PROMISE: Prevention of Macular Edema In Patients With Diabetic Retinopathy Undergoing Cataract Surgery

• Sponsor: Rishi Singh (Other)
• Overall Status: Completed
• CT.gov ID: NCT01988246
• Collaborator: Regeneron Pharmaceuticals (Industry)
• Enrollment: 30
• Location: 1
• Arms: 2
• Duration (Months): 73.4
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

To determine the safety and efficacy of intravitreal Aflibercept (Eylea) injection in patients with diabetic retinopathy in the prevention of macular edema following cataract surgery.

Condition or Disease	Intervention/Treatment	Phase
Diabetic Retinopathy	Drug: Aflibercept; Drug: Sham	Phase 1/Phase 2

Detailed Description

Diabetic retinopathy patients who are at risk of developing macular edema (defined as ≥ 30 % increase from pre-operative baseline in central subfield macular thickness) within 90 days following cataract surgery. Diabetic patients are defined as those who have either Type 1 or Type 2 diabetes. The patients must have either mild, moderate, or severe non proliferative retinopathy or treated proliferative retinopathy. Patients must be 18 years of age and older, of any race and either sex, requiring cataract extraction with planned implantation of a posterior chamber intraocular lens into the lens capsule.

Study Design

• Study Type: Interventional
• Actual Enrollment: 30 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Participant)
• Primary Purpose: Prevention
• Official Title: Prevention of Macular Edema In Patients With Diabetic Retinopathy Undergoing Cataract Surgery
• Study Start Date: Dec 1, 2013
• Actual Primary Completion Date: Apr 25, 2018
• Actual Study Completion Date: Jan 14, 2020

Arms and Interventions

Arm	Intervention/Treatment
Sham Comparator: Sham Injection Patients will be sequentially randomized to treatment with a "sham" injection at the time of surgery. The sham injection is accomplished by pressing an empty syringe against the eye wall without penetration. This will be administered post cataract excision by the Prinicipal Investigator. The patient will be masked as to which Arm they are assigned.	Drug: Sham; Sham injection. No actual injection. No medication is used.
Active Comparator: Intravitreal Aflibercept Injection Patients will be sequentially randomized to treatment with Aflibercept 2 mg via intravitreal injection (0.05 mL or 50 microliters) at the time of surgery. This will be administered post cataract excision by the Principal Investigator. The patient will be masked as to which Arm they are assigned.	Drug: Aflibercept; Patients will be assigned to treatment with 2 mg intravitreal Aflibercept injection (0.05 mL or 50 microliters) administered at the time of surgery (post cataract excision) or sham injection.; Other Names: Eylea

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Ocular and Non-Ocular Adverse Events [Day 90]

   Number of participants with ocular and non-ocular adverse events (AEs) in both treatment arms.

Secondary Outcome Measures

1. Change From Baseline in Best-Corrected Visual Acuity (BCVA) Score [Day 90]

   Change from baseline in best-corrected visual acuity (BCVA) score and BCVA score at Day 90 as measured by ETDRS (early treatment diabetic retinopathy study) There were no sub scales used. These are common methods for ophthalmology studies to report their findings. The scale provided is the Electronic-Early Treatment in Diabetic Retinopathy Scale (E-ETDRS) best corrected visual acuity scale. Values that are higher are considered better and values that are lower are considered worse. Minimum E-ETDRS was 24 E-ETDRS letters and maximum E-ETDRS was 80 E-ETDRS letters.

Other Outcome Measures

1. Change From Baseline in Retinal Thickness [Day 90]

   The change in macular edema as measured by SD-OCT (spectral domain ocular coherence tomography)at 90 days

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• A patient must meet the following criteria to be eligible for inclusion in the study:

1. Must be 18 years of age and older, of any race and either sex, who have a cataract, and are planning to undergo cataract extraction by phacoemulsification with the implantation of a posterior chamber intraocular lens into the lens capsule

2. History of Type I or Type II diabetes

3. NPDR: non-proliferative diabetic retinopathy (mild, moderate, or severe) or inactive proliferative disease in the study eye as defined by the International Clinical Diabetic Retinopathy Disease Severity Scale

4. Willing and able to comply with clinic visits and study-related procedures

5. Patients must be able to understand and sign an informed consent that has been approved by an Institutional Review Board (IRB)

