A statistical analysis protocol for the time-differentiated target temperature management after out-of-hospital cardiac arrest (TTH48) clinical trial (original) (raw)
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Trials, 2016
The application of therapeutic hypothermia (TH) for 12 to 24 hours following out-of-hospital cardiac arrest (OHCA) has been associated with decreased mortality and improved neurological function. However, the optimal duration of cooling is not known. We aimed to investigate whether targeted temperature management (TTM) at 33 ± 1 °C for 48 hours compared to 24 hours results in a better long-term neurological outcome. The TTH48 trial is an investigator-initiated pragmatic international trial in which patients resuscitated from OHCA are randomised to TTM at 33 ± 1 °C for either 24 or 48 hours. Inclusion criteria are: age older than 17 and below 80 years; presumed cardiac origin of arrest; and Glasgow Coma Score (GCS) <8, on admission. The primary outcome is neurological outcome at 6 months using the Cerebral Performance Category score (CPC) by an assessor blinded to treatment allocation and dichotomised to good (CPC 1-2) or poor (CPC 3-5) outcome. Secondary outcomes are: 6-month mor...
Targeted temperature management after out-of-hospital cardiac arrest: certainties and uncertainties
Targeted temperature management was adopted as part of the treatment of unconscious survivors of out-ofhospital cardiac arrest following the publication of two landmark studies which concluded that mild induced hypothermia (32°C to 34°C) improved survival and neurological outcome, substantiating the neuroprotective effect of mild hypothermia described in experimental animal data . Subsequently, this therapy was recommended by international guidelines and became a standard of care. Although both trials [1,2] had exclusion criteria limiting generalizability, mild induced hypothermia was applied to the wider cardiac arrest population.
Targeted temperature management and neuroprognostication after cardiac arrest: A survey in Belgium
Resuscitation, 2015
The prognosis of patients who are admitted to the hospital after cardiac arrest often relies on neurological examination, which could be significantly influenced by the use of sedative drugs or the implementation of targeted temperature management. The need for early and accurate prognostication is crucial as up to 15-20% of patients could be considered as having a poor outcome and may undergo withdrawal of life-sustaining therapies while a complete neurological recovery is still possible. As current practice in Belgium is still based on a very early assessment of neurological function in these patients, the Belgian Society of Intensive Care Medicine created a multidisciplinary Task Force to provide an optimal approach for monitoring and refine prognosis of CA survivors. This Task Force underlined the importance to use a multimodal approach using several additional tools (e.g., electrophysiological tests, neuroimaging, biomarkers) and to refer cases with uncertain prognosis to specialized centers to better evaluate the extent of brain injury in these patients.
JAMA neurology, 2015
Brain injury affects neurologic function and quality of life in survivors after cardiac arrest. To compare the effects of 2 target temperature regimens on long-term cognitive function and quality of life after cardiac arrest. In this multicenter, international, parallel group, assessor-masked randomized clinical trial performed from November 11, 2010, through January 10, 2013, we enrolled 950 unconscious adults with cardiac arrest of presumed cardiac cause from 36 intensive care units in Europe and Australia. Eleven patients were excluded from analysis for a total sample size of 939. Targeted temperature management at 33°C vs 36°C. Cognitive function was measured by the Mini-Mental State Examination (MMSE) and assessed by observers through the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE). Patients reported their activities in daily life and mental recovery through Two Simple Questions and their quality of life through the Medical Outcomes Study 36-Item Short ...
Circulation Reports
for the J-PULSE-Hypo-DC Trial Study Group Background: The 2020 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care recommend that comatose patients with return of spontaneous circulation after cardiac arrest have targeted temperature management (TTM). However, the duration of TTM remains to be elucidated. Methods and Results: We conducted a cluster randomized trial in 10 hospitals to compare 12-24 vs. 36 h of cooling in patients with cardiac arrest who received TTM. The primary outcome was the incidence, within 1 month, of complications including bleeding requiring transfusion, infection, arrhythmias, decreasing blood pressure, shivering, convulsions, and major adverse cardiovascular events. Secondary outcomes were mortality and favorable neurological outcome (Cerebral Performance Categories 1-2) at 3 months. Random-effects models with clustered effects were used to calculate risk ratios (RR). Data of 185 patients were analyzed (12-to 24-h group, n=100 in 5 hospitals; 36-h group, n=85 in 5 hospitals). The incidence of complications within 1 month did not differ between the 2 groups (40% vs. 34%; RR 1.04, 95% confidence interval [CI] 0.67-1.61, P=0.860). Favorable neurological outcomes at 3 months were comparable between the 2 groups (64% vs. 62%; RR 0.91, 95% CI 0.72-1.14, P=0.387). Conclusions: TTM at 34°C for 12-24 h did not significantly reduce the incidence of complications. This study did not show superiority of TTM at 34°C for 12-24 h for neurologic outcomes.
