IBDV: Pre- and Intra-operative Intravitreal Bevacizumab Injection in Diabetic Vitrectomy

• Sponsor: Seoul National University Bundang Hospital (Other)
• Overall Status: Completed
• CT.gov ID: NCT00745498
• Collaborator: (none)
• Enrollment: 126
• Location: 1
• Arms: 3
• Duration (Months): 28
• Patients Per Site Per Month: 4.5

Study Details

Study Description

Brief Summary

The purpose of this study is to determine the effect of pre- and intra-operative bevacizumab injection on postoperative vitreous hemorrhage after diabetic vitrectomy.

Condition or Disease	Intervention/Treatment	Phase
Proliferative Diabetic Retinopathy; Vitreous Hemorrhage	Drug: Bevacizumab	N/A

Detailed Description

Postoperative vitreous hemorrhage(VH) is a common complication after vitrectomy for proliferative diabetic retinopathy. Persistent or recurrent VH can delay visual rehabilitation and give patients much trouble. There have been efforts to lower the incidence of postoperative VH such as using intraoperative gas tamponade and preoperative bevacizumab injection. Bevacizumab(Avastin) is a potent inhibitor of angiogenesis and has been shown to decrease retinal and iris neovascularization in proliferative diabetic retinopathy. Recently there have been reports showing that preoperative intravitreal bevacizumab (IVB) injection could reduce intraoperative bleeding from abnormal vessels and could make surgery easier and more successful.Our hypothesis is that preoperative bevacizumab injection could reduce postoperative VH by way of decreasing the amount of abnormal vessels and intraoperative injection could also reduce postoperative VH by inhibiting the vessel formation after surgery.

To prove our hypothesis, we started the prospective randomized comparative study to determine the effect of pre- and intra-operative IVB injection on postoperative vitreous hemorrhage after diabetic vitrectomy.

Study Design

• Study Type: Interventional
• Actual Enrollment: 126 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Efficacy Study of Pre- and Intra-operative Intravitreal Bevacizumab Injection on Postoperative Vitreous Hemorrhage After Diabetic Vitrectomy
• Study Start Date: Jun 1, 2008
• Actual Primary Completion Date: Oct 1, 2010
• Actual Study Completion Date: Oct 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Preop IVB Patients will receive intravitreal injection of 1.25 mg of bevacizumab (0.05 ml) 1 to 14 days before vitrectomy	Drug: Bevacizumab; Patients will receive intravitreal injection of 1.25 mg of bevacizumab (0.05 ml); Other Names: avastin
Experimental: Intraop IVB Patients will receive intravitreal injection of 1.25 mg of bevacizumab (0.05 ml) at the end of vitrectomy	Drug: Bevacizumab; Patients will receive intravitreal injection of 1.25 mg of bevacizumab (0.05 ml); Other Names: avastin
No Intervention: No IVB Patients will not receive bevacizumab before nor during vitrectomy

Outcome Measures

Primary Outcome Measures

1. Recurrent VH Incidence (Early and Late) [6 months]

   Recurrent VH was defined as a new episode of grade 1 or more VH occurring more than 1 week after surgery. "Early recurrent VH" was VH occurring <= 4 weeks and "late recurrent VH" was VH occurring >4 weeks after surgery.

Secondary Outcome Measures

1. Initial Time of Vitreous Clearing (ITVC) [6 months]

   The interval in number of days for VH of grade 1 or more observed at postoperative day 1 to clear-up completely. VH of grade 1 was defined as mild vitreous hemorrhage with visible fundus details, but difficult to evaluate the retinal nerve fiber layer or small vessels.

