Surgery, Tissue Plasminogen Activator, Antiangiogenic Agents and Age Related Macular Degeneration Complications (STAR)

Subretinal Haematoma in AMD: Randomized Controlled Study of 2 Therapeutic Approaches in the Antiangiogenic Era

AMD is a disease of the central retina, a zone that enables fine detail activities (reading, detail…). This central zone of the retina can be affected by a haemorrhagic complication when small abnormal vessels suddenly start to bleed inside the retina. Several therapeutic approaches are currently available even though they have never been truly compared. The study will be proposed to patients who need to be treated for haemorrhage of the macula. A certain number of factors will be evaluated to compare the 2 principal approaches currently used in France: surgery followed by injections of an anti-angiogenic OR intravitreal injections of gas followed by injections of anti-angiogenics. This is a multicentre, randomized controlled trial to compare these 2 therapeutic approaches.

These diametrically opposed approaches have very different consequences for patients and in terms of cost for society. The consequences for patients will be immediately measurable so as to determine the best therapeutic approach in terms of functional recovery and the impact of the disease on quality of life, while taking into account the risks inherent to these 2 treatments. The impact on quality of life of these 2 approaches as well as their consequences - an important factor in this disease, which is a cause of sensory handicap - will provide the ophthalmological community with essential information making it possible to validate one or the other of these methods for the management of these haematomas.

Study Overview

• Status: Completed
• Conditions: Subretinal Haematoma Linked to AMD
• Intervention / Treatment: Other: Surgery; Procedure: injections of an antiangiogenic; Other: Intravitreal injections of gas

• Study Type: Interventional
• Enrollment (Actual): 91
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Besancon, France, 25030
    • CHU de Besancon
  • Bordeaux, France, 33000
    • CHU de Bordeaux
  • Colmar, France, 68000
    • CH de Colmar
  • Creteil, France, 94000
    • CHI de Créteil
  • Dijon, France, 21079
    • CHU de Dijon
  • Grenoble, France, 38043
    • Chu de Grenoble
  • Lyon, France, 69004
    • HCL - Hôpital de la Croix-Rousse
  • Metz, France, 57085
    • CHR de Metz-Thionville
  • Mulhouse, France, 68100
    • CH de Mulhouse
  • Nevers, France, 58000
    • CH de Nevers
  • Paris, France, 75019
    • Fondation Ophtalmologique A. de Rothschild
  • Paris, France, 75010
    • Ap-Hp Hopital Lariboisiere
  • Reims, France, 51092
    • CHU de Reims
  • Rouen, France, 76100
    • Clinique Mathilde
  • Strasbourg, France, 67091
    • NHC de STRASBOURG
  • Toulouse, France, 31300
    • CHU de Toulouse - Hôpital Purpan
  • Vandœuvre-lès-Nancy, France, 54500
    • Chu de Nancy

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: N/A
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Patients presenting subretinal haematoma linked to AMD

• Occurring at least14 days before the start of therapy
• With the presence of a component overlying the pigmentary epithelium (PE) on the OCT
• And a diameter greater than two pupillary diameters on the retinal photographs

Patients who have provided oral consent

Patients with National Health Insurance cover

Patients available for monthly follow-up

Patient having an effective contraception for the women old enough to procreate during the treatment and during 6 months which follow his stop.

Exclusion Criteria:

