Adjuvant Anti-Mineralocorticoid-Receptor Treatment in Anti-VEGF Refractory Neovascular Age-Related Macular Degeneration

NCT ID: NCT03744767

Last Updated: 2018-11-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-09-19
• Study Completion Date: 2015-09-22

Brief Summary

Prospective, non-comparative, mono-center pilot study. Patients with neovascular age-related macular degeneration (nAMD), responding insufficiently to the maximal standard care with monthly intravitreal anti-VEGF injections are given adjuvant oral mineralocorticoid receptor antagonists for 4 months and observed for any changes in vision or retinal structure during the 4 months of adjuvant treatment, plus 2 additional months without adjuvant treatment.

Detailed Description

Hypothesis Systemic anti-Mineralocorticoid-Receptor treatment may be a valuable adjuvant treatment in anti-VEGF refractory nAMD, potentially allowing for better absorption of the exudative fluid.

Aim To estimate the effect of systemic anti-Mineralocorticoid-Receptor treatment on eyes with nAMD which have remained exudative despite monthly anti-VEGF treatment for at least 6 months prior to enrolment.

Objectives Primary objective

• To calculate the changes induced in retinal thickness following adjunct systemic anti-Mineralocorticoid-Receptor treatment Secondary objective
• To calculate the changes induced following adjunct systemic anti-Mineralocorticoid-Receptor treatment in the following ocular parameters

• Thickness of the neuro-retina (foveal)
• Amount of subretinal fluid (foveal and highest elevation)
• Height of retinal pigment epithelium detachment (foveal and highest elevation)
• Central (Subfoveal) choroidal thickness, and at 500um nasal and temporal to the fovea
• Presence / absence of exudative signs on OCT, according to the type of fluid (intraretinal cysts, subretinal fluid)
• Best corrected visual acuity (number of letters)

Medications:

Standard medical treatment (monthly intravitreal injections with anti-VEGF) will be continued during this trial, no current medications will be altered. The medication spironolactone, an MR antagonist will be added to the currently prescribed medications (phase IV). The standard dose of 50mg once daily per os will be prescribed for 3 months (first week 25mg only for treatment introduction and safety), tapered during month 4 (25mg once daily).

In the case of a patient current taking a medication with contra-indications for this drug, then the conflicting medication will be exchanged for an equivalent treatment option, where this is not possible then these patients will be excluded from the study. The patient will be withdrawn from the study in case of any serious side effects attributable to spironolactone (increased K+ above 5.5mmol/l).

Conditions

Neovascular Age-related Macular Degeneration

Study Design

• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Single treatment arm

Group Type: EXPERIMENTAL

Spironolactone 50 MG

Intervention Type: DRUG

oral administration of Spironolactone, 25mg daily for 1 week, then 50mg daily until visit Month 3, followed by 25mg daily from visit Month 3 to visit Month 4

Interventions

Spironolactone 50 MG

oral administration of Spironolactone, 25mg daily for 1 week, then 50mg daily until visit Month 3, followed by 25mg daily from visit Month 3 to visit Month 4

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Diagnosis of neovascular age-related macular degeneration, as confirmed on angiography by a retinal specialist (IM or AA)
• Aged more than 50 years (inherent to AMD)
• Unresponsive to maximal (monthly) anti-VEFG treatment (Ranibizumab or Aflibercept) for at least 6 months: persistant intra- or subretinal fluid on spectral domain optical coherence tomography at each visit 1 month after last injection.
• Treatment with anti-VEGF for nAMD for at least 12 months
• No contra-indications for adjunctive Spironolactone treatment

Exclusion Criteria

• Confounding retinal pathology eg. myopic chorioretinopathy, diabetic retinopathy, vascular occlusion, retinal dystrophy and other retinal pathology
• Polypoidal choroidal vasculopathy
• Vitreomacular traction
• Poor quality OCT (image quality does not allow the grading / measures on OCT)
• High arterial pressure (>160/100)
• K+>5.0 mmol/l at baseline
• Na+ <135 mmol/l at baseline
• Creatinine clearance under 30mL/min (calculation : coefficient*(140-age)*weight/creatinine in the serum; coefficient = 1.23 for males and 1.04 for females)
• Acute renal failure
• Renal dialysis
• Non-specified renal problem
• Arrhythmia
• Cardiovascular comorbidity with thromboembolic risk
• Known hypersensitivity to Spironolactone
• Ongoing medication with eplerenone (Inspra®)
• Decompensated hepatic cirrhosis

• Minimum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Dr Irmela MANTEL

OTHER

Sponsor Role: lead

Responsible Party

Dr Irmela MANTEL

lead consultant, Head of the medical retina service, Principal Investigator, Privatdocent

Responsibility Role: SPONSOR_INVESTIGATOR

Other Identifiers

184/14

Identifier Type: -

Identifier Source: org_study_id