2. Visual Outcome [6 months]

   Best-corrected visual acuity (BCVA) at postoperative 6 months

3. Postoperative Resolution of Neovascularization [6 months]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 20 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patients undergoing first vitrectomy for complications of proliferative diabetic retinopathy such as vitreous hemorrhage, tractional fibrovascular membrane proliferation, tractional or combined retinal detachment)

Exclusion Criteria:

• Follow-up period of less than 6 months

• Intraoperative use of long-acting gas or silicone oil

• Repeat vitrectomy after first vitrectomy for diseases other than vitreous hemorrhage

• Not first vitrectomy

• Uncontrolled hypertension

• Medical history of abnormal blood coagulation

• Time interval between IVB injection and PPV longer than 2 weeks and recent history (within 3 months) of IVB treatment

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Seoul National University Bundang Hospital	Seongnam	Gyunggi-do	Korea, Republic of	463-707

Sponsors and Collaborators

• Seoul National University Bundang Hospital

Investigators

• Principal Investigator: Kyu Hyung Park, M.D., Seoul National Univeristy Bundang Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

• Chen E, Park CH. Use of intravitreal bevacizumab as a preoperative adjunct for tractional retinal detachment repair in severe proliferative diabetic retinopathy. Retina. 2006 Jul-Aug;26(6):699-700.

• Responsible Party: Kyu Hyung Park, Associate Professor, Seoul National University Bundang Hospital
• ClinicalTrials.gov Identifier: NCT00745498
• Other Study ID Numbers: B-0801-053-004
• First Posted: Sep 3, 2008
• Last Update Posted: Dec 21, 2015
• Last Verified: Nov 1, 2015

• Keywords provided by Kyu Hyung Park, Associate Professor, Seoul National University Bundang Hospital: Proliferative diabetic retinopathy; vitrectomy; bevacizumab; vitreous hemorrhage
• Additional relevant MeSH terms: Retinal Diseases; Diabetic Retinopathy; Vitreous Hemorrhage; Hemorrhage; Bevacizumab

Study Results

Participant Flow

Recruitment Details	Consecutive diabetic patients requiring pars plana vitrectomy (PPV) for complications of diabetic retinopathy at Seoul National University Bundang Hospital were referred to assess eligibility.
Pre-assignment Detail	If indications for PPV included proliferative diabetic retinopathy (PDR) related complications such as nonclearing vitreous hemorrhage (VH), macula-involving or -threatening tractional retinal detachment (TRD) or fibrovascular proliferation with vitreoretinal adhesions, the patient was enrolled in the study.

Arm/Group Title	Preop IVB	Introp IVB	No IVB
Arm/Group Description	Patients will receive intravitreal injection of 1.25 mg of bevacizumab (0.05 ml) 1 to 7 days before vitrectomy	Patients will receive intravitreal injection of 1.25 mg of bevacizumab (0.05 ml) at the end of vitrectomy	Patients will not receive bevacizumab before nor during vitrectomy
Period Title: Overall Study
STARTED	41	43	42
COMPLETED	36	37	34
NOT COMPLETED	5	6	8

Baseline Characteristics

Arm/Group Title	Preop IVB	Intraop IVB	No IVB	Total
Arm/Group Description	Patients will receive intravitreal injection of 1.25 mg of bevacizumab (0.05 ml) 1 to 7 days before vitrectomy	Patients will receive intravitreal injection of 1.25 mg of bevacizumab (0.05 ml) at the end of vitrectomy	Patients will not receive bevacizumab before nor during vitrectomy	Total of all reporting groups
Overall Participants	41	43	42	126
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	51.0 (9.5)	55.6 (10.3)	55.0 (11.4)	53.9 (10.5)
Sex: Female, Male (Count of Participants)
Female	15 36.6%	20 46.5%	22 52.4%	57 45.2%
Male	26 63.4%	23 53.5%	20 47.6%	69 54.8%

Outcome Measures

1. Primary Outcome

Title	Recurrent VH Incidence (Early and Late)
Description	Recurrent VH was defined as a new episode of grade 1 or more VH occurring more than 1 week after surgery. "Early recurrent VH" was VH occurring <= 4 weeks and "late recurrent VH" was VH occurring >4 weeks after surgery.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

With study power of 80%, significance level of 0.05, assumption that IVB injection will decrease postoperative VH incidence from 35% to 10%, a sample size of 40 patients for each group was calculated. The ITT approach was used for analysis.

