CENTERA: Evaluation of a Treat and Extend Regimen of Intravitreal Aflibercept for Macular Edema Secondary to CRVO

• Sponsor: Bayer (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02800642
• Collaborator: (none)
• Enrollment: 162
• Locations: 42
• Arm: 1
• Actual Duration (Months): 37.7
• Patients Per Site: 3.9
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

Central retinal vein occlusion (CRVO) occurs when the main blood vessel that transports blood away from the retina (the very back portion of the eye) becomes blocked, causing the leakage of fluid into the retina and thereby causing a swelling of the macula (the portion of the retina responsible for fine vision). This swelling is called macular edema. When the macula swells with fluid, central vision becomes blurry. The study drug aflibercept has been shown to reduce the amount of fluid and blood leaked into the retina. It can help to stabilize, and in many cases, improve the vision loss related to CRVO. Aflibercept has been approved for the treatment of macular edema secondary to CRVO in the United States (US), European Union (EU), Japan, and other countries.

The study was considered research because, although the study drug was already on the market for macular edema secondary to CRVO, there were no studies available that addressed the questions of what were useful intervals for treating and assessing patients, how did they differ among patients, and how were criteria applied for retreatment. The purpose of this study was to evaluate the effectiveness, treatment interval, and safety of the treatment regimen (pattern for administering treatment) in subjects with macular edema secondary to CRVO. In addition, this study explored new imaging methods for assessing the affected eye.

Condition or Disease	Intervention/Treatment	Phase
Central Retinal Vein Occlusion	Drug: Aflibercept (Eylea, BAY86-5321)	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 162 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Multi-center, Single-arm, Interventional Phase 4 Study to Evaluate a Treat and Extend Regimen of Intravitreal Aflibercept for Treatment of Macular Edema Secondary to Central Retinal Vein Occlusion
• Actual Study Start Date: Jun 10, 2016
• Actual Primary Completion Date: Jul 31, 2019
• Actual Study Completion Date: Jul 31, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Intravitreal (IVT) aflibercept Participants with macular edema secondary to CRVO were treated with the study drug intravitreal aflibercept	Drug: Aflibercept (Eylea, BAY86-5321); The recommended dose for intravitreal aflibercept was 2 mg equivalent to 50 μL. Study treatment was administered at baseline and at monthly intervals until stabilization of disease. When stability was achieved, the treatment interval could be extended based on visual and anatomic outcomes as judged by the treating investigator.

Outcome Measures

Primary Outcome Measures

1. The Proportion of Participants Who Gained ≥ 15 Letters in Best Corrected Visual Acuity (BCVA) on the Early Treatment Diabetic Retinopathy Score (ETDRS) Chart Compared to Baseline [Baseline, Week 24 and Week 76]

   Participants who completed the study with a gain of ≥ 15 letters or dropped the study after Week 24 and having a permanent resolution of macular edema and a gain of ≥ 15 letters from baseline with regard to the latest BCVA assessment. The ETDRS chart includes 70 letters in total, more letters read correctly represents a better visual acuity.

2. The Proportion of Participants With a Mean Treatment Interval Between Injections of ≥ 8 Weeks [From the last actual visit of the initiation phase to Week 76]

   Participants who completed the study with a mean treatment interval between injections of ≥ 8 weeks or dropped out of the study after Week 24 and having a permanent resolution of macular edema

Secondary Outcome Measures

1. The Mean Treatment Interval Between Injections [From baseline to Week 76]

2. The Change in Best Corrected Visual Acuity (BCVA) as Measured by the Early Treatment Diabetic Retinopathy Letter Score (ETDRS) From Baseline [Baseline and Week 24, 52, and 76]

   The ETDRS chart includes 70 letters in total and the letter score ranges from 0 to 100. More letters read correctly results in a higher letter score, which represents better visual acuity

3. The Change in Central Retinal Thickness (CRT) From Baseline [Baseline and Week 24, 52 and 76]

   CRT was measured in the study eye by spectral domain optical coherence tomography (SD-OCT).

