Study of the Benefit of Early Treatment With an Endothelin Inhibitor (Bosentan) in Patients With Sudden Blindness Due to Giant Cell Arteritis: CECIBO (CECIBO)
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| ClinicalTrials.gov Identifier: NCT03841734 |
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Recruitment Status : Unknown
Verified January 2019 by Centre Hospitalier Universitaire de Nice.
Recruitment status was: Not yet recruiting
First Posted : February 15, 2019
Last Update Posted : February 15, 2019
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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 |
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 8 participants |
| Allocation: | N/A |
| 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 |
| Arm | Intervention/treatment |
|---|---|
| Experimental: Treatment bosentan |
Drug: treatment
8 patients will be treat with bosentan at 145 mg per day during 14 days |
- Visual acuity calculated according to the Early Treatment Diabetic Retinopathy Study [ Time Frame: 3 months ]
- Visual acuity calculated according to the Early Treatment Diabetic Retinopathy Study [ Time Frame: 1 month ]
- Goldman's one-sided visual field [ Time Frame: 3 months ]
- Numbers of adverse event and serious adverse events [ Time Frame: 16 days ]
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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
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 ClinicalTrials.gov identifier (NCT number): NCT03841734
| Contact: Nathalie Tieulié, MD | 04 92 03 90 19 | tieulie.n@chu-nice.fr |
| France | |
| CH de Cannes | |
| Cannes, France | |
| Contact: Lea Blanchouin, MD | |
| Principal Investigator: | Nathalie Tieulié, MD | Centre Hospitalier Universitaire de Nice |
Other Publications:
| Responsible Party: | Centre Hospitalier Universitaire de Nice |
| ClinicalTrials.gov Identifier: | NCT03841734 |
| 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 |
| Studies a U.S. FDA-regulated Drug Product: | No |
| Studies a U.S. FDA-regulated Device Product: | No |
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Polymyalgia Rheumatica Giant Cell Arteritis Blindness Vision, Low Arteritis Vasculitis 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 |