Arm/Group Title	Preop IVB	Intraop IVB	No IVB
Arm/Group Description	Patients will receive intravitreal injection of 1.25 mg of bevacizumab (0.05 ml) 1 to 7 days before vitrectomy	Patients will receive intravitreal injection of 1.25 mg of bevacizumab (0.05 ml) at the end of vitrectomy	Patients will not receive bevacizumab before nor during vitrectomy
Measure Participants	36	37	34
Early	22.2 54.1%	10.8 25.1%	32.4 77.1%
Late	11.1 27.1%	16.2 37.7%	14.7 35%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Preop IVB, Intraop IVB, No IVB
	Comments	With study power of 80%, a significance level of 0.05, and the assumption that IVB injection will decrease postoperative VH incidence from 35% to 10%, a sample size of 40 patients for each group was calculated.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.05
	Comments
	Method	Chi-squared
	Comments

2. Secondary Outcome

Title	Initial Time of Vitreous Clearing (ITVC)
Description	The interval in number of days for VH of grade 1 or more observed at postoperative day 1 to clear-up completely. VH of grade 1 was defined as mild vitreous hemorrhage with visible fundus details, but difficult to evaluate the retinal nerve fiber layer or small vessels.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Preop IVB	Intraop IVB	No IVB
Arm/Group Description	Patients will receive intravitreal injection of 1.25 mg of bevacizumab (0.05 ml) 1 to 7 days before vitrectomy	Patients will receive intravitreal injection of 1.25 mg of bevacizumab (0.05 ml) at the end of vitrectomy	Patients will not receive bevacizumab before nor during vitrectomy
Measure Participants	36	37	34
Mean (Standard Deviation) [days]	26.4 (42.5)	10.3 (8.2)	25.2 (26.1)

3. Secondary Outcome

Title	Visual Outcome
Description	Best-corrected visual acuity (BCVA) at postoperative 6 months
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Preop IVB	Intraop IVB	No IVB
Arm/Group Description	Patients will receive intravitreal injection of 1.25 mg of bevacizumab (0.05 ml) 1 to 7 days before vitrectomy	Patients will receive intravitreal injection of 1.25 mg of bevacizumab (0.05 ml) at the end of vitrectomy	Patients will not receive bevacizumab before nor during vitrectomy
Measure Participants	36	37	34
Mean (Standard Deviation) [logMAR]	0.62 (0.58)	0.68 (0.47)	0.51 (0.56)

4. Secondary Outcome

Title	Postoperative Resolution of Neovascularization
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Arm/Group Title	Preop IVB		Intraop IVB		No IVB
Arm/Group Description	Patients will receive intravitreal injection of 1.25 mg of bevacizumab (0.05 ml) 1 to 7 days before vitrectomy		Patients will receive intravitreal injection of 1.25 mg of bevacizumab (0.05 ml) at the end of vitrectomy		Patients will not receive bevacizumab before nor during vitrectomy
All Cause Mortality
	Preop IVB		Intraop IVB		No IVB
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Preop IVB		Intraop IVB		No IVB
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/41 (0%)		0/43 (0%)		1/42 (2.4%)
Eye disorders
Rhegmatogenous retinal detachment immediately following operation	0/41 (0%)	0	0/43 (0%)	0	1/42 (2.4%)	1
Other (Not Including Serious) Adverse Events
	Preop IVB		Intraop IVB		No IVB
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/41 (2.4%)		3/43 (7%)		1/42 (2.4%)
Eye disorders
neovascular glaucoma following surgery	1/41 (2.4%)	1	3/43 (7%)	3	1/42 (2.4%)	1

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.