Surgical Stabilizer Assisted RVC With rtPA for CRVO

Phase Ib Study on Surgical Stabilizer Assisted Retinal Vein Cannulation (RVC) With tPA Infusion Confirmed by Intraoperative Angio-optical Coherence Tomography (Angio-OCT) for the Treatment of Central Retinal Vein Occlusion (CRVO).

This phase Ib study investigates the safety and efficacy of performing a retinal vein cannulation with recombinant tissue Plasminogen Activator infusion into a retinal vein with the help of an updated dedicated surgical stabiliser for the treatment of central retinal vein occlusion.

Study Overview

• Status: Withdrawn
• Conditions: Central Retinal Vein Occlusion
• Intervention / Treatment: Procedure: Vitrectomy with retinal vein cannulation and intravenous rtPA (Actilyse) infusion up to 1mg.; Drug: Intravenous Infusion

Detailed Description

Investigator-initiated, unmasked, single-arm, mono-center, prospective, interventional case series phase Ib trial. In line with the previous phase I trial, this trial will be biphasic; first 3 patients will be included, when the procedure and product prove to be safe and an added value is noted from the intra-operative OCT-angiography, another 3 will be included afterwards (≥21 days between last inclusion of the first group and first inclusion of the second group).

• Study Type: Interventional
• Phase: Phase 1

Contacts and Locations

Study Locations

• Belgium
  • Leuven, Belgium, 3000
    • Universitaire Ziekenhuizen Leuven

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients aged over 18 years
• Recent diagnosis (<8 weeks) of CRVO
• Recent onset of symptoms (<12 weeks)
• Visual acuity < 5/10 in study eye
• Visual acuity >1/10 in fellow eye
• Central macular thickness >250µm
• Signed informed consent prior to inclusion

Exclusion Criteria:

• Fluorescein allergy
• Active neovascularization
• Eye disease other than CRVO or Cataract decreasing central vision
• History of retinal surgery
• High myopia (> -10D)
• Contraindication for the use of systemic anticoagulant medication
• Extensive macular ischemia noted on fluo-angiography

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: RVC with tPA for CRVO; Single arm phase I open label study were CRVO patients will have a vitrectomy with retinal vein cannulation and a single infusion of tPA (0.25mg/ml) intravenously with a maximum dose of 1mg.

Procedure: Vitrectomy with retinal vein cannulation and intravenous rtPA (Actilyse) infusion up to 1mg.; Standard 3-port pars plana vitrectomy with surgical stabilizer assisted ( surgical robot) retinal vein cannulation with recombinant tissue Plasminogen Activator (Actilyse-0.25mg/ml) infusion with a maximal dose of 1mg..; Drug: Intravenous Infusion; Intravenous infusion in a retinal vein with rtPA (Actilyse 0.25mg/ml).; Other Names: Recombinant tissue Plasminogen Activator (rtPA)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Success rate of retinal vein cannulation	successful cannulation defined as peroperatively seen washout of blood in the cannulated retinal vein. The success rate is defined as the number of successful cannulations divided by the total number of cannulation attempts.	10 min
number of intervention-related surgical complications	These exist of the intra-operative occurence of: retinal vein tear (visually seen by the surgeon); uncontrollable vitreous cavity hemorrhage (as seen by the surgeon); retinal tear in the proximity of the cannulation site (as seen by the surgeon); intra-/subretinal injection (as seen by the surgeon); breakage of the needle (as seen by the surgeon); failure of stabilizer in holding the instrument immobilized in a certain position (as seen by the surgeon)	7 days
duration of infusion	The time of infusion measured during surgery with a maximum of 10 minutes	10 minutes
number of intervention-related non-surgical complications	The postoperative occurence of: hemorrhagic cerebrovascular accidents due to rtPA (confirmed by CT-scan and neurological examination after referral to the neurologist); large hemorrhage elsewhere to be related with the use of rtPA (as confirmed by clinical examination and/or CT-scan/ultrasound after referral to vascular surgeon)	7 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
change in visual acuity after 6 to 8 weeks	best corrected visual acuity tested with ETDRS chart	6-8 weeks
change in central macular thickness after 6 to 8 weeks	measurement of central macular thickness with spectral domain-OCT	6-8 weeks
intra-/postoperative complications not related to the surgical stabilizer / retinal vein cannulation / rtPA	- complications of intraocular surgery: wound leak tested with concentrated fluorescein (Seidel effect present/absent); endophthalmitis as seen with the slit lamp/ultrasonography; post-operative macular edema objectivated with OCT imaging; vitreous hemorrhage > 2 weeks after intervention as seen at the slit lamp and confirmed with ultrasonography; development of neovascularization as seen at the slit lamp / fluorescein angiogram	7 days
intra-/postoperative complications not related to the surgical stabilizer / retinal vein cannulation / rtPA	- complications during cataract surgery: iris hemorrhage as seen through the surgical microscope (present/absent); choroidal swelling as seen through the surgical microscope (present/absent); suprachoroidal hemorrhage as seen through the surgical microscope (present/absent); capsule tear as seen through the surgical microscope (present/absent); dropped lens/intraocular lens (IOL). Recombinant tissue Plasminogen Activator (rtPA) as seen through the surgical microscope (occurred/not occurred)	7 days
intra-/postoperative complications not related to the surgical stabilizer / retinal vein cannulation / rtPA	- complications during vitrectomy: retinal tears as seen through the surgical microscope (occurred/not occurred); vitreous hemorrhage as seen through the surgical microscope (occurred/not occurred); choroidal swelling as seen through the surgical microscope (present/absent); suprachoroidal hemorrhage as seen through the surgical microscope (present/absent)	7 days
change in retinal flow intraoperatively visualized with OCT-angiography	OCT-angiography visualized flow inside the retinal veins with the intraoperative OCT device; if there is flow the blood vessel is imaged in bright white, if there is no flow the blood vessel is not visible with angio-OCT.	1 hour

Collaborators and Investigators

• Sponsor: Universitaire Ziekenhuizen KU Leuven
• Investigators: Principal Investigator: Peter Stalmans, UZ Leuven

Study record dates

Study Major Dates

• Study Start (Anticipated): October 16, 2018
• Primary Completion (Actual): December 10, 2021
• Study Completion (Actual): December 10, 2021

Study Registration Dates

• First Submitted: November 20, 2017
• First Submitted That Met QC Criteria: January 24, 2018
• First Posted (Actual): January 31, 2018

Study Record Updates

• Last Update Posted (Actual): March 23, 2023
• Last Update Submitted That Met QC Criteria: March 22, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Eye Diseases; Retinal Diseases; Embolism and Thrombosis; Venous Thrombosis; Thrombosis; Retinal Vein Occlusion; Molecular Mechanisms of Pharmacological Action; Fibrinolytic Agents; Fibrin Modulating Agents; Tissue Plasminogen Activator; Plasminogen
• Other Study ID Numbers: S61283

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No