Clinical trial NCT03632837: HaemoAdsorption Nach Reanimation An ECMO
Official title: HaemoAdsorption Nach Reanimation An ECMO
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Cardiac Arrest
Resuscitation
Inflammation
Multi-Organ Disorder
Keywords: extracorporal circulation
hemoadsorption
post resuscitation syndrome
Lead sponsor: Universitätsklinikum Hamburg-Eppendorf
Sponsor class: OTHER
Collaborators: name: CytoSorbents Corporation and CytoSorbents Medical Inc.
First posted: 2018-08-16
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study evaluates the use of an additional hemoadsorption device in adult patients undergoing veno-arterial extracorporal membrane oxygenation (ECMO) following cardiac arrest and cardiopulmonary resuscitation in respect to its effects on post resuscitation inflammatory syndrome.

At implantation of the ECMO the participants are going to be randomized into a treatment and a control group. The first will be outfitted with a polymer-based adsorption device implemented in the extracorporal circulation established by ECMO for 48h, the control group is going to be treated by ECMO and standard intensive care alone. To detect any significant differences in terms of inflammatory response and patient outcome the investigators will regularly determine the blood levels of certain cytokines in fixed intervalls. In addition, the investigators are going to compare secondary clinical outcome parameters like organ disfunction and 30d mortality.

Detailed description: Even after successful return of spontaneus circulation (ROSC), patients suffering a cardiac arrest with subsequent cardipulmonary resuscitation (CPR) are still facing a significant morbidity and mortality in the post-resuscitation phase. They are nowadays often subjected to extracorporal membrane oxygenation (ECMO), supplementing or even replacing cardiac and/or pulmonary function for a certain period in order to reduce the workload for these critical organs. However, as well as the initial ischemia/reperfusion damage, subsequent procedures create significant stress to the patients organism, causing severe inflammation and contributing to post-resuscitation single or multiple organ disfunction and/or failure.

Continously eliminating relevant mediators of inflammation by adsorption to a polymer-based material in extracorporal circulation has been shown to influence the course of this inflammatory syndrome in patients with severe infection and sepsis. Any relevant clinical studies evaluating the use of such a device in post-resuscitation care are still lacking, yet.

Therefore, in this study the investigators are going to test the hypothesis that such a device is capable of significantly altering the cytokine levels during and even shortly after a 48h treatment period in addition to the standard ECMO therapy all patients are going to receive. As a secondary outlook, the investigators are going to compare the clinical outcome of the patients in terms of major organ disfunction and overall 30d mortality.

At the time extracoporal circulation is established during or after CPR, all participants (n=40) are enrolled and randomized into a treatment and a control group. The extracorporal circulation over the ECMO device is then outfitted with a certified in line adsorption cartridge for the treatment group. Due to technical reasons, this cartridge has to be exchanged for another identical module after 24h of continuous treatment. Adsorption therapy is terminated after 48h. The control group is subjected to ECMO without any additional modules. Both groups are receiving standard intensive care during the course of the study. All diagnostic and therapeutic decisions with the exemption of those directly concerning the hemoadsorption and sampling protocol are at sole discretion of the clinical staff.

For both groups, blood samples are taken at time points 0,6,12,24,36,48,72h after establishment of ECMO or time of death, respectively. Relevant parameters are then determined in different diagnostic and research laboratories with/without sample preprocessing by the study personal in accordance with preanalytic requirements. All relevant clinical data is extracted from the digital patient data management system (PDMS).

Eligibility criteria: All patients receiving a veno-arterial ECMO after cardiac arrest at the study site are eligible for the study. Thus, the criteria are defined by the SOP "ECMO bei Reanimation" of the University Heart Center Hamburg:

Inclusion Criteria:

* observed cardiac arrest with initial hyperdynamic rhythm and sufficient primary resuscitation

Exclusion Criteria (absolute):

* existing "do-not-resuscitate"-order from the patient/a priori palliative situation
* severe trauma
* severe acute bleeding due to any cause
* confirmed or highly likely relevant and severe persistent neurologic impairment
* severe limiting comorbidities with independent and relevant reduction of life expectancy (e.g. malignoma, preexistent heart failure syndrome, obstructive/restrictive lung disease, hepatic cirrhosis)

Exclusion Criteria (relative, at the discretion of the responsible provider):

* severe initial lacacidosis
* prolongued mechanical resuscitation (\>30min)

