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A multicentre randomized pilot trial on the effectiveness of different levels of cooling in comatose survivors of out-of-hospital cardiac arrest: the FROST-I trial

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Abstract

Purpose

To obtain initial data on the effect of different levels of targeted temperature management (TTM) in out-of-hospital cardiac arrest (OHCA).

Methods

We designed a multicentre pilot trial with 1:1:1 randomization to either 32 °C (n = 52), 33 °C (n = 49) or 34 °C (n = 49), via endovascular cooling devices during a 24-h period in comatose survivors of witnessed OHCA and initial shockable rhythm. The primary endpoint was the percentage of subjects surviving with good neurologic outcome defined by a modified Rankin Scale (mRS) score of ≤ 3, blindly assessed at 90 days.

Results

At baseline, different proportions of patients who had received defibrillation administered by a bystander were assigned to groups of 32 °C (13.5%), 33 °C (34.7%) and 34 °C (28.6%; p = 0.03). The percentage of patients with an mRS ≤ 3 at 90 days (primary endpoint) was 65.3, 65.9 and 65.9% in patients assigned to 32, 33 and 34 °C, respectively, non-significant (NS). The multivariate Cox proportional hazards model identified two variables significantly related to the primary outcome: male gender and defibrillation by a bystander. Among the 43 patients who died before 90 days, 28 died following withdrawal of life-sustaining therapy, as follows: 7/16 (43.8%), 10/13 (76.9%) and 11/14 (78.6%) of patients assigned to 32, 33 and 34 °C, respectively (trend test p = 0.04). All levels of cooling were well tolerated.

Conclusions

There were no statistically significant differences in neurological outcomes among the different levels of TTM. However, future research should explore the efficacy of TTM at 32 °C.

Clinical trial registration

ClinicalTrials.gov unique identifier: NCT02035839 (http://clinicaltrials.gov).

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Funding

This work was supported by ZOLL Medical Corporation, Inc. (USA).

Author information

Authors and Affiliations

  1. Acute Cardiac Care Unit, Cardiology Department, Hospital Universitario La Paz, IdiPaz. CIBERCV, Paseo de La Castellana, 261, 28046, Madrid, Spain

    Esteban Lopez-de-Sa, Eduardo Armada, Maria C. Monedero & Jose L. Lopez-Sendon

  2. Cardiology Department, Hospital Universitario Gregorio Marañón. CIBERCV, Calle Dr Esquerdo, 46, 28007, Madrid, Spain

    Miriam Juarez & Manuel Martinez-Sellés

  3. Cardiology Department, Hospital Universitario de Bellvitge, Carrer Prínceps d’Espanya s/n, L’Hospitalet de Llobregat, 08902, Barcelona, Spain

    José C. Sanchez-Salado & Albert Ariza

  4. Cardiology Department, Hospital Universitario de Salamanca, Paseo de San Vicente, 58-182, 37007, Salamanca, Spain

    Pedro L. Sanchez & Aitor Uribarri

  5. Cardiology Department, Hospital Universitario Josep Trueta, Avenida França, s/n, 17007, Girona, Spain

    Pablo Loma-Osorio

  6. Intensive Cardiac Care Unit, Cardiology Department, Hospital de Sant Pau. IIB-Sant Pau. CIBERCV, Universitat Autònoma de Barcelona, Calle de San Quintín, 89, 08026, Barcelona, Spain

    Alessandro Sionis

  7. Universidad Complutense, Avenida Séneca 2, Universidad Europea, Calle Tajo s/n, Villaviciosa de Odón, 28670, Madrid, Spain

    Manuel Martinez-Sellés

  8. Intensive Care Department, Hospital Clínico San Carlos, Calle Profesor Martin Lagos, 2, 28040, Madrid, Spain

    Juán C. Martín-Benitez

  9. Cardiology Department, Complejo Hospitalario Universitario de Santiago. CIBERCV, Travesía Da Choupana S/N, Santiago de Compostela, La Coruña, 15706, Spain

