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TENecteplase in Central Retinal Artery Occlusion Stuy (TenCRAOS) (TenCRAOS)

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ClinicalTrials.gov Identifier: NCT04526951
Recruitment Status : Recruiting
First Posted : August 26, 2020
Last Update Posted : March 3, 2021
Sponsor:
Information provided by (Responsible Party):
Anne Hege Aamodt, Oslo University Hospital

Brief Summary:

TENecteplase in Central Retinal Artery Occlusion (TenCRAOS): A Prospective, randomized-controlled, double-dummy, double-blind phase 3 multi-centre trial of TNK 0.25 mg/kg + placebo vs. ASA + placebo (2 arms with 1:1 block randomization).

A Prospective, randomized-controlled, double-dummy, double-blind phase 3 multi-centre trial of TNK 0.25 mg/kg + placebo vs. ASA + placebo (2 arms with 1:1 block randomization). At all participating centers, ophthalmologists are involved in the diagnosis and visual outcome measurements using a standardized protocol. The patients will be promptly examined by the ophthalmologist. As soon as the CRAO is diagnosed by the ophthalmologist, the patients will be managed in the stroke unit during treatment, monitoring, and medical investigations. After treatment in the stroke unit, the patients will be re-examined by an ophthalmologist and a neurologist as an out-patient at (30 ±5) and 90 (±15) days


Condition or disease Intervention/treatment Phase
Central Retinal Artery Occlusion Drug: Intravenous injection of Tenecteplase and one dose of placebo tablet Drug: One tablet of Acetylsalicylic Acid and one dose of IV placebo Phase 3

Detailed Description:
Central retinal artery occlusion (CRAO) is an ophthalmologic emergency that, without prompt revascularization, bears high risk of permanent blindness. The condition is typically the result of an artery-to-artery embolism from a carotid plaque or cardio embolism. A recent meta-analysis of observational data indicates that prompt revascularization with systemic thrombolysis might improve outcome. A randomized controlled trial of early systemic thrombolysis for CRAO is therefore warranted. The aim of this project is to assess the effect of systemic tissue plasminogen activator tenecteplase versus placebo administered within 4.5 hours of CRAO onset in patients admitted to the participating hospitals in Europe. The main endpoint is the proportion of patients with ≤ 0.7 logMAR visual acuity 30 (±5) days after treatment, representing an improvement in visual acuity of at least 0.3 logMAR, equal to at least 15 letters/three lines on a visual acuity chart. In addition, we will access differences in visual field parameters and patient reported outcome measures between the groups. This study is based on a broad collaboration and interaction between leading ophthalmologists and neurologists in European centres.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 78 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: A prospective, randomized-controlled, double-dummy, double-blind phase 3 multi-centre trial of TNK 0.25 mg/kg + placebo vs. ASA + placebo (2 arms with 1:1 block randomisation). At all participating centers, ophthalmologists are involved in the diagnosis and visual outcome measurements using a standardized protocol. The patients will be promptly examined by the ophthalmologist. As soon as the CRAO is diagnosed by the ophthalmologist, the patients will be managed in the stroke unit during treatment, monitoring, and medical investigations. After treatment in the stroke unit, the patients will be re-examined by an ophthalmologist and a neurologist as an out-patient at (30 ±5) and 90 (±15) days.
Masking: Single (Participant)
Primary Purpose: Treatment
Official Title: TENecteplase in Central Retinal Artery Occlusion Study (TenCRAOS): A Randomized Placebo-controlled Trial of Early Systemic Tenecteplase Treatment in Patients With Central Retinal Artery Occlusion.
Actual Study Start Date : October 30, 2020
Estimated Primary Completion Date : October 31, 2023
Estimated Study Completion Date : January 31, 2024

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: Tenecteplase
The total dose of tenecteplase is 0.25 mg/kg body weight, maximum 25 mg. The total dose will be given as an intravenous bolus
Drug: Intravenous injection of Tenecteplase and one dose of placebo tablet
Drug: Tenecteplase Tenecteplase administered as an intravenous injection (0.25 mg/kg body weigh; maximum 25 mg)
Other Name: Metalyse

Active Comparator: acetylsalicylic acid
one tablet of aspirin 300 mg Other Name: Aspirin
Drug: One tablet of Acetylsalicylic Acid and one dose of IV placebo
300 mg Acetylsalisylic acid
Other Name: Aspirin