Journal of the American Heart Association, 2017
Out-of-hospital cardiac arrest (OHCA) results in significant morbidity and mortality, primarily from neurologic injury. Predicting neurologic outcome early post-OHCA remains difficult in patients receiving targeted temperature management. Retrospective analysis was performed on consecutive OHCA patients receiving targeted temperature management (32-34°C) for 24 hours at a tertiary-care center from 2008 to 2012 (development cohort, n=122). The primary outcome was favorable neurologic outcome at hospital discharge, defined as cerebral performance category 1 to 2 (poor 3-5). Patient demographics, pre-OHCA diagnoses, and initial laboratory studies post-resuscitation were compared between favorable and poor neurologic outcomes with multivariable logistic regression used to develop a simple scoring system (C-GRApH). The C-GRApH score ranges 0 to 5 using equally weighted variables: (C): coronary artery disease, known pre-OHCA; (G): glucose ≥200 mg/dL; (R): rhythm of arrest not ventricular ...
JAMA network open, 2020
IMPORTANCE It is uncertain what the optimal target temperature is for targeted temperature management (TTM) in patients who are comatose following cardiac arrest. OBJECTIVE To examine whether illness severity is associated with changes in the association between target temperature and patient outcome. DESIGN, SETTING, AND PARTICIPANTS This cohort study compared outcomes for 1319 patients who were comatose after cardiac arrest at a single center in Pittsburgh, Pennsylvania, from January 2010 to December 2018. Initial illness severity was based on coma and organ failure scores, presence of severe cerebral edema, and presence of highly malignant electroencephalogram (EEG) after resuscitation. EXPOSURE TTM at 36°C or 33°C. MAIN OUTCOMES AND MEASURES Primary outcome was survival to hospital discharge, and secondary outcomes were modified Rankin Scale and cerebral performance category. RESULTS Among 1319 patients, 728 (55.2%) had TTM at 33°C (451 [62.0%] men; median [interquartile range] age, 61 [50-72] years) and 591 (44.8%) had TTM at 36°C (353 [59.7%] men; median [interquartile range] age, 59 [48-69] years). Overall, 184 of 187 patients (98.4%) with severe cerebral edema died and 234 of 243 patients (96.3%) with highly malignant EEG died regardless of TTM strategy. Comparing TTM at 33°C with TTM at 36°C in 911 patients (69.1%) with neither severe cerebral edema nor highly malignant EEG, survival was lower in patients with mild to moderate coma and no shock (risk difference,-13.8%; 95% CI,-24.4% to-3.2%) but higher in patients with mild to moderate coma and cardiopulmonary failure (risk difference, 21.8%; 95% CI, 5.4% to 38.2%) or with severe coma (risk difference, 9.7%; 95% CI, 4.0% to 15.3%). Interactions were similar for functional outcomes. Most deaths (633 of 968 [65.4%]) resulted after withdrawal of life-sustaining therapies. CONCLUSIONS AND RELEVANCE In this study, TTM at 33°C was associated with better survival than TTM at 36°C among patients with the most severe post-cardiac arrest illness but without severe cerebral edema or malignant EEG. However, TTM at 36°C was associated with better survival among patients with mild-to moderate-severity illness.
2021
Background: Transthoracic echocardiographic (TTE) indices of myocardial function among survivors of out-of-hospital cardiac arrest (OHCA) have been related to neurological outcome; however, results are inconsistent. We hypothesized that changes in average peak systolic mitral annular velocity (s’) from 24 hours (h) to 72 h following start of targeted temperature management (TTM) predict six-month neurological outcome in comatose OHCA survivors.Methods: We investigated the association between peak systolic velocity of the mitral plane (s’) and six-month neurological outcome in a population of 99 patients from a randomised controlled trial comparing TTM at 33±1°C for 24 hours (h) (n=47) vs. 48h (n=52) following OHCA (TTH48-trial). TTE was conducted at 24h, 48h, and 72h after reaching target temperature. The primary outcome was 180 days neurological outcome assessed by Cerebral Performance Category score (CPC180) and the primary TTE outcome measure was s’. Secondary outcome measures we...
Resuscitation, 2019
Introduction: Targeted temperature management (TTM) after out-of-hospital cardiac arrest (OHCA) has been recommended in international guidelines since 2005. The TTM-trial published in 2013 showed no difference in survival or neurological outcome for patients randomised to 33 C or 36 C, and many hospitals have changed practice. The optimal utilization of TTM is still debated. This study aimed to analyse if a difference in temperature goal was associated with outcome in an unselected international registry population. Methods: This is a retrospective observational study based on a prospective registrythe International Cardiac Arrest Registry 2. Patients were categorized as receiving TTM in the lower range at 32À34 C (TTM-low) or at 35À37 C (TTM-high). Primary outcome was good functional status defined as cerebral performance category (CPC) of 1À2 at hospital discharge and secondary outcome was adverse events related to TTM. A logistic
Trials, 2013
Background: Animal experimental studies and previous randomized trials suggest an improvement in mortality and neurological function with temperature regulation to hypothermia after cardiac arrest. According to a systematic review, previous trials were small, had a risk of bias, evaluated select populations, and did not treat hyperthermia in the control groups. The optimal target temperature management (TTM) strategy is not known. To prevent outcome reporting bias, selective reporting and data-driven results, we present the a priori defined detailed statistical analysis plan as an update to the previously published outline of the design and rationale for the TTM trial.