Primary outcomes:
measure: IL-6 at hour 6
timeFrame: 6 hours post establishment of extracorporal membrane oxygenation (ECMO)
measure: IL-6 at hour 12
timeFrame: 12 hours post establishment of extracorporal membrane oxygenation (ECMO)
measure: IL-6 at hour 24
timeFrame: 24 hours post establishment of extracorporal membrane oxygenation (ECMO)
measure: IL-6 at hour 48
timeFrame: 48 hours post establishment of extracorporal membrane oxygenation (ECMO)
measure: IL-6 at hour 72
timeFrame: 72 hours post establishment of extracorporal membrane oxygenation (ECMO)
measure: TNF-a at hour 6
timeFrame: 6 hours post establishment of extracorporal membrane oxygenation (ECMO)
measure: TNF-a at hour 12
timeFrame: 12 hours post establishment of extracorporal membrane oxygenation (ECMO)
measure: TNF-a at hour 24
timeFrame: 24 hours post establishment of extracorporal membrane oxygenation (ECMO)
measure: TNF-a at hour 48
timeFrame: 48 hours post establishment of extracorporal membrane oxygenation (ECMO)
measure: TNF-a at hour 72
timeFrame: 72 hours post establishment of extracorporal membrane oxygenation (ECMO)
Secondary outcomes:
measure: S1P
timeFrame: at hours 0,6,12,24,48,72 post establishment of extracorporal membrane oxygenation (ECMO)
measure: PCT
timeFrame: at hours 0,6,12,24,48,72 post establishment of extracorporal membrane oxygenation (ECMO)
measure: CRP
timeFrame: at hours 0,6,12,24,48,72 post establishment of extracorporal membrane oxygenation (ECMO)
measure: Leukocytes
timeFrame: at hours 0,6,12,24,48,72 post establishment of extracorporal membrane oxygenation (ECMO)
measure: BNP
timeFrame: at hours 0,6,12,24,48,72 post establishment of extracorporal membrane oxygenation (ECMO)
measure: Mean arterial pressure (MAP)
timeFrame: Continuosly from enrollment to 72h post.
measure: Heart rate (HR)
timeFrame: Continuosly from enrollment to 72h post.
measure: Central venous pressure (CVP)
timeFrame: Continuosly from enrollment to 72h post.
measure: haemodynamically relevant medication
timeFrame: Continuosly from enrollment to 72h post.
measure: Trop
timeFrame: at hours 0,6,12,24,48,72 post establishment of extracorporal membrane oxygenation (ECMO)
measure: CK
timeFrame: at hours 0,6,12,24,48,72 post establishment of extracorporal membrane oxygenation (ECMO)
measure: Myoglobine
timeFrame: at hours 0,6,12,24,48,72 post establishment of extracorporal membrane oxygenation (ECMO)
measure: Hemoglobine
timeFrame: at hours 0,6,12,24,48,72 post establishment of extracorporal membrane oxygenation (ECMO)
measure: Haptoglobine
timeFrame: at hours 0,6,12,24,48,72 post establishment of extracorporal membrane oxygenation (ECMO)
measure: paO2
timeFrame: at hours 0,6,12,24,48,72 post establishment of extracorporal membrane oxygenation (ECMO)
measure: paCO2
timeFrame: at hours 0,6,12,24,48,72 post establishment of extracorporal membrane oxygenation (ECMO)
measure: SaO2
timeFrame: at hours 0,6,12,24,48,72 post establishment of extracorporal membrane oxygenation (ECMO)
measure: SvO2
timeFrame: at hours 0,6,12,24,48,72 post establishment of extracorporal membrane oxygenation (ECMO)
measure: Horowitz index
timeFrame: at hours 0,6,12,24,48,72 post establishment of extracorporal membrane oxygenation (ECMO)
measure: pH
timeFrame: at hours 0,6,12,24,48,72 post establishment of extracorporal membrane oxygenation (ECMO)
measure: HCO3
timeFrame: at hours 0,6,12,24,48,72 post establishment of extracorporal membrane oxygenation (ECMO)
measure: BE
timeFrame: at hours 0,6,12,24,48,72 post establishment of extracorporal membrane oxygenation (ECMO)
measure: N
timeFrame: at hours 0,6,12,24,48,72 post establishment of extracorporal membrane oxygenation (ECMO)
measure: K
timeFrame: at hours 0,6,12,24,48,72 post establishment of extracorporal membrane oxygenation (ECMO)
measure: C
timeFrame: at hours 0,6,12,24,48,72 post establishment of extracorporal membrane oxygenation (ECMO)
measure: Lactate