    José M. Garcia-Acuña

  10. Intensive Care Department, Hospital Universitario Principe de Asturias, Carretera. Alcalá-Meco, s/n, Alcalá de Henares, 28805, Madrid, Spain

    Patricia Villa

  11. Cardiology Department, Hospital Universitario de Canarias, Calle Ofra S/N, San Cristóbal de La Laguna, 38320, Santa Cruz de Tenerife, Spain

    Pablo J. Perez

  12. Department of Internal Medicine, Nephrology and Intensive Care, Charité-Universitätsmedizin, Charitéplatz 1, 10117, Berlin, Germany

    Christian Storm

  13. Biostatistics Department, ZOLL Medical Corporation, 2000 Ringwood Ave, San Jose, CA, 95131, USA

    Anne Dee

Authors
  1. Esteban Lopez-de-Sa
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  2. Miriam Juarez
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  3. Eduardo Armada
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  4. José C. Sanchez-Salado
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  5. Pedro L. Sanchez
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  6. Pablo Loma-Osorio
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  7. Alessandro Sionis
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  8. Maria C. Monedero
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  9. Manuel Martinez-Sellés
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  10. Juán C. Martín-Benitez
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  11. Albert Ariza
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  12. Aitor Uribarri
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  13. José M. Garcia-Acuña
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  14. Patricia Villa
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  15. Pablo J. Perez
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  16. Christian Storm
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  17. Anne Dee
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  18. Jose L. Lopez-Sendon
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Corresponding author

Correspondence to Esteban Lopez-de-Sa.

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Conflict of interest

E. Lopez-de-Sa: Research Grant; Modest; ZOLL Medical Corporation, Inc. (USA), Boehringer Ingelheim, Servier. Speakers Bureau; Modest; Daiichi Sankyo, Rovi, Servier, BARD. Consultant/Advisory Board; Modest; AstraZeneca. M. Juarez: Research Grant; Modest; ZOLL Medical Corporation, Inc. (USA). E. Armada: Research Grant; Modest; ZOLL Medical Corporation, Inc. (USA). J.C. Sanchez-Salado: None. P.L. Sanchez: None. P. Loma-Osorio: Research Grant; Modest; ZOLL Medical Corporation, Inc. (USA), Sanofi. Honoraria; Modest; Sanofi, Daiichi Sankyo, AstraZeneca, Pfizer. A. Sionis: None. M.C. Monedero: Research Grant; Modest; ZOLL Medical Corporation, Inc. (USA), Lilly. M. Martinez-Selles: Research Grant; Modest; ZOLL Medical Corporation, Inc. (USA). M. Sanchez-Gracia: None. A. Ariza: Research Grant; Modest; ZOLL Medical Corporation, Inc. (USA). A. Uribarri: Research Grant; Modest; ZOLL Medical Corporation, Inc. (USA). J.M. Garcia-Acuña: None. P. Villa: None. P.J. Perez: Research Grant; Modest; ZOLL Medical Corporation, Inc. (USA). C. Storm: Research Grant; Significant; Fresenius Deutschland. Speakers Bureau; Modest; Philips, C.R. BARD, ZOLL Medical Corporation, Inc., Medivance, Covidien, Nonin Medical, German Heart Foundation. A. Dee: Employment; Significant; ZOLL Medical Corporation, Inc. J.L. Lopez-Sendon: Research Grant: Modest; Sanofi, Servier, AstraZeneca, GlaxoSmithKline, Menarini, Novartis. Consultant/Advisory Board; Modest; Boehringer Ingelheim, Daiichi Sankyo. Other; Modest; Servier.

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Lopez-de-Sa, E., Juarez, M., Armada, E. et al. A multicentre randomized pilot trial on the effectiveness of different levels of cooling in comatose survivors of out-of-hospital cardiac arrest: the FROST-I trial. Intensive Care Med 44, 1807–1815 (2018). https://doi.org/10.1007/s00134-018-5256-z

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  • DOI: https://doi.org/10.1007/s00134-018-5256-z

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