PROF. JAN WERNERMAN'S WIDER PERSPECTIVES - TARGET TRIAL

Video Interview with Professor Jan Wernerman of Intensive Care Medicine, Karolinska Institutet, Stockholm, Sweden by Meg Blogg Marquardt, Nestlé Health Science.

From ESICM Paris 23^rd October 2018

MB: … the TARGET trial that was presented yesterday: there has been some discourse around the anticipation of this study being presented.  What are your thoughts?

JW: Yes, I mean to start with, which was emphasised by the presenting author yesterday, is that it’s a large trial and it is…it’s blinded.  I mean the enteral nutrition given to the patients, two different compounds, was blinded to everybody, basically. And it could perhaps be deduced by nurses in terms of more hyperglycaemia but not obviously. So that is the first thing that makes it special. It’s a large trial.  And then you can discuss whether the question is good enough for all the works that has been put into the study.  I mean what is given is that they have two compounds, two formulas that were equal in protein but different in caloric intake. So one formula 1.5 Kcal/ml and the other 1.0, resulting in mean caloric intake of 1,200 and 1,800 respectively. So…and they had a primary endpoint of 90-day mortality and there was no difference in that.  There was no difference in pre-defined subgroups but the subgroups were very conventionally defined.  So I’m not so sure that that is the end of the story.  The investigation has which was not obviously from the publication, a lot of accessory studies looking at other endpoints and so on perhaps in subgroups of patients and this may contain important information which will be hypothesis generating. But in general terms, if you have asked me before I knew the results I would have predicted the results. I would have been very astonished if there was a difference to be in this.  So that’s why I say there was all this manpower, womanpower used in the study, a good investment. It’s…the Australians are to be congratulated, I shouldn’t be too negative, and every study, particularly a high-quality study in many respects, but also they disregarded indirect calorimetry because they think that it’s not standard in university unit and I disagree to that.  I think that the protocol in that sense would have been…it would have been a good thing to adjust it to energy expenditure, like they did in the EAT-ICU study. So I don’t know why…I’m not sure I agree to that the study result is controversial. I mean it deserves attention, no doubt, but…

MB: Because of the size and the way it is being done…

JW: Yeah, so the size and some parts of the quality, but it’s done at the same time I think that we should advance beyond that. But, okay, the study was designed a long time ago and this is always the issue. So…

MB: Is it likely to make a change to clinical practice?

JW: No, probably not. I mean it confirms what we have seen beforehand and still, I mean, these patients, I don’t recall exactly if it was 4,000 patients, something like that, and I mean they were selected out of 40,000 or something like that patients. So I mean this is a subgroup of patients that fitted in, that were given enteral nutrition, that was supposed to being mechanically ventilated for a certain period of time and so on but it’s an important core group of patients but just to fit into guidelines, I think it won’t change practice. I can’t see how it will do that.

MB: Are there any takeaways from the results of this study?

JW: I mean that is the limitation. I mean…we…it confirms our present opinion, prejudice, call it what you want. I mean it’s only partly evidenced based but to give… I mean you can anticipate that they used ideal bodyweight as the reference, so it was 19 Kcal/kg ideal bodyweight in the low group and 29, something like that, in the other group. And I can’t see that we do differently or give recommendation differently. What you can say here is that they didn’t have any problems to… if you look upon the intake, I think they reached it, they were selected because they could accept enteral nutrition and that excludes a number of patients but there is a problem to initiate, perhaps not initiate but at least to advance enteral nutrition and these are not covered by the inclusions in the study. No, I’m sorry, but I mean once upon a time when the EPaNIC was presented, for me personally, it meant that the next day we changed practice for the information in the initial publication. And, okay, I have just one day to read the manuscript but I can’t see this. 

MB: Okay. Thank you very much for your commentary. It’s been a pleasure. 

END.