4. The Number of Injections Per Participant [From baseline to Week 76]

5. The Proportion of Participants Who Gain ≥ 15 Letters in Best Corrected Visual Acuity (BCVA) on the Early Treatment Diabetic Retinopathy Score (ETDRS) Chart Compared to Baseline [Baseline and Week 24, Week 52]

   The ETDRS chart includes 70 letters in total. More letters read correctly represents a better visual acuity

6. The Proportion of Participants With Change in Retinal Non-perfusion (FA/FP) Status From Baseline [Baseline and Week 24, 52 and 76]

   The change in retinal non-perfusion status by fundus angiography (FA)/fundus photography (FP)-confirmed ischemic disc area. The status was categorized into: no non-perfusion, <10 ischemic disc area, >=10 ischemic disc area and missing status

7. The Proportion of Participants With Absence of Subretinal Fluid [Baseline, week 24, week 52 and week 76]

8. Incidence and Severity of Ocular Treatment-emergent Adverse Events [Up to 30 days after week 76]

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Center-involved macular edema secondary to CRVO for no longer than 3 months (at the screening visit it should be ensured that the subjects will comply with the criterion of ≤ 3 months since onset of macular edema at their scheduled baseline visit).

• Adult subjects diagnosed with macular edema secondary to CRVO who are scheduled to be treated with IVT aflibercept as per investigator's routine treatment practice with the intent to use a T&E regimen after initial dosing.

• Treatment-naïve subjects for macular edema secondary to CRVO.

• Men and women ≥ 18 years of age.

• Documented BCVA of ETDRS letter score of 73 to 24 letters (Snellen equivalent of 20/40 to 20/320) in the study eye.

Exclusion Criteria:

• Previous PRP or macular laser photocoagulation in the study eye.

• Any prior or concomitant ocular treatment (e.g. anti-VEGF therapy, corticosteroids) in the study eye for macular edema secondary to RVO, except dietary supplements or vitamins prior to inclusion in the study. Intraocular anti-VEGF treatment is permitted for the treatment of diseases of fellow eye except for those that are specifically excluded.

• Prior systemic anti-VEGF or corticosteroid therapy, investigational or approved, within the last 3 months before the first dose in the study.

• Previous use of intraocular corticosteroids in the study eye at any time or use of periocular corticosteroids in the study eye within 12 months prior to Day 1.

• Any active intraocular, extraocular, and periocular inflammation or infection in either eye within 4 weeks of screening.

• Any history of allergy to povidone iodine.

• Known serious allergy to the fluorescein sodium for injection in angiography.

• Presence of any contraindications indicated in the EU commission/locally approved label for IVT aflibercept: hypersensitivity to the active substance IVT aflibercept or to any of the excipients; active or suspected ocular or periocular infection; active severe intraocular inflammation.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Albury	New South Wales	Australia	2640
2		Sydney	New South Wales	Australia	2000
3		Parramatta		Australia	2150
4		Calgary	Alberta	Canada	T2H 0C8
5		Hamilton	Ontario	Canada	L8G 5E4
6		London	Ontario	Canada	N6A 4V2
7		Boisbriand	Quebec	Canada	J7H 1S6
8		Sherbrooke	Quebec	Canada	J1G 2V4
9		Quebec		Canada	G1V 1T6
10		Aalborg		Denmark	9100
11		Glostrup		Denmark	2600
12		Bordeaux		France	33076
13		Dijon Cedex		France	BP 1542-21
14		Lyon		France	69004
15		Freiburg	Baden-Württemberg	Germany	79106
16		Heidelberg	Baden-Württemberg	Germany	69120
17		Karlsruhe	Baden-Württemberg	Germany	76133
18		Augsburg	Bayern	Germany	86156
19		Göttingen	Niedersachsen	Germany	37075
20		Düsseldorf	Nordrhein-Westfalen	Germany	40225
21		Hannover	Nordrhein-Westfalen	Germany	30625
22		Köln	Nordrhein-Westfalen	Germany	50935
23		Münster	Nordrhein-Westfalen	Germany	48149
24		Leipzig	Sachsen	Germany	04103
25		Roma	Lazio	Italy	00133
26		Roma	Lazio	Italy	00198
27		Milano	Lombardia	Italy	20132
28		Milano	Lombardia	Italy	20157
29		Ancona	Marche	Italy	60126
30		Pisa	Toscana	Italy	56124
31		Padova	Veneto	Italy	35128
32		Oviedo	Asturias	Spain	33012
33		Sant Cugat del Vallés	Barcelona	Spain	08195
34		Viladecans	Barcelona	Spain	08840
35		Barcelona		Spain	08024
36		Barcelona		Spain	08025
37		Sunderland	Tyne And Wear	United Kingdom	SR2 9HP
38		Bradford	West Yorkshire	United Kingdom	BD9 6RJ
39		Bristol		United Kingdom	BS1 2LX
40		Colchester		United Kingdom	CO3 3NB
41		Liverpool		United Kingdom	L9 7AL
42		Oxford		United Kingdom	OX3 9DU

Sponsors and Collaborators

• Bayer

Investigators

• Study Director: Bayer Study Director, Bayer

Study Documents (Full-Text)

• Study Protocol - Apr 20, 2016
• Statistical Analysis Plan - Nov 14, 2019

More Information

Additional Information:

• Click here to find results for studies related to Bayer products.
• Click here to find information about studies related to Bayer Healthcare products conducted in Europe

Publications

None provided.