6. Central subfield macular thickness ≤ 320 μm in the study eye prior to cataract surgery as determined by SD-OCT and confirmed by the reading center

7. Absence of clinically significant macular edema (CSME) in the study eye as detected by clinical exam

8. Patients must have visual acuity of 20/20-20/200

Exclusion Criteria:

A patient who meets any of the following criteria will be excluded from the study:

1. Signs of vitreomacular traction or epiretinal membrane in the study eye as detected by reading center or investigator

2. Current or previous ocular disease in the study eye that in the opinion of the investigator may confound assessment of the macula, the retina, or central vision other that diabetic retinopathy

3. Active proliferative diabetic retinopathy in the study eye

4. Planned multiple procedures for study eye during the cataract/IOL implantation surgery (e.g., trabeculectomy, corneal transplant)

5. Patients who have received corneal transplants in the study eye

6. Patients with current or history of chronic or recurrent ocular infections or inflammation in the study eye

7. Patients with a visually nonfunctional fellow eye based upon the assessment by the investigator

8. Patients who are immunocompromised (e.g., patients receiving chemotherapy irradiation therapy, patients with AIDS, leukemia, or cachexia) or patients receiving dialysis

9. Use of medications known to affect the macula, including hydroxychloroquinine (Plaquenil) and phenothiozines (e.g., thioridazine [Mellaril], chloropromazine [Thorazine]) or supplemental niacin ≥3 grams/day

10. Use of systemic steroids, NSAIDS (non-steroidal anti-inflammatory drugs), anti-VEGF agents within 7 days prior to surgery (through study exit). Daily doses of aspirin, up to 325 mg, will be permitted.

11. Use of topical ocular NSAIDS and steroids, in the study eye, within 7 days prior to surgery

12. Treatment with intraocular or periocular steroids in the study eye within 3 months prior to surgery

13. Focal photocoagulation for the treatment of diabetic macular edema in the study eye within 6 months of the pre-operative baseline visit (Note: peripheral retina treatment for retinal tear or lattice degeneration is permitted)

14. Intravitreal anti-VEGF (vascular endothelial growth factor) treatment in the study eye within 6 months of the pre-operative baseline visit

15. Patients with a known hypersensitivity to NSAIDs or steroids or any component of the study medication.

16. Use of a topical ophthalmic prostaglandin (e.g., TRAVATAN, XALATAN) within 4 days of surgery through study exit

17. Any concurrent intraocular condition in the study eye that, in the opinion of the investigator, could require either medical or surgical intervention during the 90 day study period.

18. Any concurrent ocular condition in the study eye which, in the opinion of the investigator, could either increase the risk to the patient beyond what is to be expected from standard procedures of intraocular injection, or which otherwise may interfere with the injection procedure or with evaluation of efficacy or safety.

19. Pregnant or breast-feeding women -

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Cole Eye Institute, Cleveland Clinic	Cleveland	Ohio	United States	44195

Sponsors and Collaborators

• Rishi Singh
• Regeneron Pharmaceuticals

Investigators

• Principal Investigator: Rishi Singh, M.D., Cole Eye Institute, Cleveland Clinic

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jul 25, 2018
• Informed Consent Form - May 8, 2015

More Information

Publications

None provided.

• Responsible Party: Rishi Singh, staff surgeon / Sponsor-Investigator, The Cleveland Clinic
• ClinicalTrials.gov Identifier: NCT01988246
• Other Study ID Numbers: PROMISE Trial
• First Posted: Nov 20, 2013
• Last Update Posted: May 22, 2020
• Last Verified: May 1, 2020

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Keywords provided by Rishi Singh, staff surgeon / Sponsor-Investigator, The Cleveland Clinic: Diabetes; Diabetic Retinopathy
• Additional relevant MeSH terms: Cataract; Macular Edema; Retinal Diseases; Diabetic Retinopathy; Aflibercept

