Study of the Benefit of Early Treatment With an Endothelin Inhibitor (Bosentan) in Patients With Sudden Blindness Due to Giant Cell Arteritis: CECIBO (CECIBO)

February 13, 2019 updated by: Centre Hospitalier Universitaire de Nice

Giant cell arteritis , also named Horton's disease, is the most common vasculitis in subjects over 50 years old. The incidence increases with age : from 188 to 290 cases per million inhabitants per year, with a North-South gradient.

The major risk of Horton's disease is blindness, unilateral, occurring in 15 to 20% of cases, sometimes preceded by episodes of transient amaurosis. The decrease in visual acuity is often brutal, irreversible and bilateral in 25 to 50% of cases. The mechanism of this blindness is an arterial ischemia: Acute Anterior Ischemic Optic Neuropathy acute anterior ischaemic optic neuropathy (90%), acute retro-bulbar ischaemic optic neuropathy (5%), occlusion of the central artery of the retina (5%).

The pathogenesis of this brutal ischemia is not fully understood. One of the hypotheses suggests that, during stimulation by an antigen of the environment, preactivated dendritic cells of the arterial wall would stimulate T lymphocytes. These will recruit cells that cause an inflammatory infiltrate polymorphic predominant at the media level. These lesions may be accompanied by destruction of the internal elastic lamina, with inconstant but pathognomonic presence of multinucleated giant cells. All arteries with internal elastic lamina can be affected by parietal inflammation, which results in stenosis and occlusion, explaining the ischemia.

The visual loss is usually abrupt and very severe, leaving the patient with definitely very low or no residual visual acuity.

Conventional treatment currently recommended includes systemic corticosteroid therapy at 1 mg / kg / day, preceded or not by 500 mg pulses of methylprednisolone , and associated with antiplatelet and anticoagulant therapy (LMWH). Despite the decline in visual acuity thus occurred is then always final. Certainly loss of vision has a major impact on the quality of life of patients.

Apart from this lymphocytic inflammation, a process of vascular remodeling is at the origin of the vascular occlusion phenomenon. The endothelin system is a family of amino acids including 3 members: ET1, ET2 and ET3. ET1 is a potent vasoconstrictor. ET1 receptors (ETA and ETB) are expressed in the arteries of patients with giant cell arteritis . The expression of ET1 associated with proliferation of muscle cells in arteries will decrease under the effect of endothelin inhibitors. This has been shown during treatment of pulmonary hypertension. In giant cell arteritis , the endothelin system continues to be very active up to 8 days despite the introduction of systemic corticosteroids. Bosentan is a mixed endothelin receptor antagonist with affinity for both ETA and ETB receptors. This inhibitor is used in treatment of pulmonary artery hypertension, digital ulcerations of systemic sclerosis and critical peripheral arterial ischemia.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Anticipated)

8

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • France
      • Cannes, France
        • CH de Cannes
        • Contact:
          • Lea Blanchouin, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

48 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Decreased visual acuity (BVA) <5 days, regardless of degree of severity, abrupt onset in the context of newly diagnosed or suspected Horton's disease at this loss of visual acuity
  • Able to sign the consent
  • Affiliated to the social security system
  • Already under conventional treatment of Horton's disease or the: requiring: Corticosteroids and + - anti-platelet aggregators and / or LMWH at the discretion of the referring physician for its vasculitis and + - immunosuppressive or biotherapy if necessary.

Exclusion Criteria:

  • Underlying hepatocellular insufficiency known
  • Patient under guardianship or curator
  • Hypersensitivity to the active substance or to any of the excipients
  • Moderate to severe hepatic insufficiency corresponding to class B or C of the Child-Pugh classification
  • Any other ophthalmological pathology explaining the sudden drop in vision: retinal detachment, retinal hemorrhage, posterior uveitis, nonarteritic arterial occlusion, cortical stroke
  • Serum levels of hepatic aminotransferases, aspartate aminotransferases (ASTs) and / or alanine aminotransferases (ALATs), greater than 3 times the upper limit of normal before start of treatment
  • Patient under treatment with cyclosporine A, antiretrovirals, glibenclamide or Rifampicin.
  • Pregnant or lactating women

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Treatment bosentan
Drug: treatment
8 patients will be treat with bosentan at 145 mg per day during 14 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Visual acuity calculated according to the Early Treatment Diabetic Retinopathy Study
Time Frame: 3 months
3 months

Secondary Outcome Measures

Outcome Measure
Time Frame
Visual acuity calculated according to the Early Treatment Diabetic Retinopathy Study
Time Frame: 1 month
1 month
Goldman's one-sided visual field
Time Frame: 3 months
3 months
Numbers of adverse event and serious adverse events
Time Frame: 16 days
16 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Centre Hospitalier Universitaire de Nice

Investigators

  • Principal Investigator: Nathalie Tieulié, MD, Centre Hospitalier Universitaire de Nice

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

March 1, 2019

Primary Completion (Anticipated)

March 1, 2019

Study Completion (Anticipated)

March 1, 2021

Study Registration Dates

First Submitted

February 5, 2019

First Submitted That Met QC Criteria

February 13, 2019

First Posted (Actual)

February 15, 2019

Study Record Updates

Last Update Posted (Actual)

February 15, 2019

Last Update Submitted That Met QC Criteria

February 13, 2019

Last Verified

January 1, 2019

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 18-AOIP-01

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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