Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT03737344 |
| Other study ID # |
R118439 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
Phase 2
|
| First received |
|
| Last updated |
|
| Start date |
May 17, 2019 |
| Est. completion date |
April 30, 2021 |
Study information
| Verified date |
October 2021 |
| Source |
University of Manchester |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
This trial will help inform the development of a new treatment for intracerebral haemorrhage
(ICH; also known as haemorrhagic stroke). ICH is a type of stroke caused by spontaneous
bleeding into the brain. In the hours to days after bleeding occurs, inflammation develops in
the brain around the haematoma (collection of blood in the brain). Inflammation is the body's
natural response to injury, however when it continues unchecked there is a risk that the
brain tissue around the haematoma will become swollen. This type of swelling can worsen
existing stroke symptoms or cause new deficits such as speech disturbance and limb weakness,
which can lead to long term disability.
The level of inflammation in the blood is high after ICH. The investigators want to
investigate whether blocking this inflammation can improve overall recovery. The
investigators research group has extensively investigated the use of a well-established
anti-inflammatory drug, Kineret® in trials with patients who have suffered a stroke or brain
haemorrhage. Kineret® is similar to a naturally-produced protein called interleukin-1
receptor antagonist (IL-1Ra) and is already licensed to treat patients with rheumatoid
arthritis. The investigators have evidence from these previous studies that Kineret® reduced
levels of inflammation in the blood after ischaemic stroke (caused by a blockage in an
artery). However, in order to develop Kineret® as a treatment for ICH, the investigators need
to know if it reduces levels of inflammation present in the blood following ICH and if it
reduces swelling in the brain.
Description:
The investigators know from previous studies that the level of inflammation in the blood is
high after haemorrhagic stroke and want to investigate whether blocking this inflammation can
improve outcomes. The only current treatments for haemorrhagic stroke are aimed at
significantly reducing the blood pressure and reversing the action of any anticoagulants
(e.g. warfarin) where necessary. Surgery to remove the blood clot is not an option for all
participants and the benefits of this are not clear.
The investigators research group has extensively investigated the use of a well-established
anti-inflammatory drug, Kineret® in trials with participants who have suffered a stroke or
brain haemorrhage. Kineret® is similar to a naturally-produced protein called interleukin-1
receptor antagonist (IL-1Ra) and is already licensed to treat patients with rheumatoid
arthritis. The investigators have evidence from these previous studies that Kineret® reduced
levels of inflammation in the blood after ischaemic stroke (caused by a blockage in an
artery). In another trial, the investigators collected samples of the haematoma blot clot
removed during surgery in 47 participants who had suffered a haemorrhagic stroke. These
participants were taking part in a trial of 'keyhole' surgery as a treatment for haemorrhagic
stroke. The investigators found that higher levels of naturally occurring IL-1Ra in and
around the haematoma blood clot is linked to less brain swelling a few days later. This
suggests that Kineret® may reduce swelling in the brain after haemorrhagic stroke. However,
in order to develop Kineret® as a treatment for haemorrhagic stroke, the investigators need
to know if it reduces levels of inflammation present in the blood and if it reduces swelling
in the brain.
The investigators also want to investigate whether blocking inflammation can improve outcomes
following ICH. If the results of this trial show promise, it could support the decision to
run a much larger trial to establish whether lowering inflammation improves recovery after
haemorrhagic stroke.
Patients admitted to a neurosurgical centre within 8 hours of intracerebral haemorrhage (ICH)
on brain imaging will be considered for study participation. Potential participants will be
identified by the clinical team and will be referred to the research teams at the sites
following usual and established pathways. These pathways may include potential participants
being identified by; (i) Screening the acute referral databases/medical records, (ii)
Attendance at ward round and, (iii) Referral by Accident and Emergency team. All members of
the research teams at the sites have an existing working relationship with the clinical teams
and are employed by the research site (hospital Trust). This procedure is employed at sites
in order to identify potential participants for all acute and hyper acute research studies.
Capacity to consent may be an issue within this patient group. An appropriately trained
member of the research team will carry out a formal assessment of capacity, where
appropriate. Where it is not possible to obtain consent from the patient due to lack of
capacity, the investigators will seek consent from their personal legal representative. If
the patient lacks capacity to consent to participation and no personal legal representative
exists, the decision to include the patient will be made by a senior member of the clinical
team who is independent of the research team (professional legal representative).