Study Results

Participant Flow

Arm/Group Title	Sham Injection	Intravitreal Aflibercept Injection
Arm/Group Description	Patients will be sequentially randomized to treatment with a "sham" injection at the time of surgery. The sham injection is accomplished by pressing an empty syringe against the eye wall without penetration. This will be administered post cataract excision by the Prinicipal Investigator. The patient will be masked as to which Arm they are assigned. Sham: Sham injection. No actual injection. No medication is used.	Patients will be sequentially randomized to treatment with Aflibercept 2 mg via intravitreal injection (0.05 mL or 50 microliters) at the time of surgery. This will be administered post cataract excision by the Principal Investigator. The patient will be masked as to which Arm they are assigned. Aflibercept: Patients will be assigned to treatment with 2 mg intravitreal Aflibercept injection (0.05 mL or 50 microliters) administered at the time of surgery (post cataract excision) or sham injection.
Period Title: Overall Study
STARTED	15	15
COMPLETED	14	15
NOT COMPLETED	1	0

Baseline Characteristics

Arm/Group Title	Sham Injection	Intravitreal Aflibercept Injection	Total
Arm/Group Description	Patients will be sequentially randomized to treatment with a "sham" injection at the time of surgery. The sham injection is accomplished by pressing an empty syringe against the eye wall without penetration. This will be administered post cataract excision by the Prinicipal Investigator. The patient will be masked as to which Arm they are assigned. Sham: Sham injection. No actual injection. No medication is used.	Patients will be sequentially randomized to treatment with Aflibercept 2 mg via intravitreal injection (0.05 mL or 50 microliters) at the time of surgery. This will be administered post cataract excision by the Principal Investigator. The patient will be masked as to which Arm they are assigned. Aflibercept: Patients will be assigned to treatment with 2 mg intravitreal Aflibercept injection (0.05 mL or 50 microliters) administered at the time of surgery (post cataract excision) or sham injection.	Total of all reporting groups
Overall Participants	15	15	30
Age, Customized (years) [Mean (Full Range) ]
Mean (Full Range) [years]	66	66	66
Sex: Female, Male (Count of Participants)
Female	10 66.7%	6 40%	16 53.3%
Male	5 33.3%	9 60%	14 46.7%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	2 13.3%	3 20%	5 16.7%
Not Hispanic or Latino	13 86.7%	12 80%	25 83.3%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	6 40%	3 20%	9 30%
White	6 40%	10 66.7%	16 53.3%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	3 20%	2 13.3%	5 16.7%
Region of Enrollment (participants) [Number]
United States	15 100%	15 100%	30 100%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Ocular and Non-Ocular Adverse Events
Description	Number of participants with ocular and non-ocular adverse events (AEs) in both treatment arms.
Time Frame	Day 90

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Sham Injection	Intravitreal Aflibercept Injection
Arm/Group Description	Patients will be sequentially randomized to treatment with a "sham" injection at the time of surgery. The sham injection is accomplished by pressing an empty syringe against the eye wall without penetration. This will be administered post cataract excision by the Prinicipal Investigator. The patient will be masked as to which Arm they are assigned. Sham: Sham injection. No actual injection. No medication is used.	Patients will be sequentially randomized to treatment with Aflibercept 2 mg via intravitreal injection (0.05 mL or 50 microliters) at the time of surgery. This will be administered post cataract excision by the Principal Investigator. The patient will be masked as to which Arm they are assigned. Aflibercept: Patients will be assigned to treatment with 2 mg intravitreal Aflibercept injection (0.05 mL or 50 microliters) administered at the time of surgery (post cataract excision) or sham injection.
Measure Participants	15	15
At least 1 Ocular Adverse Event	11 73.3%	10 66.7%
At least 1 Non-Ocular Adverse Event	5 33.3%	3 20%

2. Secondary Outcome

Title	Change From Baseline in Best-Corrected Visual Acuity (BCVA) Score
Description	Change from baseline in best-corrected visual acuity (BCVA) score and BCVA score at Day 90 as measured by ETDRS (early treatment diabetic retinopathy study) There were no sub scales used. These are common methods for ophthalmology studies to report their findings. The scale provided is the Electronic-Early Treatment in Diabetic Retinopathy Scale (E-ETDRS) best corrected visual acuity scale. Values that are higher are considered better and values that are lower are considered worse. Minimum E-ETDRS was 24 E-ETDRS letters and maximum E-ETDRS was 80 E-ETDRS letters.
Time Frame	Day 90

