Clinical trial NCT02747030: Phase I RVC With Ocriplasmin for CRVO
Official title: Phase I Study on the Feasibility and Safety of Surgical Stabilizer Assisted Retinal Vein Cannulation With Ocriplasmin Infusion for Central Retinal Vein Occlusion.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Central Retinal Vein Occlusion
Keywords: Central retinal vein occlusion
Retinal endovascular surgery
Retinal vein cannulation
Ocriplasmin
Lead sponsor: Universitaire Ziekenhuizen KU Leuven
Sponsor class: OTHER
Collaborators: name: KU Leuven
First posted: 2016-04-21
Enrollment: 4
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: In central retinal vein occlusion (CRVO) a blood clot blocks the venous outflow of the entire retinal circulation. This leads to retinal and vitreous hemorrhages, retinal edema and neovascularization. The development of a microneedle and surgical stabilizer made it possible to perform a prolonged (10 minutes) retinal vein cannulation with infusion of Ocriplasmin. Ocriplasmin has the advantage over tissue Plasminogen Activator (tPA) that it already is an active enzyme and a strong fibrinolyticum. This study aims to investigate the feasibility and safety of local intravenous Ocriplasmin for CRVO.

Detailed description: Central retinal vein occlusion (CRVO) is the second most common source of permanent blindness in the Western world after diabetic retinopathy. By blocking the outflow pathway for the retinal circulation, visual prognosis is bad on the short and long term. Currently, treatment is mostly focused on treating the secondary effects: macular edema and neovascularization with antiVEGF and/or corticosteroid intravitreal injections and retinal laser photocoagulation. There is however a surgical treatment aimed at displacing the blood clot; a radial optic neurotomy. During this surgical treatment, the vitreous is removed by vitrectomy, after which a radial incision is made in the optic disc. The target of this incision is to open the canal in the lamina cribrosa to improve the blood flow in the central retinal vein. Since the outcome of this procedure is variable and has its inherent risks, mainly because the incision can damage the central retinal artery which is adjacent to the central vein, this procedure is not routinely performed in all vitreoretinal centers.

Following the recent development of a surgical stabilizer and microneedle suitable for retinal vein cannulations, the option for local intravenous administration of fibrinolytic drugs exists. This phase I study aims to investigate the feasibility and safety of surgical stabilizer assisted retinal vein cannulation with local intravenous infusion of Ocriplasmin to dissolve the clot clogging the central retinal vein. Ocriplasmin is the small active part of the larger plasmin molecule. Plasmin itself is formed by enzymatic conversion from plasminogen, a process that is mediated by tissue plasminogen activator (tPA). The amount of plasmin that can be produced is thus highly dependent on the amount of plasminogen that is present nearby the clot. By using Ocriplasmin, this intermediate step can be skipped and the clot will be targeted directly and during the entire time of infusion. By being able to get infusion times up to 10 minutes, abundant clot exposure to Ocriplasmin is guaranteed.

Inclusion will be offered to patients presenting with a recent CRVO, a vitrectomy will be performed augmented with retinal vein cannulation and infusion of ocriplasmin during 10 minutes.

Patients presenting with a recent CRVO (\<2weeks) will be offered inclusion to undergo a vitrectomy with subsequent prolonged retinal vein cannulation and infusion of Ocirplasmin. The surgery is done by placing a microneedle in one of the branch retinal veins at the border of the optic disc. To increase the safety of this procedure a surgical stabilizer was developed. This procedure was abundantly tested and refined in multiple in vivo porcine experiments and the medication (Ocriplasmin) has already been tested for fibrinolytic activity used in 100-fold higher dosis intravenously and intra-arterially.

After the surgery, standard of care follow up with a comprehensive ophthalmological examination and technical investigations is foreseen. The primary outcome measures of this safety and feasiblity study are: technical success to cannulate the retinal vein and inject ocriplasmin to remove the blood clot, number of intervention-related (surgical or pharmacological) complications, duration of infusion.

If necessary; depending on the disease evolution, additional interventions like intravitreal antiVEGF, steroids or laser photocoagulation can be performed.

Eligibility criteria: Inclusion Criteria:

* Patients aged over 18 years
* Recent diagnosis of CRVO
* Onset of symptoms \<10 days
* Visual acuity \< 2/10 in study eye
* Visual acuity \>1/10 in fellow eye
* Central macular thickness \>250µm and \<1000 µm
* Signed informed consent prior to inclusion

Exclusion Criteria:

* Fluorescein allergy
* Active neovascularization (NVD/NVE/NVI/NVA)
* Eye disease other than CRVO or Cataract decreasing vision
* Use of acetazolamide or other drugs potentially affecting macular edema, including systemic steroids \>10mg/d
* History of retinal surgery
* High myopia (\> -10D)
* Contraindication for the use of systemic anticoagulant medication

Primary outcomes:
measure: Feasibility
timeFrame: peroperative
measure: Safety
timeFrame: peroperative until 2 weeks postoperative
Secondary outcomes:
measure: central macular thickness
timeFrame: 2 weeks
measure: surface of non-perfused retina
timeFrame: 2 weeks
measure: visual acuity
timeFrame: 2 weeks
Other outcomes:
Locations:
city: Leuven
country: Belgium
facility: UZ Leuven
state: Vlaams Brabant
Study officials:
affiliation: UZ Leuven
name: Peter Stalmans, MD PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: van Overdam KA, Missotten T, Spielberg LH. Updated cannulation technique for tissue plasminogen activator injection into peripapillary retinal vein for central retinal vein occlusion. Acta Ophthalmol. 2015 Dec;93(8):739-44. doi: 10.1111/aos.12830. Epub 2015 Aug 27.
citation: Verhamme P, Heye S, Peerlinck K, Cahillane G, Tangelder M, Fourneau I, Daenens K, Belmans A, Pakola S, Verhaeghe R, Maleux G. Catheter-directed thrombolysis with microplasmin for acute peripheral arterial occlusion (PAO): an exploratory study. Int Angiol. 2012 Jun;31(3):289-96.
citation: Thijs VN, Peeters A, Vosko M, Aichner F, Schellinger PD, Schneider D, Neumann-Haefelin T, Rother J, Davalos A, Wahlgren N, Verhamme P. Randomized, placebo-controlled, dose-ranging clinical trial of intravenous microplasmin in patients with acute ischemic stroke. Stroke. 2009 Dec;40(12):3789-95. doi: 10.1161/STROKEAHA.109.560201. Epub 2009 Oct 15.
citation: Verhamme P, Jerome M, Goossens G, Devis J, Maleux G, Stas M. A pilot trial of microplasmin in patients with long-term venous access catheter thrombosis. J Thromb Thrombolysis. 2009 Nov;28(4):477-81. doi: 10.1007/s11239-009-0310-x. Epub 2009 Feb 19.