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Trials
Published in: Trials 1/2016

Open Access 01-12-2016 | Study protocol

Targeted tissue perfusion versus macrocirculation-guided standard care in patients with septic shock (TARTARE-2S): study protocol and statistical analysis plan for a randomized controlled trial

Authors: Ville Pettilä, Tobias Merz, Erika Wilkman, Anders Perner, Sari Karlsson, Theis Lange, Johanna Hästbacka, Peter Buhl Hjortrup, Anne Kuitunen, Stephan M. Jakob, Jukka Takala

Published in: Trials | Issue 1/2016

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Abstract

Background

Septic shock has a 90-day mortality risk of up to 50 %. The hemodynamic targets, including mean arterial pressure (MAP) are not based on robust clinical data. Both severe hypotension and high doses of vasopressors may be harmful. Hence, re-evaluation of hemodynamic targets in septic shock is relevant.

Methods/design

The targeted tissue perfusion versus macrocirculation-guided standard care in patients with septic shock (TARTARE-2S) trial is a prospective, two-parallel-group, randomized, open-label, multicenter trial with assessor-blinded outcome evaluation. We will randomize at least 200 patients with septic shock in four European intensive care units (ICUs) to test whether a tissue perfusion-guided treatment strategy based on capillary refill time, peripheral temperature, arterial lactate concentrations, and accepting lower MAP levels, leads to a faster resolution of shock than macrocirculation target-guided standard care.
The primary outcome measure is days alive in 30 days with normal arterial blood lactate (first value of <2 mmol/L) and without any inotropic or vasopressor agent. Secondary outcomes include individual components of the primary outcome, days alive without renal replacement, days alive without mechanical ventilation in 30 days, and new acute kidney injury. The sample size enables detection of a 13.5-h difference in the primary outcome with a type 1 error of 5 % and power of 80 %, assuming 25 % mortality and a mean of 650 h (SD 30) among the 30-day survivors. After 150 included patients the statistician masked for allocation group will recalculate the sample size potentially increasing the sample up to 300. The Data Safety and Monitoring Board (DSMB) will review the safety data after 100 patients.

Discussion

The TARTARE-2S trial will provide important clinical data on treatment targets in septic shock, evaluating the impact of clinical tissue perfusion-guided hemodynamic treatment on a surrogate outcome combining resolution of shock (hyperlactatemia and vasopressors/inotropes), and 30-day mortality.

