Clinical trial NCT01722422: Hyperoxia and Hypertonic Saline in Septic Shock
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Septic Shock
Adult Respiratory Distress Syndrome
Keywords: sepsis
shock
hyperoxia
hypertonic saline
Lead sponsor: University Hospital, Angers
Sponsor class: OTHER_GOV
First posted: 2012-11-06
Enrollment: 441
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: TREATMENT

Brief summary: Assessment of the effect of hyperoxia and hypertonic saline on survival in patients with septic shock Hyperoxia and hypertonic saline may have beneficial effects on organ perfusion and oxygenation and may reduce the organ failure occurences. To date, only scarce data are available. Side effects are not well described. Therefore we designed a randomized clinical trial in order to assess the early administration of hypertonic saline and oxygen in the very early beginning of septic shock.

Detailed description: The study is designed as factorial 2x2. Patients will be stratified at the randomisation according the presence or absence of Acute Respiratory Distress Syndrome in order to perform a sub group analysis for all outcome criteria.

Eligibility criteria: Inclusion Criteria:

* patients with less than 6 hours septic shock according criteria of Bone
* minimal dose of catecholamines at least 0.1 µg/Kg/min
* patient with mechanical ventilation
* written informed consent

Exclusion Criteria:

* age \< 18 years
* pregnancy
* participation in other trial with the same endpoint
* moribund
* absence of registration in french health care system
* patient protected by law
* hypernatremia \< 130 mmol/l ou \> 145 mmol/l
* patient with P/F \< 100 mm Hg with PEEP \> 5 cms of water
* intracranial hypertension
* patient admitted for cardiac arrest
* overt cardiac failure

Primary outcomes:
measure: all-cause mortality
timeFrame: day 28
Secondary outcomes:
measure: all-cause mortality
timeFrame: day 90
measure: evolution of organ failures
timeFrame: day 1 to day 28
measure: catecholamines free days
timeFrame: day 1 to day 28
measure: mechanical ventilation free days
timeFrame: day 1 to day 28
measure: safety data
timeFrame: day 1 to day 90
Other outcomes:
Locations:
city: Angers
country: France
facility: University Hospital Angers
Study officials:
References:
citation: Calzia E, Asfar P, Hauser B, Matejovic M, Ballestra C, Radermacher P, Georgieff M. Hyperoxia may be beneficial. Crit Care Med. 2010 Oct;38(10 Suppl):S559-68. doi: 10.1097/CCM.0b013e3181f1fe70.
citation: Goertz AW, Mehl T, Lindner KH, Rockemann MG, Schirmer U, Schwilk B, Georgieff M. Effect of 7.2% hypertonic saline/6% hetastarch on left ventricular contractility in anesthetized humans. Anesthesiology. 1995 Jun;82(6):1389-95. doi: 10.1097/00000542-199506000-00010.
citation: Oliveira RP, Weingartner R, Ribas EO, Moraes RS, Friedman G. Acute haemodynamic effects of a hypertonic saline/dextran solution in stable patients with severe sepsis. Intensive Care Med. 2002 Nov;28(11):1574-81. doi: 10.1007/s00134-002-1509-x. Epub 2002 Oct 1.
citation: Junger WG, Hoyt DB, Davis RE, Herdon-Remelius C, Namiki S, Junger H, Loomis W, Altman A. Hypertonicity regulates the function of human neutrophils by modulating chemoattractant receptor signaling and activating mitogen-activated protein kinase p38. J Clin Invest. 1998 Jun 15;101(12):2768-79. doi: 10.1172/JCI1354.
citation: Coimbra R, Hoyt DB, Junger WG, Angle N, Wolf P, Loomis W, Evers MF. Hypertonic saline resuscitation decreases susceptibility to sepsis after hemorrhagic shock. J Trauma. 1997 Apr;42(4):602-6; discussion 606-7. doi: 10.1097/00005373-199704000-00004.
citation: Commereuc M, Nevoret C, Radermacher P, Katsahian S, Asfar P, Schortgen F; HYPER2S investigators. Hyperchloremia is not associated with AKI or death in septic shock patients: results of a post hoc analysis of the "HYPER2S" trial. Ann Intensive Care. 2019 Aug 22;9(1):95. doi: 10.1186/s13613-019-0570-3.
citation: Asfar P, Schortgen F, Boisrame-Helms J, Charpentier J, Guerot E, Megarbane B, Grimaldi D, Grelon F, Anguel N, Lasocki S, Henry-Lagarrigue M, Gonzalez F, Legay F, Guitton C, Schenck M, Doise JM, Devaquet J, Van Der Linden T, Chatellier D, Rigaud JP, Dellamonica J, Tamion F, Meziani F, Mercat A, Dreyfuss D, Seegers V, Radermacher P; HYPER2S Investigators; REVA research network. Hyperoxia and hypertonic saline in patients with septic shock (HYPERS2S): a two-by-two factorial, multicentre, randomised, clinical trial. Lancet Respir Med. 2017 Mar;5(3):180-190. doi: 10.1016/S2213-2600(17)30046-2. Epub 2017 Feb 15.