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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03841734
Recruitment Status : Not yet recruiting
First Posted : February 15, 2019
Last Update Posted : February 15, 2019
Information provided by (Responsible Party):
Centre Hospitalier Universitaire de Nice

Brief Summary:

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.

Condition or disease Intervention/treatment Phase
Arteritis, Giant Cell Blindness and Low Vision Drug: treatment Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 8 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Study of the Benefit of Early Treatment With an Endothelin Inhibitor (Bosentan) in Patients With Sudden Blindness Due to Giant Cell Arteritis: CECIBO
Estimated Study Start Date : March 2019
Estimated Primary Completion Date : March 2019
Estimated Study Completion Date : March 2021

Resource links provided by the National Library of Medicine

Drug Information available for: Bosentan

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

Primary Outcome Measures :
  1. Visual acuity calculated according to the Early Treatment Diabetic Retinopathy Study [ Time Frame: 3 months ]

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

Information from the National Library of Medicine

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Ages Eligible for Study:   50 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03841734

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Contact: Nathalie Tieulié, MD 04 92 03 90 19

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CH de Cannes Not yet recruiting
Cannes, France
Contact: Lea Blanchouin, MD         
Sponsors and Collaborators
Centre Hospitalier Universitaire de Nice
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Principal Investigator: Nathalie Tieulié, MD Centre Hospitalier Universitaire de Nice

Publications of Results:
Other Publications:

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Responsible Party: Centre Hospitalier Universitaire de Nice Identifier: NCT03841734     History of Changes
Other Study ID Numbers: 18-AOIP-01
First Posted: February 15, 2019    Key Record Dates
Last Update Posted: February 15, 2019
Last Verified: January 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Polymyalgia Rheumatica
Giant Cell Arteritis
Vision, Low
Vascular Diseases
Cardiovascular Diseases
Vasculitis, Central Nervous System
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Skin Diseases, Vascular
Skin Diseases
Autoimmune Diseases
Immune System Diseases
Muscular Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Vision Disorders
Sensation Disorders
Neurologic Manifestations
Eye Diseases
Signs and Symptoms
Antihypertensive Agents
Endothelin Receptor Antagonists