Category Archives: Clinical Trials

The PARTNER trial

The PARTNER trial was presented today (published over the summer in NEJM) which is the latest in the critical care community’s attempt to support families with loved ones in ICU.

We know that its a stressful time for families (and of course patients) and we think we could do better in communication with them, and support.

The family members who are involved in the discussion around care and end of life and limitation of treatment often suffer psychological morbidity

Could these outcomes for families be improved by “reengineering” the ICU team and up-skilling them? And interestingly, might that even extend to less burden of treatment for patients?

Thats what the partner trial set out to discover and Derek Angus presented the results this morning in Paris

At its heart PARTNER was a nurse driven emotional support and relationship building intervention

The key thrust of the intervention was around 3 things

  1. Protocolled pathway of family support
  2. Advanced communication skills training for staff
  3. Intensive implementation support of the pathway

It was a stepped wedge cluster RCT in 5 different ICUs  of differing sizes and case mix.

It didn’t show a difference in its primary outcome (HADS score) but it did improve how people felt – families AND nurses! Which is promising – but the real win was reduced length of stay for me, a relatively cheap intervention that saves money, sounds good huh!

Of note there was an apparent increase in ICU mortality, as some patients had treatment limited earlier – but that disappeared at later follow up.

If you are interested in the field its worth reading this study from Curtis et al which was similar but did show a difference in depressive symptoms in families later on… Why? not sure – perhaps just the play of chance??? Perhaps difference in the way the intervention was blanket applied?

Your roving reporter, JS

Effect of Systematic Intensive Care Unit Triage on Long-term Mortality Among Critically Ill Elderly Patients in France

Hot Topics Session

It is well recognised that critically ill elderly patient have a higher mortality and therefore the beneficial effect of intensive care unit (ICU) admission variable ICU use among this population have let to significant difference in uptake.

Guidet and colleagues performed a cluster, randomised trial of admission versus standard care in 3036 elderly patients aged 75 years and above. In their multicentre randomised trail, suitable patients were allocated to routine or non-routine admission as per the following:

CONSORT Diagram

Outcome Measures

  • Primarily 6 months
  • Secondarily ICU admission rate, in-hospital death, functional status and quality of life.

 

Results

Results

 

  • Disappointingly there was no difference seen in any of the outcome measures, even after adjustment for differences in illness severity and patients admitted to ICU had an INCREASED risk of death at six months despite an increase ICU admission rates.
  • Functional status and physical quality of life at six months did not differ significantly.

 

What does this mean?

  • As our ICU population changes it may be that a systematic approach which admits all elderly patients has no effect upon outcome.
  • Further international trials are needed before we know whether this is applicable to other populations.

Clinical Trials in Intensive Care (Tuesday)

TRISS follow up

Long-term outcomes in patients with septic shock transfused at a lower versus a higher haemoglobin threshold: The TRISS randomised, multicentre, clinical trial presented by Sofie Louise Rygaard, Copenhagen, Denmark (Great – she has joined twitter! )

Great stuff from the TRISS trial – which has already told us that a lower haemoglobin target is safe in septic shock and anaemia.  In this follow up long term outcomes of mortality and health related quality of life at 1 year where not significantly different in the intervention group.

As Professor Angus commented after the presentation – this critical care trial that planned long term follow up from the beginning and has now done long term follow up is to be applauded.  It seems safe to continue with a restrictive transfusion policy.

Expecting transfusion to affect mortality 2 years later may have been a bit of a stretch:

… but I think the trial is important. The paper was published in ICM – available here

GRAVITY VAP

Lateral-trendelenburg position to avoid ventilator-associated pneumonia presented by Gianluigi Li Bassi, Barcelona, Spain.

Ive been waiting for this trial for a while because it is interesting – it was challenging a dogma – (putting the bed/patient head up reduces pneumonia) for which the evidence is pretty weak, but has made it into many bundles and guidelines.

It didn’t really work sadly, the study was stopped after 400 patients as there were several adverse events in the group put head down (lateral) and there was too a low an incidence of VAP:

I don’t think its published yet.  The trial used Facebook and Twitter to help communicate as many now do.

CLASSIC trial

Restricting volumes of resuscitation fluid in patients with septic shock: The CLASSIC randomised, parallel-group, multicentre feasibility trial presented by Peter Buhl Hjortrup, Copenhagen, Denmark (twitter)

Available to read now in Intensive Care Medicine, this trial set itself up for a win, by setting its primary endpoint as actually achieving the intervention.  Not to be flippant this is harder than it seems, and they did manage it.  A feasibility trial, they have plans for a large scale trial.

The bottom line crew are all over this of course… Thanks Segun for this review.

OPERA
Effect of postoperative high-flow nasal cannula vs conventional oxygen therapy on hypoxemia in patients after major abdominal surgery: A randomised clinical trial presented by Samir Jaber, Montpellier, France

Headline: extubating onto optiflow doesn’t change hypoxaemia and stopping optiflow doesn’t cause rebound hypoxaemia. In this study. Read the paper in JAMA.

