Randomized Controlled Trial of Impregnated Central Venous Catheters for Reducing Bloodstream
Infection in Children (Catch Trial) by Quen Mok.
Hi. My name is Quen Mok.
I'm a consultant intensivist at Great Ormond Street Hospital in London.
I would like to share with you the results of our Catch Trial.
As you know, the blood stream infection rate is the highest in the PICU.
And 70% of these are due to catheter related infections.
And the Catch Trial is looking at a randomized controlled trial of impregnated central venous
catheters for reducing blood stream infection in children.
This trial was funded by the National Institute of Health Research.
And the ethics approval was from the Southwest England Research Ethics Committee.
We have no other conflicts of interest to declare.
The Catch Trial was a randomized controlled trial of children who would be admitted to
the intensive care unit who were aged under 16. The patients had to require a central venous
catheter for at least three days.
We compared heparin or antibiotic catheters with standard catheters.
And we looked at hospital-acquired blood stream infection as the primary outcome.
All these catheters are already in use in the UK, though the most widely used catheter
is the standard catheter.
The UK Saving Lives Initiative, trying to look at the reduction in health care associated
infection, recommended that standard central venous catheters should be used for all patients.
And you should only consider antibiotic impregnated catheters if the catheter was meant to be
in for a longer duration, or that the patient had a higher risk of catheter related blood
stream infection.
However, there were no specific-- child specific guidelines.
And when we did a survey of the PICUs in UK before we started the trial, we noticed that
most of them were using standard catheters, although there were some units that were using
heparin or antibiotic catheters.
We compared two groups of patients that were going to be admitted to the PICU.
The patients who are going to be admitted after elective surgery would be consented
before they were randomized to the central venous catheter.
For the emergency group of patients, because they needed the catheter as part of their
resuscitation, the line was inserted first.
And ideally, the parents will then consent it within 48 hours of insertion of the line.
The primary outcome was blood stream infection from 48 hours after insertion of the catheter
to 48 hours after removal of the catheter.
1,200 Patients were required to achieve an 80% power to detect a relative risk reduction
of 0.5 at a 5% level of significance, with a baseline infection rate of, at the time
of the design of the trial, it was at 10%.
We started recruitment in December 2010, and we recruited over two years till November
2012.
Although 1,200 patients were required for 80% power of the study, we were recommended
by the trial steering committee to continue with recruitment, because the infection rate
had reduced by the time the trial started.
And you can see from the slide that we managed to recruit 1,859 patients by the time of trial
closure, of which 1,485 consented to continue with the trial.
The proportion of patients is very similar to our usual case mix, with 1/3 of patients
being elective patients, where prospective consent was obtained, and 2/3 of the patients
were emergency patients who admitted, and deferred consent was obtained from this group
of patients.
You can see from the table that almost equal numbers of patients were recruited to all
three arms of the trial.
There were certain patients who, after randomisation, either did not require a line any longer,
and no line was inserted, or they received in error-- a different line that they were
randomized to, but the study was analyzed to intention to treat.
You can see that there were almost equal numbers of patients that did not consent to continuing
with the trial.
Looking at our baseline characteristics, there's no difference between the groups.
In age, reason for admission, the PIM score, or the place or site of CVC insertion, 57%
of our patients were under a year of age.
As you can see from this table, over 3% of patients in the heparin and standard groups
got a primary blood stream infection compared to 1% of the patients in the antibiotic group.
The infections include a gram positive or gram negative organisms, as well as Candida.
And looking at the hazard ratio of the results, there was no difference, no significant difference,
between the impregnated catheters versus the standard catheters.
But if you did a pairwise analysis, the antibiotic lines led to a 57% reduction in infection
rate compared to the standard lines, and a 58% reduction in infection rate compared to
the heparin bonded lines.
We had a 75% reduction in risk of catheter related bloodstream infections compared to
standard catheters if we used antibiotic central venous catheters.