• Subretinal haematoma linked to a cause other than AMD (myopia, angioid streaks…)
• History of subretinal haematoma on the same side
• Cloudy humour making it impossible to photograph the fundus of the eye or carry out angiography
• Component of the haematoma exclusively underlying the pigmentry epithelium
• Haemorrhage without lifting of the retina
• Patients presenting an INR greater than 4, thus contra-indicating surgery
• Patients requiring cataract surgery in the first 3 months of the study
• Patients presenting a contra-indication relative to injection of the antiangiogenic (History of AVC bleeding or unknown origin in the last 6 months or MI in the 3 preceding months)
• Pregnant or breast-feeding woman (the patients do not have to breast-feed during at least 6 months after the administration of the last dose of the antiangiogénique)
• Contraindication in the use of ranibizumab: hypersensitivity in the active ingredient or in one of the excipients, eye infection or périoculaire active or suspected, inflammation intraoculaire active severe, treatments anti-VEGF systematic or eye concomitant,
• Contraindication in the use of bevacizumab: hypersensitivity in the active substance or in one of the excipients, the hypersensitivity in the products of the ovarian cells of Chinese hamster (CHO) or in other antibodies human or humanized recombinants, heavy surgical operation dating less than 28 days, not totally healed surgical wound, history of lung bleeding or hémoptysie
• Contraindication in the use of alteplase: hypersensitivity in the active substance, in the gentamicine (a residue of the present manufacturing process in the state of tracks), or in one of the excipients. As all the thrombolytic agents, contraindication in every case associated to a high hemorrhagic risk (current significant hemorrhagic disorder or during the last six months, hemorrhagic known diathesis, concomitant treatment by oral anticoagulants with effective dose, severe or potentially dangerous, obvious or recent bleeding, histories or suspicion of intra-cranial bleeding, suspicion of sub-arachnoid bleeding or history of sub-arachnoid bleeding bound to an aneurysm, histories of severe lesion of the central nervous system (for example néoplasie, aneurysm, surgical operation intracerebral or intrathecal), recent traumatic external cardiac massage (less than 10 days), delivery, recent draining of a vessel not accessible to the compression (for example draining of the subclavian or jugular vein),severe uncontrolled high blood pressure, bacterial endocarditis, pericarditis, acute pancreatitis, gastrointestinal ulcers documented during the last 3 months, esophageal varices, arterial aneurysm, arterial or venous deformations, neoplasia increasing the hemorrhagic risk, severe hepatic disease, including hepatic insufficiency, cirrhosis, portal hypertension (esophageal varicose veins) and evolutionary hepatitis, surgical operation or important traumas during the last 3 months.
• Contraindication in the use of acetazolamide: hypersensitivity in the acetazolamide or in one of excipients, severe hepatic, renal or suprarenal inadequacies, intolerance in sulphonamide, histories of renal colic, allergy in the wheat (other than the coeliac disease).

Study Plan

How is the study designed?

Design Details

• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: surgery + antiangiogenic; surgery (vitrectomy - air - TPA) with injections of an antiangiogenic	Other: Surgery; Procedure: injections of an antiangiogenic
EXPERIMENTAL: intravitreal injection of gas/TPA + antiangiogenic; intravitreal injection of gas - TPA with injections of an antiangiogenic	Procedure: injections of an antiangiogenic; Other: Intravitreal injections of gas

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Visual acuity measured on the ETDRS scale	Change from inclusion at 3 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Visual acuity measured on the ETDRS scale	At 1 month and 6 months
Area of the scotoma presented by the patient according to the Amsler grid	At 1 month, 3 months and 6 months
Quality of life using the VFQ-25 scale	At 3 months and 6 months
Number of injections of an antiangiogenic at the end of the 6 months of treatment	At 6 months
Number of patients with macular bleeding	At 6 months
Area of hypoautofluorescence using the autofluorescence technique	At 3 and 6 months
Complications rate	At 6 months

Collaborators and Investigators

• Sponsor: Centre Hospitalier Universitaire Dijon

Study record dates

Study Major Dates

• Study Start (ACTUAL): April 28, 2016
• Primary Completion (ACTUAL): May 5, 2020

Study Registration Dates

• First Submitted: September 16, 2015
• First Submitted That Met QC Criteria: September 22, 2015
• First Posted (ESTIMATE): September 23, 2015

Study Record Updates

• Last Update Posted (ACTUAL): February 4, 2021
• Last Update Submitted That Met QC Criteria: February 3, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Hemorrhage; Hematoma; Physiological Effects of Drugs; Antineoplastic Agents; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Angiogenesis Inhibitors
• Other Study ID Numbers: BRON PHRC I 2013