visual Acuity
Description	The Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity is tested at the six-month after surgery visit. The ETDRS Letter Score is calculated by the number of letters accurately identified at a certain distance, with the range of score being 0-100. An ETDRS letter score of 85 is considered normal vision (equivalent to visual acuity of 20/20), letter scores from 70-84 and 86-100 are considered minimal vision loss and near-normal vision, letter scores from 40-60 are considered moderate visual impairment, and letter scores 0-40 are considered severe visual impairment to total blindness.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

Unable to report visual acuity data at six months for one Mitomycin-C patient and six Balanced Salt Solution patients due to missing data entry.

Arm/Group Title	Mitomycin-C	Balanced Salt Solution (BSS)
Arm/Group Description	0.1 ml of Mitomycin-C 0.4mg/ml injection intraoperatively and twice postoperatively. Mitomycin-C: Intraoperative and postoperative injections of mitomycin-c/Mitosol	0.1ml Balanced Salt Solution injection intraoperatively and twice postoperatively. Balanced Salt Solution: Intraoperative and postoperative injections of BSS
Measure Participants	52	46
Mean (Standard Deviation) [score on a scale]	12.81 (6.98)	15.33 (6.84)

5. Secondary Outcome

Title	Number of Medications Postoperatively
Description	Counted the number of glaucoma drops at one-year after surgery visit. Glaucoma drops are characterized as topical medication used to help lower intraocular pressure.
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Mitomycin-C	Balanced Salt Solution (BSS)
Arm/Group Description	0.1 ml of Mitomycin-C 0.4mg/ml injection intraoperatively and twice postoperatively. Mitomycin-C: Intraoperative and postoperative injections of mitomycin-c/Mitosol	0.1ml Balanced Salt Solution injection intraoperatively and twice postoperatively. Balanced Salt Solution: Intraoperative and postoperative injections of BSS
Measure Participants	53	52
Mean (Standard Deviation) [glaucoma drops]	1.2 (0.3)	1.6 (0.4)

6. Secondary Outcome

Title	Number of Participants With Intraoperative Complications
Description	Intraoperative complications are characterized as problems that happened during surgery but which were not intended. All complications during surgery were listed and analyzed.
Time Frame	Day of Surgery

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Mitomycin-C	Balanced Salt Solution (BSS)
Arm/Group Description	0.1 ml of Mitomycin-C 0.4mg/ml injection intraoperatively and twice postoperatively. Mitomycin-C: Intraoperative and postoperative injections of mitomycin-c/Mitosol	0.1ml Balanced Salt Solution injection intraoperatively and twice postoperatively. Balanced Salt Solution: Intraoperative and postoperative injections of BSS
Measure Participants	53	52
Hyphema	3 5%	5 8.5%
Suprachoroidal Hemorrhage	0 0%	0 0%
Other	0 0%	1 1.7%

7. Secondary Outcome

Title	Visual Acuity
Description	The Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity is tested at the one-year after surgery visit. The ETDRS Letter Score is calculated by the number of letters accurately identified at a certain distance, with the range of score being 0-100. An ETDRS letter score of 85 is considered normal vision (equivalent to visual acuity of 20/20), letter scores from 70-84 and 86-100 are considered minimal vision loss and near-normal vision, letter scores from 40-60 are considered moderate visual impairment, and letter scores 0-40 are considered severe visual impairment to total blindness.
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

Unable to report visual acuity data at one year for three Mitomycin-C patients and eight Balanced Salt Solution patients due to missing data entry.

Arm/Group Title	Mitomycin-C	Balanced Salt Solution (BSS)
Arm/Group Description	0.1 ml of Mitomycin-C 0.4mg/ml injection intraoperatively and twice postoperatively. Mitomycin-C: Intraoperative and postoperative injections of mitomycin-c/Mitosol	0.1ml Balanced Salt Solution injection intraoperatively and twice postoperatively. Balanced Salt Solution: Intraoperative and postoperative injections of BSS
Measure Participants	50	44
Mean (Standard Deviation) [score on a scale]	12.4 (7.33)	16 (7.78)

8. Secondary Outcome

Title	Number of Participants With Postoperative Complications
Description	Postoperative complications are characterized as problems that happened after surgery but which were not intended. All complications up to the one-year after surgery visit observed were listed and analyzed.
Time Frame	1 Year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Mitomycin-C	Balanced Salt Solution (BSS)
Arm/Group Description	0.1 ml of Mitomycin-C 0.4mg/ml injection intraoperatively and twice postoperatively. Mitomycin-C: Intraoperative and postoperative injections of mitomycin-c/Mitosol	0.1ml Balanced Salt Solution injection intraoperatively and twice postoperatively. Balanced Salt Solution: Intraoperative and postoperative injections of BSS
Measure Participants	53	52
Tube occlusion	3 5%	1 1.7%
Choroidal effusion	2 3.3%	1 1.7%
Suprachoroidal hemorrhage	1 1.7%	2 3.4%
Hyphema	6 10%	7 11.9%
Vitreous hemorrhage	1 1.7%	2 3.4%
Shallow Anterior Chamber	9 15%	9 15.3%
Corneal edema	1 1.7%	0 0%
Endophthalmitis, cystoid macular edema, hypotony maculopathy, tube-K touch, tube erosion, diplopia	2 3.3%	0 0%
Other	8 13.3%	6 10.2%

Adverse Events

Time Frame	Over 1 Year
Adverse Event Reporting Description	In our study protocol, we defined Serious Adverse Events as the following "A SAE is any adverse event that results in any of the following outcomes: death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, or a persistent or significant disability/incapacity."
Arm/Group Title	Mitomycin-C		Balanced Salt Solution (BSS)
Arm/Group Description	0.1 ml of Mitomycin-C 0.4mg/ml injection intraoperatively and twice postoperatively. Mitomycin-C: Intraoperative and postoperative injections of mitomycin-c/Mitosol		0.1ml Balanced Salt Solution injection intraoperatively and twice postoperatively. Balanced Salt Solution: Intraoperative and postoperative injections of BSS
All Cause Mortality
	Mitomycin-C		Balanced Salt Solution (BSS)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/53 (0%)		1/52 (1.9%)
Serious Adverse Events
	Mitomycin-C		Balanced Salt Solution (BSS)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/53 (0%)		0/52 (0%)
Other (Not Including Serious) Adverse Events
	Mitomycin-C		Balanced Salt Solution (BSS)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	23/53 (43.4%)		21/52 (40.4%)
Eye disorders
Tube Occlusion	3/53 (5.7%)		1/52 (1.9%)
Choroidal Effusion	2/53 (3.8%)		1/52 (1.9%)
Suprachoroidal hemorrhage	1/53 (1.9%)		2/52 (3.8%)
Hyphema	6/53 (11.3%)		7/52 (13.5%)
Vitreous hemorrhage	1/53 (1.9%)		2/52 (3.8%)
Shallow Anterior Chamber	9/53 (17%)		9/52 (17.3%)
Corneal edema	1/53 (1.9%)		0/52 (0%)
Other	8/53 (15.1%)		6/52 (11.5%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE 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.