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Therapeutic hypothermia after nonshockable cardiac arrest: the HYPERION multicenter, randomized, controlled, assessor-blinded, superiority trial.

Lascarrou JB, Meziani F, Le Gouge A, Boulain T, Bousser J, Belliard G, Asfar P, Frat JP, Dequin PF, Gouello JP, Delahaye A, Hssain AA, Chakarian JC, Pichon N, Desachy A, Bellec F, Thevenin D, Quenot JP, Sirodot M, Labadie F, Plantefeve G, Vivier D, Girardie P, Giraudeau B, Reignier J, Clinical Research in Intensive Care and Sepsis (CRICS) Group and HYPERION Study Gro - Scand J Trauma Resusc Emerg Med (2015)

Bottom Line: The primary outcome is day-90 neurological status assessed by the Cerebral Performance Categories (CPC) Scale with dichotomization of the results (1 + 2 versus 3 + 4 + 5).Secondary outcomes are day-90 mortality, hospital mortality, severe adverse events, infections, and neurocognitive performance.Two interim analyses will be performed, after inclusion of 200 and 400 patients, respectively.

View Article: PubMed Central - PubMed

Affiliation: Medical-Surgical Intensive Care Unit, District Hospital Center, La Roche-sur-Yon, France. jean-baptiste.lascarrou@chd-vendee.fr.

ABSTRACT

Background: Meta-analyses of nonrandomized studies have provided conflicting data on therapeutic hypothermia, or targeted temperature management (TTM), at 33°C in patients successfully resuscitated after nonshockable cardiac arrest. Nevertheless, the latest recommendations issued by the International Liaison Committee on Resuscitation and by the European Resuscitation Council recommend therapeutic hypothermia. New data are available on the adverse effects of therapeutic hypothermia, notably infectious complications. The risk/benefit ratio of therapeutic hypothermia after nonshockable cardiac arrest is unclear.

Methods: HYPERION is a multicenter (22 French ICUs) trial with blinded outcome assessment in which 584 patients with successfully resuscitated nonshockable cardiac arrest are allocated at random to either TTM between 32.5 and 33.5°C (therapeutic hypothermia) or TTM between 36.5 and 37.5°C (therapeutic normothermia) for 24 hours. Both groups are managed with therapeutic normothermia for the next 24 hours. TTM is achieved using locally available equipment. The primary outcome is day-90 neurological status assessed by the Cerebral Performance Categories (CPC) Scale with dichotomization of the results (1 + 2 versus 3 + 4 + 5). The primary outcome is assessed by a blinded psychologist during a semi-structured telephone interview of the patient or next of kin. Secondary outcomes are day-90 mortality, hospital mortality, severe adverse events, infections, and neurocognitive performance. The planned sample size of 584 patients will enable us to detect a 9% absolute difference in day-90 neurological status with 80% power, assuming a 14% event rate in the control group and a two-sided Type 1 error rate of 4.9%. Two interim analyses will be performed, after inclusion of 200 and 400 patients, respectively.

Discussion: The HYPERION trial is a multicenter, randomized, controlled, assessor-blinded, superiority trial that may provide an answer to an issue of everyday relevance, namely, whether TTM is beneficial in comatose patients resuscitated after nonshockable cardiac arrest. Furthermore, it will provide new data on the tolerance and adverse events (especially infectious complications) of TTM at 32.5-33.5°C.

Trial registration: ClinicalTrials.gov: NCT01994772 .

No MeSH data available.


Related in: MedlinePlus

Benefits from targeted temperature management in relation to patient’s prognosis documented in previous studies and expected in the HYPERION trial.
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Fig4: Benefits from targeted temperature management in relation to patient’s prognosis documented in previous studies and expected in the HYPERION trial.

Mentions: Few data are available to explain the discrepancies among the findings from trials of TTM, most notably in patients with nonshockable cardiac arrest. The beneficial effects of 32.5°-33.5° TTM probably vary with the degree of brain damage at treatment initiation. The ischemic penumbra concept developed for stroke is probably applicable to the brain damage seen after cardiac arrest. In a study of patients with nonshockable cardiac arrest, the benefits from 32.5°-33.5° TTM were greatest when the no-flow time was longer than 8 minutes [76]. Similarly, in another study of patients with shockable or nonshockable cardiac arrest, 32.5°-33.5° TTM was most effective in the subgroup whose time from cardiac arrest to the return of spontaneous circulation (ROSC) was longer than 15 minutes [74]. In a previous pilot study, 32° was better than 34° as the target temperature [77]. The TTM Trial published in The New England Journal Medicine [19] showed that TTM at 36°C was similar to TTM at 33°C in patients with good prognostic factors including witnessed cardiac arrest in shockable rhythm with short no-flow and low-flow times compared to patients enrolled in earlier trials and having less favorable prognostic characteristics [7,8]. Figure 3 reports the estimated benefits of TTM and Figure 4 the effects documented in previous studies and the expected effects in the HYPERION trial.Figure 3


Therapeutic hypothermia after nonshockable cardiac arrest: the HYPERION multicenter, randomized, controlled, assessor-blinded, superiority trial.