RAPIT

Improving quality of life and psychological recovery in post intensive care patients: A pragmatic multicentre randomised controlled trial, the RAPIT study presented by Janet Froulund Jensen, Hillerød, Denmark

Trial can be read in full here.  The intervention was a programme of ICU photographs and 3 follow ups over a year post ICU discharge. It might have caused less anxiety, but overall made no impact on their primary or secondary outcomes.

Also presented where:

The association between tracheal intubation during paediatric in-hospital cardiac arrest and survival
presented by Lars W. Andersen, Aarhus, Denmar

No difference in ROSC or neurological outcome found. Read the paper in JAMA.

and

Neurally Adjusted Ventilatory Assist as an alternative to Pressure Support Ventilation – A multicentre randomised trial presented by Alexandre Demoule, Paris, France

Patients felt less breathless with NAVA, but otherwise study summed up well in this tweet:

Clinical Trials in Intensive Care (Monday)

INSTINCT

Intravenous polyspecific immunoglobulin G for patients with necrotizing soft tissue infection: Results of the randomised, blinded, placebo-controlled INSTINCT trial – presentation by Martin Bruun Madsen, Copenhagen, Denmark

This trial looked at all comers with necrotising soft tissue infections and was a blinded RCT using IV IG versus placebo.  They found no difference. Does this mean we should stop giving what is an expensive treatment with no benefit to people with necrotising fascitis? Not sure yet…

Read the paper when you can…

SPICE-PAD

Early pain, agitation, depth of sedation and mobilisation as predictors of 180-day mortality: A multinational prospective longitudinal cohort study (The SPICE-PAD Study).

Speaker: Yahya Shehabi, Sydney, Australia

Interesting observational study that shows that these things do predict mortality.  But this is an association – is more work needed progress this?  It uses the “sedation index”  taking the mean of the sedation part of the RASS scores for a day.

IRONMAN

Intravenous iron or placebo for anaemia in intensive care: The IRONMAN randomised controlled trial

This trial IS available to read here.  Also its PI Ed Litton is on twitter and seems very amenable to interaction! Overall It didn’t show a benefit of infusing Iron.  Enteral iron doesn’t work in ICU pts as hepcidin (the “master regulator”) is generally raised as an acute inflammatory marker and prevents absorption, but previous reports of reaction to Iron infusions have put people off using it – IRONMAN showed it is safe in ICU patients.  But its not an effective way to reduce transfusion, although it may have suffered from being underpowered.

Nitric oxide administration during paediatric cardiopulmonary bypass: A randomised controlled trial

Speaker: Warwick Butt, Melbourne, Australia

 

This trial (also published in ICM) looked giving Nitric Oxide to children on bypass – previous data has been encouraging. The rationale is that bypass causes SIRS (from contact activation, ischaemia reperfusion, direct myocardial injury & transfusion) and that NO may help prevent this  – it decreases infarct size in ischaemia reperfusion in rats for example, and recent adult trials have been positive.

The trial found a significant difference and low cardiac output syndrome was halved in group given nitric oxide

HYPRESS

Hydrocortisone for Prevention of Septic Shock (HYPRESS): A randomised controlled trial

Headline from this trial was that Steroids don’t prevent septic shock.  The trial was contemporaneously published in JAMA.

Some good comments after the presentation from Todd Dorman (SCCM president) – The study was probably underpowered (as septic shock was only present in 20% of patients), the finding that in the group who received steroids there was less delirium is “interesting” and recruitment was prolonged – 5 years a long time in ICM and background care probably changed a fair amount over that time.

 

DESIRE

Dexmedetomidine for ventilated septic patients in ICU: A multicentre randomised controlled trial

Speaker: Kyohei Miyamoto, Wakayama, Japan

Interesting study that tried to test the idea that dexmetotomidine is immunonodulatory and therefore useful in sepsis (as a sedation agent).  It made no difference to the outcome (ventilator free days or mortality) but:

 

A fair comment was made that as an open label trial, it carried a high risk of bias which makes the “quality of sedation”  finding more difficult to interpret.

Last but not least…

MACMAN

(McGrath Mac videolaryngoscope versus Macintosh laryngoscope for orotracheal intubation in intensive care patients: The randomised multicentre MACMAN trial)

This neat trial from Jean-Baptiste Lascarrou (available on twitter) looked at a video laryngoscope called McGrath and tried to see if it could increase first pass intubation rates from 65% to 80% compared with direct laryngoscopy with a macintosh blade. In the end it didn’t and both groups had a 70% first pass rate.  The interesting thing was, as you might expect if you regularly use these devices, that the reason for failure was different – In some ways it is a compromise between getting a good view (harder with mac) and getting the tube in (harder with a video laryngoscope in this case McGrath)