• Responsible Party: Bayer
• ClinicalTrials.gov Identifier: NCT02800642
• Other Study ID Numbers: 17514; 2014-003193-17
• First Posted: Jun 15, 2016
• Last Update Posted: Jul 8, 2020
• Last Verified: Jun 1, 2020

• 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.: Yes
• Keywords provided by Bayer: Bayer; Aflibercept; Eylea; Intravitreal
• Additional relevant MeSH terms: Macular Edema; Retinal Vein Occlusion; Aflibercept

Study Results

Participant Flow

Recruitment Details	A total of 244 participants were screened in 42 study centers in 8 countries, the first subject first visit was on 10/Jun/2016 and last subject last visit was on 31/Jun/2019
Pre-assignment Detail	Of the 244 screened participants, 162 subjects completed screening and entered the treatment period

Arm/Group Title	Intravitreal (IVT) Aflibercept
Arm/Group Description	Participants with macular edema secondary to CRVO were treated with 2 mg study drug intravitreal aflibercept over a treatment period of 76 weeks
Period Title: Overall Study
STARTED	162
COMPLETED	137
NOT COMPLETED	25

Baseline Characteristics

Arm/Group Title	Intravitreal (IVT) Aflibercept
Arm/Group Description	Participants with macular edema secondary to CRVO were treated with 2 mg study drug intravitreal aflibercept over a treatment period of 76 weeks
Overall Participants	162
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	66.4 (13.3)
Sex: Female, Male (Count of Participants)
Female	65 40.1%
Male	97 59.9%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	2 1.2%
Not Hispanic or Latino	156 96.3%
Unknown or Not Reported	4 2.5%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	3 1.9%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	1 0.6%
White	154 95.1%
More than one race	0 0%
Unknown or Not Reported	4 2.5%

Outcome Measures

1. Secondary Outcome

Title	The Mean Treatment Interval Between Injections
Time Frame	From baseline to Week 76

Outcome Measure Data

Analysis Population Description

Participants in full analysis set (received any study drug, had a baseline BCVA assessment and at least one post-baseline BCVA assessment) that completed study

Arm/Group Title	Intravitreal (IVT) Aflibercept
Arm/Group Description	Participants with macular edema secondary to CRVO were treated with 2 mg study drug intravitreal aflibercept over a treatment period of 76 weeks
Measure Participants	150
Mean (Standard Deviation) [weeks]	6.37 (1.150)

2. Primary Outcome

Title	The Proportion of Participants Who Gained ≥ 15 Letters in Best Corrected Visual Acuity (BCVA) on the Early Treatment Diabetic Retinopathy Score (ETDRS) Chart Compared to Baseline
Description	Participants who completed the study with a gain of ≥ 15 letters or dropped the study after Week 24 and having a permanent resolution of macular edema and a gain of ≥ 15 letters from baseline with regard to the latest BCVA assessment. The ETDRS chart includes 70 letters in total, more letters read correctly represents a better visual acuity.
Time Frame	Baseline, Week 24 and Week 76

Outcome Measure Data

Analysis Population Description

Full analysis set: included all participants who received any study drug, had a baseline BCVA assessment, and had at least one post-baseline BCVA assessment. Last observation carried forward (LOCF) imputation method.