Lascarrou JB, Meziani F, Le Gouge A, Boulain T, Bousser J, Belliard G, Asfar P, Frat JP, Dequin PF, Gouello JP, Delahaye A, Hssain AA, Chakarian JC, Pichon N, Desachy A, Bellec F, Thevenin D, Quenot JP, Sirodot M, Labadie F, Plantefeve G, Vivier D, Girardie P, Giraudeau B, Reignier J, Clinical Research in Intensive Care and Sepsis (CRICS) Group and HYPERION Study Gro - Scand J Trauma Resusc Emerg Med (2015)

Benefits from targeted temperature management in relation to patient’s prognosis documented in previous studies and expected in the HYPERION trial.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4353458&req=5

Fig4: Benefits from targeted temperature management in relation to patient’s prognosis documented in previous studies and expected in the HYPERION trial.
Mentions: Few data are available to explain the discrepancies among the findings from trials of TTM, most notably in patients with nonshockable cardiac arrest. The beneficial effects of 32.5°-33.5° TTM probably vary with the degree of brain damage at treatment initiation. The ischemic penumbra concept developed for stroke is probably applicable to the brain damage seen after cardiac arrest. In a study of patients with nonshockable cardiac arrest, the benefits from 32.5°-33.5° TTM were greatest when the no-flow time was longer than 8 minutes [76]. Similarly, in another study of patients with shockable or nonshockable cardiac arrest, 32.5°-33.5° TTM was most effective in the subgroup whose time from cardiac arrest to the return of spontaneous circulation (ROSC) was longer than 15 minutes [74]. In a previous pilot study, 32° was better than 34° as the target temperature [77]. The TTM Trial published in The New England Journal Medicine [19] showed that TTM at 36°C was similar to TTM at 33°C in patients with good prognostic factors including witnessed cardiac arrest in shockable rhythm with short no-flow and low-flow times compared to patients enrolled in earlier trials and having less favorable prognostic characteristics [7,8]. Figure 3 reports the estimated benefits of TTM and Figure 4 the effects documented in previous studies and the expected effects in the HYPERION trial.Figure 3

Bottom Line: The primary outcome is day-90 neurological status assessed by the Cerebral Performance Categories (CPC) Scale with dichotomization of the results (1 + 2 versus 3 + 4 + 5).Secondary outcomes are day-90 mortality, hospital mortality, severe adverse events, infections, and neurocognitive performance.Two interim analyses will be performed, after inclusion of 200 and 400 patients, respectively.

View Article: PubMed Central - PubMed

Affiliation: Medical-Surgical Intensive Care Unit, District Hospital Center, La Roche-sur-Yon, France. jean-baptiste.lascarrou@chd-vendee.fr.

ABSTRACT

Background: Meta-analyses of nonrandomized studies have provided conflicting data on therapeutic hypothermia, or targeted temperature management (TTM), at 33°C in patients successfully resuscitated after nonshockable cardiac arrest. Nevertheless, the latest recommendations issued by the International Liaison Committee on Resuscitation and by the European Resuscitation Council recommend therapeutic hypothermia. New data are available on the adverse effects of therapeutic hypothermia, notably infectious complications. The risk/benefit ratio of therapeutic hypothermia after nonshockable cardiac arrest is unclear.

Methods: HYPERION is a multicenter (22 French ICUs) trial with blinded outcome assessment in which 584 patients with successfully resuscitated nonshockable cardiac arrest are allocated at random to either TTM between 32.5 and 33.5°C (therapeutic hypothermia) or TTM between 36.5 and 37.5°C (therapeutic normothermia) for 24 hours. Both groups are managed with therapeutic normothermia for the next 24 hours. TTM is achieved using locally available equipment. The primary outcome is day-90 neurological status assessed by the Cerebral Performance Categories (CPC) Scale with dichotomization of the results (1 + 2 versus 3 + 4 + 5). The primary outcome is assessed by a blinded psychologist during a semi-structured telephone interview of the patient or next of kin. Secondary outcomes are day-90 mortality, hospital mortality, severe adverse events, infections, and neurocognitive performance. The planned sample size of 584 patients will enable us to detect a 9% absolute difference in day-90 neurological status with 80% power, assuming a 14% event rate in the control group and a two-sided Type 1 error rate of 4.9%. Two interim analyses will be performed, after inclusion of 200 and 400 patients, respectively.

Discussion: The HYPERION trial is a multicenter, randomized, controlled, assessor-blinded, superiority trial that may provide an answer to an issue of everyday relevance, namely, whether TTM is beneficial in comatose patients resuscitated after nonshockable cardiac arrest. Furthermore, it will provide new data on the tolerance and adverse events (especially infectious complications) of TTM at 32.5-33.5°C.

Trial registration: ClinicalTrials.gov: NCT01994772 .

No MeSH data available.


Related in: MedlinePlus