Primary Outcome Measures :
  1. Proportion of patients with ≤ 0.7 logMAR visual acuity in the affected eye at 30 (±5) days after treatment, representing an improvement in visual acuity of at least 0.3 logMAR (intention-to-treat (ITT) analysis). [ Time Frame: 30 (±5) days ]

Secondary Outcome Measures :
  1. Proportion of patients with ≤ 0.5 logMAR visual acuity in the affected eye at 30 (±5) and 90 (±15) days. [ Time Frame: 30 (±5) and 90 (±15) days ]
  2. Mean improvement in logMAR visual acuity in the affected eye from baseline to 30 (±5) and 90 (±15) days. [ Time Frame: 30 (±5) and 90 (±15) days ]
  3. Proportion of patients with visual recovery (logMAR ≤ 0.7) and (logMAR ≤ 0.5) in the affected eye 30 (±5) and 90 (±15) days in patients who were treated with tenecteplase within 3 hours of onset [ Time Frame: 30 (±5) and 90 (±15) days ]
  4. Number of test points seen (of 100) on monocular Esterman perimetry at 30 (±5) and 90 (±15) days [ Time Frame: 30 (±5) and 90 (±15) days ]
  5. Acute ischemic lesions on follow-up on diffusion-weighted (DWI) MRI or on brain CT at baseline and 24hrs. [ Time Frame: 24 hours ]
  6. National Institutes of Health Stroke Scale score (NIHSS) at 24hrs and discharge. [ Time Frame: 24 hours ]
  7. Modified Rankin Scale score (mRS) at discharge, 30 (±5) and 90 days (±15) days. [ Time Frame: Discharge, 30 (±5) and 90 days (±15) days. ]
  8. Mean score on National Eye Institute Visual Function Questionnaire (NEI-VFQ 25) at 30 (±5) and 90 (±15) days [ Time Frame: 30 (±5) and 90 (±15) days ]
    Visual function related quality of life at 30 and 90 days. Measures the dimensions of self-reported vision-targeted health status that are most important for persons who have chronic eye diseases. 100 = best possible, 0 = worst possible

  9. Mean score on EQ-5D at 30 (±5) and 90 (±15) days [ Time Frame: 30 (±5) and 90 (±15) days ]
    Quality of life reported at 30 and 90 days. Health status is measured in terms of five dimensions (5D); mobility, self-care, usual activities, pain/discomfort, and anxiety/depression.

  10. Presence of ocular neovascularisation at 30 (±5) and 90 (±15) days [ Time Frame: 30 (±5) and 90 (±15) days ]

Other Outcome Measures:
  1. All-cause and stroke-related death at discharge, 30 (±5) and 90 (±15) days. [ Time Frame: Discharge assessed up to 7 days , 30 (±5) and 90 (±15) days ]
  2. Proportion of patients with any intracranial haemorrhage at 24 hrs [ Time Frame: 24 hours ]
  3. Proportion of patients with symptomatic intracranial haemorrhage until discharge. [ Time Frame: at discharge, assessed up to 7 days ]
  4. Proportion of patients with complications such as systemic bleeding at 24 hrs, discharge and 30 (±5) days [ Time Frame: 24 hours, at discharge assessed up to 7 days and 30 (±5) days ]
  5. Other serious adverse events [ Time Frame: 24 hours, at discharge, 30 (±5) days and 90 days (±15) days. ]
  6. Occurrence of adverse events [ Time Frame: 24 hours, at discharge assessed up to 7 days, 30 (±5) days and 90 days (±15) days. ]
  7. Retrobulbar spot sign detection using Duplex/Doppler ultrasound at baseline, point-of-care ultrasound (POCUS) [ Time Frame: 30 (±5) and 90 (±15) days ]
  8. Retrobulbar spot sign and central retinal artery recanalisation using Duplex/Doppler ultrasound at 24h and discharge [ Time Frame: 24 hours and at discharge assessed up to 7 days ]
  9. Macular optical coherence tomography (OCT) volume scans and macular OCT angiography (OCT-A) at 30 and 90 days [ Time Frame: 30 (±5) and 90 (±15) days ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Non-arteritic central retinal artery occlusion with ≥ 1.0 logMAR visual acuitiy and symptoms lasting less than 4.5 hours.
  2. Ability to administer the Investigator Medicinal Product (IMP) within 4.5 hours of symptom onset.
  3. Age ≥18 years.
  4. Informed written consent of the patient.
  5. A woman of childbearing potential (WOCBP) must confirm that in her opinion, she cannot be pregnant, OR if there is a possibility that she is pregnant, a negative pregnancy test must be confirmed before any IMP is given.