timeFrame: at hours 0,6,12,24,48,72 post establishment of extracorporal membrane oxygenation (ECMO)
measure: Mode of Ventilation
timeFrame: at hours 0,6,12,24,48,72 post establishment of extracorporal membrane oxygenation (ECMO)
measure: FiO2
timeFrame: at hours 0,6,12,24,48,72 post establishment of extracorporal membrane oxygenation (ECMO)
measure: Peak inspiratory pressure (pmax)
timeFrame: at hours 0,6,12,24,48,72 post establishment of extracorporal membrane oxygenation (ECMO)
measure: PEEP
timeFrame: at hours 0,6,12,24,48,72 post establishment of extracorporal membrane oxygenation (ECMO)
measure: Ventilation frequency
timeFrame: at hours 0,6,12,24,48,72 post establishment of extracorporal membrane oxygenation (ECMO)
measure: Tidal volume
timeFrame: at hours 0,6,12,24,48,72 post establishment of extracorporal membrane oxygenation (ECMO)
measure: Total minute ventilation
timeFrame: at hours 0,6,12,24,48,72 post establishment of extracorporal membrane oxygenation (ECMO)
measure: Complicance
timeFrame: at hours 0,6,12,24,48,72 post establishment of extracorporal membrane oxygenation (ECMO)
measure: ASAT
timeFrame: at hours 0,6,12,24,48,72 post establishment of extracorporal membrane oxygenation (ECMO)
measure: ALAT
timeFrame: at hours 0,6,12,24,48,72 post establishment of extracorporal membrane oxygenation (ECMO)
measure: INR
timeFrame: at hours 0,6,12,24,48,72 post establishment of extracorporal membrane oxygenation (ECMO)
measure: apTT
timeFrame: at hours 0,6,12,24,48,72 post establishment of extracorporal membrane oxygenation (ECMO)
measure: Crea
timeFrame: at hours 0,6,12,24,48,72 post establishment of extracorporal membrane oxygenation (ECMO)
measure: eGFR
timeFrame: at hours 0,6,12,24,48,72 post establishment of extracorporal membrane oxygenation (ECMO)
measure: Volume status
timeFrame: at hours 0,6,12,24,48,72 post establishment of extracorporal membrane oxygenation (ECMO)
measure: NSE
timeFrame: at hours 0,6,12,24,48,72 post establishment of extracorporal membrane oxygenation (ECMO)
measure: Mortality
timeFrame: 30 days post enrollment
Other outcomes:
Locations:
city: Hamburg
country: Germany
facility: University Hospital Hamburg-Eppendorf
Study officials:
affiliation: Universitätsklinikum Hamburg-Eppendorf
name: Jens Kubitz, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Adrie C, Laurent I, Monchi M, Cariou A, Dhainaou JF, Spaulding C. Postresuscitation disease after cardiac arrest: a sepsis-like syndrome? Curr Opin Crit Care. 2004 Jun;10(3):208-12. doi: 10.1097/01.ccx.0000126090.06275.fe.
citation: Kellum JA, Song M, Venkataraman R. Hemoadsorption removes tumor necrosis factor, interleukin-6, and interleukin-10, reduces nuclear factor-kappaB DNA binding, and improves short-term survival in lethal endotoxemia. Crit Care Med. 2004 Mar;32(3):801-5. doi: 10.1097/01.ccm.0000114997.39857.69.
citation: Peng ZY, Carter MJ, Kellum JA. Effects of hemoadsorption on cytokine removal and short-term survival in septic rats. Crit Care Med. 2008 May;36(5):1573-7. doi: 10.1097/CCM.0b013e318170b9a7.
citation: Tomescu DR, Olimpia Dima S, Ungureanu D, Popescu M, Tulbure D, Popescu I. First report of cytokine removal using CytoSorb(R) in severe noninfectious inflammatory syndrome after liver transplantation. Int J Artif Organs. 2016 May 16;39(3):136-40. doi: 10.5301/ijao.5000489. Epub 2016 Apr 14.
citation: Bruenger F, Kizner L, Weile J, Morshuis M, Gummert JF. First successful combination of ECMO with cytokine removal therapy in cardiogenic septic shock: a case report. Int J Artif Organs. 2015 Feb;38(2):113-6. doi: 10.5301/ijao.5000382. Epub 2015 Feb 3.
citation: Bernardi MH, Rinoesl H, Dragosits K, Ristl R, Hoffelner F, Opfermann P, Lamm C, Preissing F, Wiedemann D, Hiesmayr MJ, Spittler A. Effect of hemoadsorption during cardiopulmonary bypass surgery - a blinded, randomized, controlled pilot study using a novel adsorbent. Crit Care. 2016 Apr 9;20:96. doi: 10.1186/s13054-016-1270-0.