Arm/Group Title	Intravitreal (IVT) Aflibercept
Arm/Group Description	Participants with macular edema secondary to CRVO were treated with 2 mg study drug intravitreal aflibercept over a treatment period of 76 weeks
Measure Participants	160
Number (95% Confidence Interval) [percent]	65.6 (57.7)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Intravitreal (IVT) Aflibercept
	Comments	The null hypothesis "the proportion of participants with a ≥ 15-letter gain in BCVA at Week 76 is ≤ 40%" on the 2.5% level of significance (one-sided) was performed using the following criterion: If the p value is less than 2.5%, the null hypothesis will be rejected. Otherwise, the null hypothesis will be regarded as not rejected and may still be true
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Exact one-sided 1-sample binomial test
	Comments

3. Primary Outcome

Title	The Proportion of Participants With a Mean Treatment Interval Between Injections of ≥ 8 Weeks
Description	Participants who completed the study with a mean treatment interval between injections of ≥ 8 weeks or dropped out of the study after Week 24 and having a permanent resolution of macular edema
Time Frame	From the last actual visit of the initiation phase to Week 76

Outcome Measure Data

Analysis Population Description

Full analysis set: included all participants who received any study drug, had a baseline BCVA assessment, and had at least one post-baseline BCVA assessment

Arm/Group Title	Intravitreal (IVT) Aflibercept
Arm/Group Description	Participants with macular edema secondary to CRVO were treated with 2 mg study drug intravitreal aflibercept over a treatment period of 76 weeks
Measure Participants	160
Number (95% Confidence Interval) [percent]	45.0 (37.1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Intravitreal (IVT) Aflibercept
	Comments	The null hypothesis "the proportion of participants with a mean treatment interval of ≥ 8 weeks is ≤ 50%" on the 2.5% level of significance (one-sided) was performed using the following criterion: If the p value is less than 2.5%, the null hypothesis will be rejected. Otherwise, the null hypothesis will be regarded as not rejected and may still be true
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	=0.8822
	Comments
	Method	Exact one-sided 1-sample binomial test
	Comments

4. Secondary Outcome

Title	The Change in Best Corrected Visual Acuity (BCVA) as Measured by the Early Treatment Diabetic Retinopathy Letter Score (ETDRS) From Baseline
Description	The ETDRS chart includes 70 letters in total and the letter score ranges from 0 to 100. More letters read correctly results in a higher letter score, which represents better visual acuity
Time Frame	Baseline and Week 24, 52, and 76

Outcome Measure Data

Analysis Population Description

Full analysis set: included all participants who received any study drug, had a baseline BCVA assessment, and had at least one post-baseline BCVA assessment

Arm/Group Title	Intravitreal (IVT) Aflibercept
Arm/Group Description	Participants with macular edema secondary to CRVO were treated with 2 mg study drug intravitreal aflibercept over a treatment period of 76 weeks
Measure Participants	160
Absolute BCVA letter score at baseline	51.9 (16.8)
Absolute BCVA letter score at Week 24	72.4 (16.6)
Absolute BCVA letter score at Week 52	71.8 (18.1)
Absolute BCVA letter score at Week 76	72.3 (18.5)
Change from baseline at Week 24	20.4 (17.0)
Change from baseline at Week 52	19.9 (19.1)
Change from baseline at Week 76	20.3 (19.5)

5. Secondary Outcome

Title	The Change in Central Retinal Thickness (CRT) From Baseline
Description	CRT was measured in the study eye by spectral domain optical coherence tomography (SD-OCT).
Time Frame	Baseline and Week 24, 52 and 76

Outcome Measure Data

Analysis Population Description

Included all participants who received any study drug, had a baseline CRT assessment, and had post-baseline CRT assessment at Week 24, 52 and 76

Arm/Group Title	Intravitreal (IVT) Aflibercept
Arm/Group Description	Participants with macular edema secondary to CRVO were treated with 2 mg study drug intravitreal aflibercept over a treatment period of 76 weeks
Measure Participants	158
Absolute CRT at baseline	759.9 (246.0)
Absolute CRT at Week 24	271.2 (53.1)
Absolute CRT at Week 52	279.8 (106.8)
Absolute CRT at Week 76	265.4 (57.9)
Change from baseline at Week 24	-488.9 (254.6)
Change from baseline at Week 52	-481.3 (266.5)
Change from baseline at Week 76	-496.1 (252.4)

6. Secondary Outcome

Title	The Number of Injections Per Participant
Time Frame	From baseline to Week 76

Outcome Measure Data

Analysis Population Description

Full analysis set: included all participants who received any study drug, had a baseline BCVA assessment, and had at least one post-baseline BCVA assessment

Arm/Group Title	Intravitreal (IVT) Aflibercept
Arm/Group Description	Participants with macular edema secondary to CRVO were treated with 2 mg study drug intravitreal aflibercept over a treatment period of 76 weeks
Measure Participants	160
Mean (Standard Deviation) [injections]	12.2 (2.53)

