So no measurement of 100% recovery. Guess it's not important to stroke researchers. Talk to survivors sometime, you'll get an earful. If they haven't been bamboozled by their stroke medical 'professionals' using the tyranny of low expectations to lower their goals for recovery.
The third Intensive Care Bundle with Blood Pressure Reduction in Acute Cerebral Haemorrhage Trial (INTERACT3): an international, stepped wedge cluster randomised controlled trial
- et al.
Summary
Background
Early
control of elevated blood pressure is the most promising treatment for
acute intracerebral haemorrhage. We aimed to establish whether
implementing a goal-directed care bundle incorporating protocols for
early intensive blood pressure lowering and management algorithms for
hyperglycaemia, pyrexia, and abnormal anticoagulation, implemented in a
hospital setting, could improve outcomes for patients with acute
spontaneous intracerebral haemorrhage.
Methods
We
performed a pragmatic, international, multicentre, blinded endpoint,
stepped wedge cluster randomised controlled trial at hospitals in nine
low-income and middle-income countries (Brazil, China, India, Mexico,
Nigeria, Pakistan, Peru, Sri Lanka, and Viet Nam) and one high-income
country (Chile). Hospitals were eligible if they had no or inconsistent
relevant, disease-specific protocols, and were willing to implement the
care bundle to consecutive patients (aged ≥18 years) with
imaging-confirmed spontaneous intracerebral haemorrhage presenting
within 6 h of the onset of symptoms, had a local champion, and could
provide the required study data. Hospitals were centrally randomly
allocated using permuted blocks to three sequences of implementation,
stratified by country and the projected number of patients to be
recruited over the 12 months of the study period. These sequences had
four periods that dictated the order in which the hospitals were to
switch from the control usual care procedure to the intervention
implementation of the care bundle procedure to different clusters of
patients in a stepped manner. To avoid contamination, details of the
intervention, sequence, and allocation periods were concealed from sites
until they had completed the usual care control periods. The care
bundle protocol included the early intensive lowering of systolic blood
pressure (target <140 mm Hg), strict glucose control (target 6·1–7·8
mmol/L in those without diabetes and 7·8–10·0 mmol/L in those with
diabetes), antipyrexia treatment (target body temperature ≤37·5°C), and
rapid reversal of warfarin-related anticoagulation (target international
normalised ratio <1·5) within 1 h of treatment, in patients where
these variables were abnormal. Analyses were performed according to a
modified intention-to-treat population with available outcome data (ie,
excluding sites that withdrew during the study). The primary outcome was
functional recovery, measured with the modified Rankin scale (mRS;
range 0 [no symptoms] to 6 [death]) at 6 months by masked research
staff, analysed using proportional ordinal logistic regression to assess
the distribution in scores on the mRS, with adjustments for cluster
(hospital site), group assignment of cluster per period, and time
(6-month periods from Dec 12, 2017). This trial is registered at Clinicaltrials.gov (NCT03209258) and the Chinese Clinical Trial Registry (ChiCTR-IOC-17011787) and is completed.
Findings
Between
May 27, 2017, and July 8, 2021, 206 hospitals were assessed for
eligibility, of which 144 hospitals in ten countries agreed to join and
were randomly assigned in the trial, but 22 hospitals withdrew before
starting to enrol patients and another hospital was withdrawn and their
data on enrolled patients was deleted because regulatory approval was
not obtained. Between Dec 12, 2017, and Dec 31, 2021, 10 857 patients
were screened but 3821 were excluded. Overall, the modified
intention-to-treat population included 7036 patients enrolled at 121
hospitals, with 3221 assigned to the care bundle group and 3815 to the
usual care group, with primary outcome data available in 2892 patients
in the care bundle group and 3363 patients in the usual care group. The
likelihood of a poor functional outcome was lower in the care bundle
group (common odds ratio 0·86; 95% CI 0·76–0·97; p=0·015). The
favourable shift in mRS scores in the care bundle group was generally
consistent across a range of sensitivity analyses that included
additional adjustments for country and patient variables (0·84;
0·73–0·97; p=0·017), and with different approaches to the use of
multiple imputations for missing data. Patients in the care bundle group
had fewer serious adverse events than those in the usual care group
(16·0% vs 20·1%; p=0·0098).