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Sham Injection	Intravitreal Aflibercept Injection
Arm/Group Description	Patients will be sequentially randomized to treatment with a "sham" injection at the time of surgery. The sham injection is accomplished by pressing an empty syringe against the eye wall without penetration. This will be administered post cataract excision by the Prinicipal Investigator. The patient will be masked as to which Arm they are assigned. Sham: Sham injection. No actual injection. No medication is used.	Patients will be sequentially randomized to treatment with Aflibercept 2 mg via intravitreal injection (0.05 mL or 50 microliters) at the time of surgery. This will be administered post cataract excision by the Principal Investigator. The patient will be masked as to which Arm they are assigned. Aflibercept: Patients will be assigned to treatment with 2 mg intravitreal Aflibercept injection (0.05 mL or 50 microliters) administered at the time of surgery (post cataract excision) or sham injection.
Measure Participants	15	15
Mean (95% Confidence Interval) [Number of Letters Read Correctly]	8.52	9.88

3. Other Pre-specified Outcome

Title	Change From Baseline in Retinal Thickness
Description	The change in macular edema as measured by SD-OCT (spectral domain ocular coherence tomography)at 90 days
Time Frame	Day 90

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Sham Injection	Intravitreal Aflibercept Injection
Arm/Group Description	Patients will be sequentially randomized to treatment with a "sham" injection at the time of surgery. The sham injection is accomplished by pressing an empty syringe against the eye wall without penetration. This will be administered post cataract excision by the Prinicipal Investigator. The patient will be masked as to which Arm they are assigned. Sham: Sham injection. No actual injection. No medication is used.	Patients will be sequentially randomized to treatment with Aflibercept 2 mg via intravitreal injection (0.05 mL or 50 microliters) at the time of surgery. This will be administered post cataract excision by the Principal Investigator. The patient will be masked as to which Arm they are assigned. Aflibercept: Patients will be assigned to treatment with 2 mg intravitreal Aflibercept injection (0.05 mL or 50 microliters) administered at the time of surgery (post cataract excision) or sham injection.
Measure Participants	15	15
Mean (95% Confidence Interval) [Microns]	50.32	18.48

Adverse Events

Time Frame	Up to 90 days following each surgery
Arm/Group Title	Sham Injection		Intravitreal Aflibercept Injection
Arm/Group Description	Patients will be sequentially randomized to treatment with a "sham" injection at the time of surgery. The sham injection is accomplished by pressing an empty syringe against the eye wall without penetration. This will be administered post cataract excision by the Prinicipal Investigator. The patient will be masked as to which Arm they are assigned. Sham: Sham injection. No actual injection. No medication is used.		Patients will be sequentially randomized to treatment with Aflibercept 2 mg via intravitreal injection (0.05 mL or 50 microliters) at the time of surgery. This will be administered post cataract excision by the Principal Investigator. The patient will be masked as to which Arm they are assigned. Aflibercept: Patients will be assigned to treatment with 2 mg intravitreal Aflibercept injection (0.05 mL or 50 microliters) administered at the time of surgery (post cataract excision) or sham injection.
All Cause Mortality
	Sham Injection		Intravitreal Aflibercept Injection
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/15 (0%)		0/15 (0%)
Serious Adverse Events
	Sham Injection		Intravitreal Aflibercept Injection
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/15 (13.3%)		3/15 (20%)
Eye disorders
Paracentesis	0/15 (0%)		2/15 (13.3%)
Gastrointestinal disorders
Cough/Vomiting	0/15 (0%)		1/15 (6.7%)
Skin and subcutaneous tissue disorders
Rash and Swelling on Limbs	2/15 (13.3%)		0/15 (0%)
Other (Not Including Serious) Adverse Events
	Sham Injection		Intravitreal Aflibercept Injection
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	14/15 (93.3%)		10/15 (66.7%)
Eye disorders
Foreign Body Sensation	3/15 (20%)		3/15 (20%)
Corneal Edema	0/15 (0%)		1/15 (6.7%)
Eye Irritation/Pain	2/15 (13.3%)		2/15 (13.3%)
Eye Itching	1/15 (6.7%)		2/15 (13.3%)
Lacrimation Increased	1/15 (6.7%)		1/15 (6.7%)
Blurred Vision	4/15 (26.7%)		2/15 (13.3%)
Photophobia	3/15 (20%)		0/15 (0%)
Floaters	4/15 (26.7%)		2/15 (13.3%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.