In the event that a patient has the capacity to consent to participation, but is unable to
complete and sign the relevant consent form due to physical difficulties resulting from their
clinical condition or pre-existing physical impairments (e.g. visual difficulties or limb
weaknesses), witnessed, verbal consent will be obtained. The patient will be asked to orally
confirm their willingness to participate in each stage of the trial to the professional legal
representative (most likely a member of the clinical team independent of the research group)
who will then be asked to confirm this consent in writing. In the event that the physical
difficulties resolve during the patient's inclusion in the trial, a further consent form will
be completed.
Where initial consent is obtained from the patient's personal legal representative or the
professional legal representative, the capacity of the patient to consent will be reassessed
before each research assessment/intervention. If the patient regains capacity, they will be
given information about the trial and asked to confirm willingness to continue trial
participation by signing a consent form. Where initial consent is given by the patient, it
will be made clear that they will remain in the trial should capacity be lost unless the
decision to withdraw them is made by their representative, the research team, or by their
clinical team.
Consent to trial participation will include sharing of personal contact data with the trial
centre in order to conduct follow up assessment and the optional consent to storage of blood
samples for use in other ethically-approved research.
Following consent, the research nurse will conduct an initial 'baseline' assessment. This
will be written in the medical notes and also in an individual research file (Case Report
Form). This first assessment will record details of how well the patient was at the time of
inclusion in the trial as well as how well they were in the 3 months before stroke. The
assessment will also record information such as age, sex and ethnicity and past medical
history (including recent infections, previous stroke, risk factors, medications and
vaccinations). A physical examination will record measurements of temperature, heart rate and
blood pressure. A similar assessment will be repeated on each of the following 4 days after
symptom-onset. The final assessment will be completed the morning after the final injection
has been given. After this assessment the research team will ask the patient to verbally
reconfirm consent that contact details can be passed to the coordinating centre (Chief
Investigator's Team at University of Manchester) In addition to the baseline assessment, a
research blood sample will be obtained to measure levels of inflammation at baseline. This
blood sample will be up to 10ml (2 teaspoons) and will be taken from existing venous lines
(where possible) to minimise discomfort for the participant.
After obtaining the baseline blood samples and baseline assessments, the participant will be
randomised to treatment arm or placebo. The system will generate a unique participant
identification number which will be used on all documentation from this point to identify
subsequent samples, for communications and for data collection purposes. First dose of trial
medication must be delivered within 8 hours of ICH and as soon as possible after
randomisation.
Participants will receive 6 injections of identical doses of Trial Drug (Kineret® or placebo)
over 3 days after ICH. However, only half the participants will receive Kineret® and the
other half will receive placebo (dummy drug). The investigators will measure and compare
levels of inflammation in the blood of both groups of participants before and after treatment
with Trial Drug to assess if inflammation is lower in those who receive Kineret® compared to
those given placebo. The investigators will also assess all brain imaging performed on trial
participants in both treatment groups during their in-patient stay to see if there are
differences in the number showing signs of further bleeding and brain swelling. If the
results of this trial show promise, it could support the decision to run a much larger trial
to establish whether lowering inflammation improves recovery after ICH.
At approximately 3 days after randomisation, the patient will undergo a repeat CT brain scan
as part of the research trial. This scan is the same type as the one performed at admission.
Although this scan is being performed as part of the research trial, the results will also be
available to the doctors looking after the patient and may assist them in deciding on
specific treatments. This scan will take approximately 10 minutes to perform but the
participant may be away from the ward or department for up to 45 minutes. The scan will be
used by the researchers who will compare it to brain imaging performed on admission to
hospital.
In addition to the CT scan, participants may also be asked to undergo a Magnetic Resonance
(MR) brain scan between 2-4 days from the onset of the stroke symptoms. This is optional and
is dependent on availability of hospital scan appointments. Members of the research team at
the recruiting hospital will record everything that happens to the patient during their
in-patient stay. At 30 days after randomisation, participants will be followed up to further
check their well-being. If the patient is still in hospital on this date, this assessment may
be performed face-to-face by a member of the research team. However, if the participant has
been discharged home or returned to their local hospital, the researcher will perform this
assessment by telephone with the participant or their relative/friend if they are not able or
their local healthcare provider. It is expected that this assessment will take around 45
minutes.
The participant will be contacted again by telephone at approximately 90 days (3 months) by a
member of the research team at the trial coordinating centre in Manchester. This assessment
will assess the participant's recovery after ICH and will include questions about their mood,
level of fatigue and quality of life. It is expected that this assessment will take around 45
minutes. If for any reason, the participant is unable to complete this assessment, a member
of their family may answer the questions on their behalf.
This will complete the patient's participation in the trial. With the participant's
permission, the researchers at the recruiting hospital will contact the participant's family
doctor (GP), Consultant and any other Health Care Professional involved in their care to let
them know of the patient's participation in the trial.