Interpretation
Implementation
of a care bundle protocol for intensive blood pressure lowering and
other management algorithms for physiological control within several
hours of the onset of symptoms resulted in improved functional outcome (Use factual words instead of these weasel words.)
for patients with acute intracerebral haemorrhage. Hospitals should
incorporate this approach into clinical practice as part of active
management for this serious condition.
Funding
Joint
Global Health Trials scheme from the Department of Health and Social
Care, the Foreign, Commonwealth & Development Office, and the
Medical Research Council and Wellcome Trust; West China Hospital; the
National Health and Medical Research Council of Australia; Sichuan
Credit Pharmaceutic and Takeda China.
Introduction
Intracerebral
haemorrhage is the most serious and least treatable form of stroke and
accounts for approximately 20% of the almost 20 million new strokes that
occur globally each year.1
Most cases of intracerebral haemorrhage occur in low-income and
middle-income countries (LMICs), where there is a high prevalence of
hypertension, unhealthy diets (eg, a high salt intake), and other risk
factors.2
Because elevated blood pressure is common after the onset of
intracerebral haemorrhage and is strongly associated with a poor
outcome, a central component of the management of patients is to provide
treatment to lower blood pressure towards a systolic target of 140 mm
Hg or less.3,4,5,6,7 However, inconsistent results across randomised controlled trials8,9 and little evidence specifically in patients with a large intracerebral haemorrhage or who require neurosurgical intervention10
has restricted the uptake of this strategy in clinical practice where
guidelines generally provide an intermediate strength to their
recommendation.3, 4, 5, 6, 7
Moreover, the absence of a proven medical or surgical treatment for
intracerebral haemorrhage has resulted in an absence of urgency to treat
these patients and a low threshold for the withdrawal of active care in
these patients,11, 12 which contrasts sharply with modern systems of care for patients with acute ischaemic stroke.
Efforts
to improve the success of randomised controlled trials in identifying
an effective treatment for intracerebral haemorrhage have included the
use of clinical and imaging variables to define a potential responder
group with a high likelihood of early neurological deterioration from
ongoing haemorrhage or haematoma growth.13, 14, 15
Another effort has been to extend the assessment of functional outcome
beyond the conventional 90 days, because recovery from intracerebral
haemorrhage takes longer than from acute ischaemic stroke.16
Assessing combinations of interventions as part of a multifaceted care
bundle might also offer advantages, as shown in an Australian cluster
clinical trial where the implementation of a treatment protocol for
hyperglycaemia, fever, and dysphagia improved outcome from acute stroke.17
Further support for this approach was provided by a single-site,
so-called before-and-after study in the UK, where the implementation of a
quality improvement protocol that included the reversal of
anticoagulation, intensive blood pressure lowering, and rapid triage to
neurosurgery and critical care was associated with a lower 30-day case
fatality after intracerebral haemorrhage.18
A post-hoc analysis of the second phase of the international Intensive
Blood Pressure Reduction in Acute Cerebral Haemorrhage Trial (INTERACT2)19
showed that higher scores assigned for any elevation in the baseline of
systolic blood pressure, glucose, body temperature, and previous use of
anticoagulants in participants independently predicted a poor
functional outcome after intracerebral haemorrhage. These issues
informed the design of the third Intensive Care Bundle with Blood
Pressure Reduction in Acute Cerebral Haemorrhage Trial (INTERACT3), with
the aim of establishing whether a goal-directed care bundle protocol,
comprising early intensive lowering of blood pressure with other
management protocols for abnormal physiological variables, improves
functional outcome in a broad range of patients with acute spontaneous
intracerebral haemorrhage.
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