Exclusion Criteria:

  1. No other active intervention targeting CRAO.
  2. Branch retinal artery occlusion, cilioretinal artery supplying the macula, combined arterial-venous occlusion, proliferative diabetic retinopathy, elevated intraocular pressure (> 30 mmHg) or clinical suspicion of ophthalmic artery occlusion occlusion (e.g. choroidal nonperfusion, absence of cherry red spot, no light perception).
  3. Systemic diseases; severe general diseases, systemic arterial hypertension (blood pressure >185/110 mmHg), despite medical therapy, or clinical suspicion of acute systemic inflammation.
  4. Presence of intracranial haemorrhage on brain MRI/CT.
  5. Medical history: heart attack within the last 6 weeks, intracerebral bleeding or neurosurgical operation within the last 4 weeks, therapy with anticoagulation, allergic reaction to contrast agent, hemorrhagic diathesis, aneurysms, inflammatory vascular diseases (eg, giant cell arteritis, granulomatosis with polyangitis), endocarditis, or gastric ulcer.
  6. No willingness and ability of the patient to participate in all follow-up examinations.
  7. Pregnancy (if suspicion of pregnancy s-hCG or u-hCG must be negative).
  8. Allergy or intolerance to any ingredients of IMP or placebo or gentamicin.
  9. Other conditions / circumstances likely to lead to poor treatment adherence (eg, history of poor compliance, alcohol or drug dependency, no fixed abode).
  10. Significant bleeding disorder either at present or within the past 6 months.
  11. Effective oral anticoagulant treatment, eg, warfarin sodium (INR >1.3).
  12. Effective anticoagulant treatment with heparin or low molecular weight heparin the last 48 hours.
  13. Any history of central nervous system damage (ie, neoplasm, aneurysm, intracranial or spinal surgery).
  14. Known hemorrhagic diathesis.
  15. Major surgery, biopsy of a parenchymal organ, or significant trauma within the past 2 months (this includes any trauma associated with acute myocardial infarction).
  16. Recent non-compressible vessel puncture within 2 weeks.
  17. Recent trauma to the head or cranium.
  18. Prolonged cardiopulmonary resuscitation (>2 minutes) within the past 2 weeks.
  19. Acute pericarditis and/or subacute bacterial endocarditis.
  20. Acute pancreatitis.
  21. Severe hepatic dysfunction, including hepatic failure, cirrhosis, portal hypertension (oesophageal varices) and active hepatitis.
  22. Active peptic ulceration.
  23. Arterial aneurysm and known arterial/venous malformation.
  24. Neoplasm with increased bleeding risk.
  25. Any known history of hemorrhagic stroke or stroke of unknown origin.
  26. Known history of ischemic stroke or transient ischemic attack in the preceding 3 months.
  27. Dementia.

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 ClinicalTrials.gov identifier (NCT number): NCT04526951


Contacts
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Contact: Anne Hege Aamodt +47 23074976 a.h.aamodt@medisin.uio.no

Locations
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Sponsors and Collaborators
Oslo University Hospital
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Responsible Party: Anne Hege Aamodt, Senior Consultant, MD, PhD, Oslo University Hospital
ClinicalTrials.gov Identifier: NCT04526951    
Other Study ID Numbers: Oslo UH
2018-002546-36 ( EudraCT Number )
2019/327 ( Other Identifier: Ethics Committee in Norway )
First Posted: August 26, 2020    Key Record Dates
Last Update Posted: March 3, 2021
Last Verified: March 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Supporting Materials: Study Protocol
Informed Consent Form (ICF)

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Anne Hege Aamodt, Oslo University Hospital:
thrombolysis tenecteplase
Additional relevant MeSH terms:
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Retinal Artery Occlusion
Arterial Occlusive Diseases
Vascular Diseases
Cardiovascular Diseases
Retinal Diseases
Eye Diseases
Aspirin
Tenecteplase
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Antirheumatic Agents
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Platelet Aggregation Inhibitors
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Antipyretics