7. Secondary Outcome

Title	The Proportion of Participants Who Gain ≥ 15 Letters in Best Corrected Visual Acuity (BCVA) on the Early Treatment Diabetic Retinopathy Score (ETDRS) Chart Compared to Baseline
Description	The ETDRS chart includes 70 letters in total. More letters read correctly represents a better visual acuity
Time Frame	Baseline and Week 24, Week 52

Outcome Measure Data

Analysis Population Description

Full analysis set: included all participants who received any study drug, had a baseline BCVA assessment, and had at least one post-baseline BCVA assessment

Arm/Group Title	Intravitreal (IVT) Aflibercept
Arm/Group Description	Participants with macular edema secondary to CRVO were treated with 2 mg study drug intravitreal aflibercept over a treatment period of 76 weeks
Measure Participants	160
Week 24	68.8 (61.0)
Week 52	68.1 (60.3)

8. Secondary Outcome

Title	The Proportion of Participants With Change in Retinal Non-perfusion (FA/FP) Status From Baseline
Description	The change in retinal non-perfusion status by fundus angiography (FA)/fundus photography (FP)-confirmed ischemic disc area. The status was categorized into: no non-perfusion, <10 ischemic disc area, >=10 ischemic disc area and missing status
Time Frame	Baseline and Week 24, 52 and 76

Outcome Measure Data

Analysis Population Description

Full analysis set: included all participants who received any study drug, had a baseline BCVA assessment, and had at least one post-baseline BCVA assessment

Arm/Group Title	Intravitreal (IVT) Aflibercept
Arm/Group Description	Participants with macular edema secondary to CRVO were treated with 2 mg study drug intravitreal aflibercept over a treatment period of 76 weeks
Measure Participants	160
Baseline to week 24: no to <10	4.4
Baseline to week 24: no to >=10	3.8
Baseline to week 24: no to missing	6.3
Baseline to week 24: <10 to no	0.6
Baseline to week 24: <10 to >=10	0.6
Baseline to week 24: <10 to missing	0
Baseline to week 24: >=10 to no	1.3
Baseline to week 24: >=10 to <10	0
Baseline to week 24: >=10 to missing	0.6
Baseline to week 24: missing to no	0
Baseline to week 24: missing to <10	0.6
Baseline to week 24: missing to >=10	0.6
Baseline to week 24: no status change	81.9
Baseline to week 52: no to <10	5.0
Baseline to week 52: no to >=10	5.6
Baseline to week 52: no to missing	10.6
Baseline to week 52: <10 to no	1.9
Baseline to week 52: <10 to >=10	0
Baseline to week 52: <10 to missing	0
Baseline to week 52: >=10 to no	1.9
Baseline to week 52: >=10 to <10	0
Baseline to week 52: >=10 to missing	0
Baseline to week 52: missing to no	0
Baseline to week 52: missing to <10	0.6
Baseline to week 52: missing to >=10	0.6
Baseline to week 52: no status change	73.8
Baseline to week 76: no to <10	3.1
Baseline to week 76: no to >=10	4.4
Baseline to week 76: no to missing	18.1
Baseline to week 76: <10 to no	1.3
Baseline to week 76: <10 to >=10	0.6
Baseline to week 76: <10 to missing	0.6
Baseline to week 76: >=10 to no	0.3
Baseline to week 76: >=10 to <10	0
Baseline to week 76: missing to no	0
Baseline to week 76: missing to <10	0.6
Baseline to week 76: missing to >=10	0.6
Baseline to week 76: no status change	69.4

9. Secondary Outcome

Title	The Proportion of Participants With Absence of Subretinal Fluid
Time Frame	Baseline, week 24, week 52 and week 76

Outcome Measure Data

Analysis Population Description

Full analysis set: included all participants who received any study drug, had a baseline BCVA assessment, and had at least one post-baseline BCVA assessment.

