Paroxysmal Nocturnal HemoglobinuriaNCT03329365
Paroxysmal Nocturnal Hemoglobinuria in ESUS & ETUS
An observational study of Paroxysmal Nocturnal Hemoglobinuria and Embolic Stroke of Undetermined Source, run by London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's at 1 site in Canada.
Trial summary
Paroxysmal nocturnal hemoglobinuria (PNH) is a rare acquired clonal hematological disorder, which can cause arterial or venous thrombosis. The frequency of PNH in young patients (< 50 years old) with embolic stroke (ESUS), transient ischemic attack (ETUS) or superior sagittal sinus cerebral venous thrombosis… Read more about this study
- Who is it for?
- Ages 18 to 50 years
- Conditions the study is for
- Paroxysmal Nocturnal Hemoglobinuria, Embolic Stroke of Undetermined Source, Transient Ischemic Attack
- How many people
- 200 participants
- Where
- 1 siteCanada
- Study dates
- 1 Nov 2018to 29 Mar 2027
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 50 years
- All sexes
- No healthy volunteers
- Adult
Study population: Patients with ESUS, ETUS, or SSS-CVTUS attending the Urgent TIA and Stroke Prevention Clinic or admitted to University or Victoria Hospital, in London, Ontario, Canada.
Who may be able to join
- General:
- Participants with embolic ischemic stroke (ESUS), embolic transient ischemic attack (ETUS) or cerebral venous thrombosis (CVTUS) of undetermined source.
- For transient ischemic attack (TIA):
- One of the following criteria needs to be fulfilled to be considered as embolic TIA:
- Focal symptoms suggesting involvement of de cerebral cortex in the middle cerebral artery (MCA) territory (e.g., aphasia, neglect, apraxia, dystextia, anosognosia, isolated leg, arm or hand weakness). Some of these symptoms have been described as associated with subcortical fibers connecting cortical areas as well but, despite this, they are usually related to cortical localizations. Patients with hemianopia will be included only if hemianopia is not the primary symptom or an isolated symptom.
- Rapidly resolving hemispheric symptoms. This concept comprises two components: (a) sudden onset hemispheric syndrome: sudden onset of symptoms and signs implicating extensive ischemia in the internal carotid artery (ICA) or MCA territories, including hemiparesis, hemianopia, conjugate eye deviation, other cortical signs, or altered consciousness; and (b) spectacular shrinking deficit: improvement within 24 hours (approximately).
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- Symptoms involving more than one vascular territory within a single hemisphere (e.g. left sided weakness + left homonymous hemianopia) or both (e.g., left sided weakness and aphasia in a right-handed patient).
- Simultaneous embolization to other organs (e.g., bowel, spleen, liver, kidneys, toes).
- Transient monocular blindness (amaurosis fugax) with no evidence of giant cell arteritis (e.g., normal erythrocyte sedimentation rate).
- No definite cortical symptoms but neuroimaging evidence of prior (chronic) typical infarct (wedge shaped, involving the cerebral cortex).
- All of the following criteria must be fulfilled to be considered as TIA of undetermined source:
- No neuroimaging evidence of an acute brain infarct within the brain region(s) responsible for the presenting symptoms.
- Absence of extracranial or intracranial atherosclerosis causing ≥50% luminal stenosis in arteries supplying the area of ischemia.
- No major-risk cardioembolic source of embolism.
- No other specific cause of stroke identified (e.g., arteritis, dissection, migraine, vasospasm, or drug abuse).
- No persistent neurological focal symptoms at the time of neurological examination. The presence of persistent neurological focal symptoms in the absence of a visible brain infarct on DWI MRI will be regarded as a "clinically confirmed stroke with negative DWI MRI".
Who cannot join
- General:
- Inability to provide informed consent
- For stroke patients:
- Evidence of >50% stenosis of the internal carotid artery (ICA) or MCA ipsilateral to the qualifying ischemic stroke on neurovascular imaging studies.
- Ischemic stroke involving deep structures and measuring < 15 mm on diffusion-weighted (DWI) magnetic resonance imaging (MRI). Cortical strokes measuring <15 mm will qualify to be included in the study.
- Evidence of a cause explaining the stroke (e.g. hypercoagulable state or any other major source of cardiac embolism).
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- For TIA patients:
- Patients no fulfilling the criteria for ETUS.
- For cerebral venous thrombosis patients:
- Subjects without involvement of the superior sagittal sinus (SSS)
- Subjects with an evident cause explaining the thrombosis (e.g., thrombophilia)
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Paroxysmal Nocturnal Hemoglobinuria and Embolic Strokes of Undetermined Source (ESUS) and Transient Ischemic Attacks of Undetermined Source (ETUS)
Paroxysmal nocturnal hemoglobinuria (PNH) is a rare acquired clonal hematological disorder, which can cause arterial or venous thrombosis. The frequency of PNH in young patients (< 50 years old) with embolic stroke (ESUS), transient ischemic attack (ETUS) or superior sagittal sinus cerebral venous thrombosis (SSS-CVTUS) of undetermined source, is currently unknown. This study proposes to recruit ESUS, ETUS, SSS-CVTUS patients to determine the frequency of PNH diagnosis confirmed by flow cytometry in these patient populations.