Trial registration

ClinicalTrials.gov: NCT02579525. Registered on 19 October 2015.
Appendix
Available only for authorised users
Literature
1.
The ARISE investigators, ANZICS Clinical Trials Group, Peake SL, Delaney A, Bailey M, Bellomo R, et al. Goal-directed resuscitation for patients with early septic shock. N Engl J Med. 2014;371:1496–506.CrossRef
2.
Holst LB, the TRISS Trial Group and the Scandinavian Critical Care Trials Group, Haase N, Wetterslev J, Wernerman J, Guttormsen AB, Karlsson S, et al. Lower versus higher hemoglobin threshold for transfusion in septic shock. N Engl J Med. 2014;371:1381–91.CrossRefPubMed
3.
4.
Investigators PCESS, Yealy DM, Kellum JA, Huang DT, Barnato AE, Weissfeld LA, et al. Protocol-based care for early septic shock. N Engl J Med. 2014;371:1683–93.CrossRef
5.
Mouncey PR, Osborn TM, Power GS, Harrison DA, Sadique MZ, Grieve RD, Investigators PMIST, et al. Trial for early, goal-directed therapy in septic shock. N Engl J Med. 2015;372:1301–11.CrossRefPubMed
6.
Rivers E, Nguyen B, Havstad S, Ressler J, Muzzin A, Knoblich B. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med. 2001;345:1368–77.CrossRefPubMed
7.
Dellinger RP, Levy MM, Rhodes A, Annane D, Gerlach H, Opal SM, et al. Surviving Sepsis Campaign: International Guidelines for Management of Severe Sepsis and Septic Shock, 2012. Intensive Care Med. 2013;39:165–228.CrossRefPubMed
8.
Dünser MW, Ruokonen E, Pettilä V, Ulmer H, Torgersen C, Schmittinger CA, et al. Association of arterial blood pressure and vasopressor load with septic shock mortality: a post hoc analysis of a multicenter trial. Crit Care. 2009;13:R181.CrossRefPubMedPubMedCentral
9.
D’Aragon F, Belley-Cote EP, Meade MO, Lauzier F, Adhikari NK, Briel M, Group CCCT, et al. Blood pressure targets for vasopressor therapy: a systematic review. Shock. 2015;43:530–9.CrossRefPubMed
10.
Bakker J, Gris P, Coffernils M, Kahn RJ, Vincent JL. Serial blood lactate levels can predict development of multiple organ failure following septic shock. Am J Surg. 1996;171:2221–6.CrossRef
11.
Nguyen HB, Loomba M, Yang JJ, Jacobsen G, Shah K, Otero RM, et al. Early lactate clearance is associated with biomarkers of inflammation, coagulation, apoptosis, organ dysfunction and mortality in severe sepsis and septic shock. J Inflamm. 2010;7:6.CrossRef
12.
Nichol A, Egi M, Pettilä V, Bellomo R, French G, Hart G, et al. Relative hyperlactatemia and hospital mortality in critically ill patients: a retrospective multi-centre study. Crit Care. 2010;14:R25.CrossRefPubMedPubMedCentral
13.
Lima A, Jansen TC, van Bommel J, Ince C, Bakker J. The prognostic value of the subjective assessment of peripheral perfusion in critically ill patients. Crit Care Med. 2009;37:934–8.CrossRefPubMed
14.
Jones AE, Shapiro NI, Trzeciak S, Arnol RC, Claremont HA, Kline JA, Emergency Medicine Shock Research Network (EMShockNet) Investigators. Lactate clearance vs central venous oxygen saturation as goals of early sepsis therapy: a randomized clinical trial. JAMA. 2010;303:739–46.CrossRefPubMedPubMedCentral
15.
Lima A, Jansen TC, van Bommel J, Ince C, Bakker J. The prognostic value of subjective assessment of peripheral perfusion in critically ill patients. Crit Care Med. 2009;37:934–8.CrossRefPubMed
16.
Lima A, van Bommel J, Sikorska K, van Genderen M, Klijn E, Lesaffre E, et al. The relation of near-infrared spectroscopy with changes in peripheral circulation in critically ill patients. Crit Care Med. 2011;39:1649–54.CrossRefPubMed
17.
Ait-Oufella H, Lemoinne S, Boelle PY, Galbois A, Baudel JL, Lemant J, et al. Mottling score predicts survival in septic shock. Intensive Care Med. 2011;37:801–7.CrossRefPubMed
18.
Pettilä V, Bellomo R. Understanding acute kidney injury in sepsis. Intensive Care Med. 2014;40:1018–20.CrossRefPubMed
19.
Smith OM, Wald R, Adhikari NK, Pope K, Weir MA, Bagshaw SM, Canadian Critical Care Trials Group. Standard versus accelerated initiation of renal replacement therapy in acute kidney injury (STARRT-AKI): study protocol for a randomized controlled trial. Trials. 2013;14:320.CrossRefPubMedPubMedCentral
20.
Vaara S, Reinikainen M, Wald R, Bagshaw S, Pettilä V, The FINNAKI Group. Timing of RRT based on the presence of conventional indications. Clin J Am Soc Nephrol. 2014;9:1577–85.CrossRefPubMedPubMedCentral
21.
Wald R, Adhikari NK, Smith OM, Weir MA, Pope K, Cohen A, et al. Comparison of standard and accelerated initiation of renal replacement therapy in acute kidney injury. Kidney Int. 2015;88:897–904.CrossRefPubMed
22.
Dünser MW, Takala J, Ulmer H, Mayr VD, Luckner G, Jochberger S, et al. Arterial blood pressure during early sepsis and outcome. Intensive Care Med. 2009;35:1225–33.CrossRefPubMed
23.
Poukkanen M, Wilkman E, Vaara ST, Pettilä V, Kaukonen KM, Korhonen AM, et al. Hemodynamic variables and progression of acute kidney injury in critically ill patients with severe sepsis. Data from the prospective observational FINNAKI study. Crit Care. 2013;17:R295.CrossRefPubMedPubMedCentral
24.
Raimundo M, Crichton S, Syed Y, Martin JR, Beale R, Teacher D, et al. Low systemic oxygen delivery and BP and risk of progression of AKI. Clin J Am Soc Nephrol. 2015;10:1340–9.CrossRefPubMed
25.
Cecconi M, Hofer C, Teboul JL, Pettilä V, Wilkman E, Molnar Z, FENICE investigators and the ESICM Trial Group, et al. Fluid challenges in intensive care: The FENICE study: a global inception cohort study. Intensive Care Med. 2015;41:1529–37.CrossRefPubMedPubMedCentral
26.
Perner A, Haase N, Guttormsen AB, Tenhunen J, Klemenzson G, Aneman Å, Wetterslev J, 6S Trial Group and Scandinavian Critical Care Trials Group, et al. Hydroxyethyl starch 130/0.42 versus Ringer’s acetate in severe sepsis. N Engl J Med. 2012;67:124–34.CrossRef
27.
Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, et al. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. 2016;315:801–10.CrossRefPubMed
28.
Iwashyna TJ, Burke JF, Sussman JB, Prescott HC, Hayward RA, Angus DC. Implications of heterogeneity of treatment effect for reporting and analysis of randomized trials in critical care. Am J Respir Crit Care Med. 2015;192:1045–51.CrossRefPubMed
Metadata
Title
Targeted tissue perfusion versus macrocirculation-guided standard care in patients with septic shock (TARTARE-2S): study protocol and statistical analysis plan for a randomized controlled trial
Authors
Ville Pettilä
Tobias Merz
Erika Wilkman
Anders Perner
Sari Karlsson
Theis Lange
Johanna Hästbacka
Peter Buhl Hjortrup
Anne Kuitunen
Stephan M. Jakob
Jukka Takala
Publication date
01-12-2016
Publisher
BioMed Central
Published in
Trials / Issue 1/2016
Electronic ISSN: 1745-6215
DOI
https://doi.org/10.1186/s13063-016-1515-x

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