Arm/Group Title	Intravitreal (IVT) Aflibercept
Arm/Group Description	Participants with macular edema secondary to CRVO were treated with 2 mg study drug intravitreal aflibercept over a treatment period of 76 weeks
Measure Participants	160
Baseline	25.6
Week 24	98.7
Week 52	95.4
Week 76	97.8

10. Secondary Outcome

Title	Incidence and Severity of Ocular Treatment-emergent Adverse Events
Time Frame	Up to 30 days after week 76

Outcome Measure Data

Analysis Population Description

Safety analysis set: included all participants who received any study drug

Arm/Group Title	Intravitreal (IVT) Aflibercept
Arm/Group Description	Participants with macular edema secondary to CRVO were treated with 2 mg study drug intravitreal aflibercept over a treatment period of 76 weeks
Measure Participants	162
Any ocular TEAEs	90 55.6%
Severity: mild	39 24.1%
Severity: moderate	43 26.5%
Severity: severe	8 4.9%

Adverse Events

Time Frame	Up to 30 days after week 76
Arm/Group Title	Intravitreal (IVT) Aflibercept
Arm/Group Description	Participants with macular edema secondary to CRVO were treated with 2 mg study drug intravitreal aflibercept over a treatment period of 76 weeks
All Cause Mortality
	Intravitreal (IVT) Aflibercept
	Affected / at Risk (%)	# Events
Total	4/162 (2.5%)
Serious Adverse Events
	Intravitreal (IVT) Aflibercept
	Affected / at Risk (%)	# Events
Total	32/162 (19.8%)
Blood and lymphatic system disorders
Thrombocytopenia	1/162 (0.6%)	1
Cardiac disorders
Atrial fibrillation	4/162 (2.5%)	4
Atrial flutter	1/162 (0.6%)	1
Bundle branch block bilateral	1/162 (0.6%)	1
Cardiac failure acute	1/162 (0.6%)	1
Mitral valve incompetence	1/162 (0.6%)	1
Ventricular tachycardia	1/162 (0.6%)	1
Eye disorders
Amaurosis fugax	1/162 (0.6%)	1
Cataract	1/162 (0.6%)	1
Iridocyclitis	1/162 (0.6%)	1
Retinal artery occlusion	1/162 (0.6%)	1
Retinal degeneration	1/162 (0.6%)	1
Retinal ischaemia	2/162 (1.2%)	2
Retinal vein occlusion	1/162 (0.6%)	1
Visual acuity reduced	1/162 (0.6%)	1
Visual impairment	1/162 (0.6%)	1
Gastrointestinal disorders
Gastric ulcer	2/162 (1.2%)	2
Inguinal hernia	1/162 (0.6%)	1
Hepatobiliary disorders
Cholecystitis acute	1/162 (0.6%)	1
Hepatic haemorrhage	1/162 (0.6%)	1
Infections and infestations
Endocarditis	1/162 (0.6%)	1
Lower respiratory tract infection	1/162 (0.6%)	1
Gastroenteritis viral	1/162 (0.6%)	1
Gastrointestinal viral infection	1/162 (0.6%)	1
Urosepsis	1/162 (0.6%)	2
Pneumonia	1/162 (0.6%)	1
Latent syphilis	1/162 (0.6%)	1
Musculoskeletal and connective tissue disorders
Arthralgia	1/162 (0.6%)	1
Osteoarthritis	1/162 (0.6%)	1
Musculoskeletal pain	1/162 (0.6%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to lymph nodes	1/162 (0.6%)	1
Nervous system disorders
Dementia	1/162 (0.6%)	1
Syncope	1/162 (0.6%)	1
Psychiatric disorders
Delirium	1/162 (0.6%)	1
Renal and urinary disorders
Acute kidney injury	1/162 (0.6%)	1
Renal colic	1/162 (0.6%)	1
Reproductive system and breast disorders
Endometriosis	1/162 (0.6%)	1
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism	1/162 (0.6%)	1
Vascular disorders
Deep vein thrombosis	1/162 (0.6%)	1
Haematoma	1/162 (0.6%)	1
Peripheral arterial occlusive disease	1/162 (0.6%)	1
Other (Not Including Serious) Adverse Events
	Intravitreal (IVT) Aflibercept
	Affected / at Risk (%)	# Events
Total	81/162 (50%)
Eye disorders
Macular oedema	12/162 (7.4%)	13
Conjunctival haemorrhage	18/162 (11.1%)	23
Retinal ischaemia	13/162 (8%)	16
Retinal haemorrhage	14/162 (8.6%)	14
Visual acuity reduced	26/162 (16%)	37
Vitreous detachment	9/162 (5.6%)	11
Foreign body sensation in eyes	9/162 (5.6%)	13
Infections and infestations
Nasopharyngitis	26/162 (16%)	40
Investigations
Intraocular pressure increased	20/162 (12.3%)	40
Vascular disorders
Hypertension	19/162 (11.7%)	25

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.