Read the detailed description
Paroxysmal nocturnal hemoglobinuria (PNH) is a rare acquired clonal hematological disorder leading to red blood cells hemolysis and thrombosis. PNH has been reported to be the cause of cerebral venous thrombosis and embolic ischemic strokes and is sometimes diagnosed after the ischemic event. In young patients with embolic ischemic stroke of undetermined source (ESUS), thrombophilia is usually investigated. However, access to PNH testing is limited. PNH is rarely investigated in stroke patients and its contribution to the pathophysiology of ESUS is unknown. The investigators hypothesize that this condition is underdiagnosed, resulting in potential preventive opportunities being lost, since PNH can be successfully treated.
This observational study aims to determine the frequency of PNH among young (≤50 years old) patients with recent ESUS or embolic transient ischemic attacks (TIA) of undetermined source (ETUS) and patients with SSS-CVT of undetermined source (SSS-CVTUS).
Patients with ESUS or ETUS will be first screened for: (a) evidence of hemolysis based on their plasma lactate dehydrogenase (LDH) levels, (b) unexplained anemia based on their hemoglobin (Hb) levels, and (c) unexplained cytopenia (e.g., neutropenia and thrombocytopenia). Flow cytometry analysis for PNH will be performed with blood samples collected from subjects with abnormal level of plasma LDH (1.5X ULN) or unexplained anemia or cytopenia.
Patients with SSS-CVTUS will undergo flow cytometry without prior screening.
In addition, plasma and DNA samples will be collected in an optional sub-study for future analysis of DNA mutations related to specific PNH phenotypes in patients with stroke.
- Conditions
- Paroxysmal Nocturnal Hemoglobinuria, Embolic Stroke of Undetermined Source, Transient Ischemic Attack, Cerebral Vein Thrombosis
- Keywords
- Flow cytometry, Lactate dehydrogenase (LDH) release, Anemia, Cytopenia
- Medical subject headings
- Hemoglobinuria, Paroxysmal, Ischemic Attack, Transient, Intracranial Thrombosis, Anemia, Cytopenia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| ESUS/ETUS | Patients with embolic ischemic stroke or transient ischemic attack of undetermined source | |
| SSS-CVTUS | Patients with superior sagittal sinus cerebral venous thrombosis of undetermined source |
What is being measured
The primary outcome is the main question the study is designed to answer.
Frequency of PNH in ESUS/ETUS/SSS-CVTUS
Percentage of patients with flow-cytometry-confirmed PNH
Measured: At recruitment
Secondary outcomes (2)
Frequency of PNH in ESUS/ETUS
Percentage of ESUS/ETUS patients with flow-cytometry-confirmed PNH
Measured: At recruitment
Frequency of PNH in SSS-CVT
Percentage of SSS-CVTUS patients with flow-cytometry-confirmed PNH
Measured: At recruitment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Nov 2017
- Study start1 Nov 2018
- Primary completion29 Mar 2023
- Study completion29 Mar 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Paroxysmal Nocturnal HemoglobinuriaStudies of the same condition, open and under way.
- More trials run by London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph'sThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 200 participants (estimated)
Sponsor and investigators
- Lead sponsor
- London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's
- Sponsor type
- University, hospital or other
- Collaborators
- Alexion Pharmaceuticals, Inc.
- Responsible party
- Sponsor
- Investigators
- Luciano A Sposato, MD, Principal investigator, London Health Sciences Center, Western University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03329365
- Sponsor's protocol ID
- HSREB109061
- Status last verified
- Oct 2025
- First submitted
- 30 Oct 2017
- Last updated
- 18 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 18 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Paroxysmal Nocturnal Hemoglobinuria and Embolic Strokes of Undetermined Source (ESUS) and Transient Ischemic Attacks of Undetermined Source (ETUS)
- ClinicalTrials.gov ID
- NCT03329365
- Acronym / sponsor ID
- HSREB109061
- Conditions
- Paroxysmal Nocturnal Hemoglobinuria, Embolic Stroke of Undetermined Source, Transient Ischemic Attack, Cerebral Vein Thrombosis
- Keywords
- Flow cytometry, Lactate dehydrogenase (LDH) release, Anemia, Cytopenia
- Study type
- Observational
- Recruitment status
- Active, not recruiting
- Enrolment
- 200 participants (estimated)
- Lead sponsor
- London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph'sUniversity, hospital or other
- Collaborators
- Alexion Pharmaceuticals, Inc.
- Study start
- 1 Nov 2018 (actual)
- Primary completion
- 29 Mar 2023 (actual)
- Study completion
- 29 Mar 2027 (estimated)
- First posted
- 6 Nov 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Paroxysmal nocturnal hemoglobinuria (PNH) is a rare acquired clonal hematological disorder, which can cause arterial or venous thrombosis. The frequency of PNH in young patients (< 50 years old) with embolic stroke (ESUS), transient ischemic attack (ETUS) or superior sagittal sinus cerebral venous thrombosis (SSS-CVTUS) of undetermined source, is currently unknown. This study proposes to recruit ESUS, ETUS, SSS-CVTUS patients to determine the frequency of PNH diagnosis confirmed by flow cytometry in these patient populations.
Detailed description
Paroxysmal nocturnal hemoglobinuria (PNH) is a rare acquired clonal hematological disorder leading to red blood cells hemolysis and thrombosis. PNH has been reported to be the cause of cerebral venous thrombosis and embolic ischemic strokes and is sometimes diagnosed after the ischemic event. In young patients with embolic ischemic stroke of undetermined source (ESUS), thrombophilia is usually investigated. However, access to PNH testing is limited. PNH is rarely investigated in stroke patients and its contribution to the pathophysiology of ESUS is unknown. The investigators hypothesize that this condition is underdiagnosed, resulting in potential preventive opportunities being lost, since PNH can be successfully treated.
This observational study aims to determine the frequency of PNH among young (≤50 years old) patients with recent ESUS or embolic transient ischemic attacks (TIA) of undetermined source (ETUS) and patients with SSS-CVT of undetermined source (SSS-CVTUS).
Patients with ESUS or ETUS will be first screened for: (a) evidence of hemolysis based on their plasma lactate dehydrogenase (LDH) levels, (b) unexplained anemia based on their hemoglobin (Hb) levels, and (c) unexplained cytopenia (e.g., neutropenia and thrombocytopenia). Flow cytometry analysis for PNH will be performed with blood samples collected from subjects with abnormal level of plasma LDH (1.5X ULN) or unexplained anemia or cytopenia.
Patients with SSS-CVTUS will undergo flow cytometry without prior screening.
In addition, plasma and DNA samples will be collected in an optional sub-study for future analysis of DNA mutations related to specific PNH phenotypes in patients with stroke.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| ESUS/ETUS | – | –Patients with embolic ischemic stroke or transient ischemic attack of undetermined source |
| SSS-CVTUS | – | –Patients with superior sagittal sinus cerebral venous thrombosis of undetermined source |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
- Study population
- Patients with ESUS, ETUS, or SSS-CVTUS attending the Urgent TIA and Stroke Prevention Clinic or admitted to University or Victoria Hospital, in London, Ontario, Canada.
Key inclusion criteria (16 listed)
- Participants with embolic ischemic stroke (ESUS), embolic transient ischemic attack (ETUS) or cerebral venous thrombosis (CVTUS) of undetermined source.
- Focal symptoms suggesting involvement of de cerebral cortex in the middle cerebral artery (MCA) territory (e.g., aphasia, neglect, apraxia, dystextia, anosognosia, isolated leg, arm or hand weakness). Some of these symptoms have been described as associated with subcortical fibers connecting cortical areas as well but, despite this, they are usually related to cortical localizations. Patients with hemianopia will be included only if hemianopia is not the primary symptom or an isolated symptom.
- Rapidly resolving hemispheric symptoms. This concept comprises two components: (a) sudden onset hemispheric syndrome: sudden onset of symptoms and signs implicating extensive ischemia in the internal carotid artery (ICA) or MCA territories, including hemiparesis, hemianopia, conjugate eye deviation, other cortical signs, or altered consciousness; and (b) spectacular shrinking deficit: improvement within 24 hours (approximately).
- Symptoms involving more than one vascular territory within a single hemisphere (e.g. left sided weakness + left homonymous hemianopia) or both (e.g., left sided weakness and aphasia in a right-handed patient).
- Simultaneous embolization to other organs (e.g., bowel, spleen, liver, kidneys, toes).
Key exclusion criteria (11 listed)
- Inability to provide informed consent
- Evidence of >50% stenosis of the internal carotid artery (ICA) or MCA ipsilateral to the qualifying ischemic stroke on neurovascular imaging studies.
- Ischemic stroke involving deep structures and measuring < 15 mm on diffusion-weighted (DWI) magnetic resonance imaging (MRI). Cortical strokes measuring <15 mm will qualify to be included in the study.
- Evidence of a cause explaining the stroke (e.g. hypercoagulable state or any other major source of cardiac embolism).
- Patients no fulfilling the criteria for ETUS.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Frequency of PNH in ESUS/ETUS/SSS-CVTUS
Time frame: At recruitment
Percentage of patients with flow-cytometry-confirmed PNH
2 secondary outcomes
Frequency of PNH in ESUS/ETUS
Time frame: At recruitment
Frequency of PNH in SSS-CVT
Time frame: At recruitment
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Sep 2026.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Luciano A Sposato, MD principal investigator
London Health Sciences Center, Western University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Paroxysmal Nocturnal Hemoglobinuria and Embolic Stroke of Undetermined Source, run by London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 16 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 18 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Frequency of PNH in ESUS/ETUS/SSS-CVTUS (time frame: At recruitment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Sep 2026; AzTrials last refreshed its copy on 6 Nov 2026.