The absolute risk reduction was to 2.15% of antibiotic compared to standard catheters,
which meant that we had a number needed to treat a 47 to prevent one blood stream infection.
There was no difference in adverse events in the secondary outcome analysis.
And there was no difference in thrombosis or death rates.
By the time we started the trial, there was already a reduction in the bloodstream infection
rate.
There was no trial effect, as there was a 15% reduction rate in the participating Catch
PICUs, as well as in the nonparticipating PICUs.
And by the time the Catch recruitment period started, the rate of infection was already
down to about 5% compared to 10%.
The cost impact study from the trial showed that antibiotic central venous catheters dominated
the standard catheters with a saving of almost 100,000 pounds for each blood stream infection
that was averted.
The cost saving occurred up to 120 days after randomization, but not beyond six months after
randomization.
So we can see that, despite the decline in BSI rates across the PICUs, the cost of purchasing
the antibiotic CVCs, for all children who required them, was still less than the cost
of managing a bloodstream infection, even if the infection rates were as low as 1.2
per 1,000 bed-days.
You can see from this graph that with a big unit like ours, where there were 1,200 patients
a year.
And with the BSI rates of 4.6%, we would have a saving of about 4,000 pounds.
And if the infection rate continued to go down, we would break even at the BSI rate
of 1.2 per 1,000 bed-days if we changed over to completely using all antibiotic central
venous catheters.
Even if you were a small unit with smaller numbers of admissions, there would be cost
saving down to an infection rate as low as 1.2 per 1,000.
Our microbiologists were concerned that we would be generating antibiotic resistance
if we had widespread implementation of antibiotics central venous catheters across, in our PICUs.
The antibiotic catheters were impregnated with minocycline and rifampicin.
We asked for the centers to test all blood stream infections with the Etest strips.
However, this varied between centers, and not all positive blood cultures were tested.
However, when it was tested, resistance was found in all three groups, not just in the
antibiotic CVC group.
Also, we found that the other studies and surveillance in adults who have been using
these antibiotic CVCs for a lot longer have shown that their risk are very small.
So we are not concerned about antibiotic resistance, but we recommend surveillance once this has
been introduced.
So in conclusion, antibiotic CVCs were associated with a low rate of blood stream infection
when compared to standard and heparin-bonded lines.
They are cost effective from savings associated with a blood stream infection averted, even
for a low BSI rate.
We are also very proud of the Catch achievements from this study.
We were the first study to use deferred consent in children.
We were also the first study to demonstrate that co-entrollment into more than one study
did not affect study recruitment.
We were also the first study to use data linkage of routinely collected patient data to show
generalizability of the study to the PICU population.
You can see from this slide that, of the almost 1,300 patients that were randomized in the
emergency group, and in the ones that we had an opportunity to approach, 984, or 76%, of
the patients consented to being enrolled in the study, and for the use of the data.
24% did not consent.
And you can see that there's a bigger proportion of patients who died in the PICU in the non-consent
group.
The failure to obtain consent was mainly due to lack of opportunity to consent the parents,
either because they were discharged early or transferred to another PICU.
The difficulties in seeking consent for children who died was the main reason expressed by
the research nurses of why they did not feel they could approach the parents of children
who had died in the PICU.
There were a high proportion of death, therefore, in the non-consented patients, and obviously
we risk missing an important group of patients.
However, we could see from the deferred consent study that the consent rate was not affected
by deferred consent.
69% of patients in the elective group consented compared to 84% of patients in the emergency
group.
Also, looking at co-enrolling more patients into more than one study, in our unit, we
were already participating in the control hypoglycemia in pediatric trial, which was
nearing the end of recruitment.
We were co-enrolling these patients into both studies, but we approached the patients in
the CHiP study first so that we did not jeopardize their recruitment.
You can see from the patients who consented to CHiP, the majority of them also consented
to the Catch trial.
But of the patients who did not consent to CHiP trial, many of them also consented to
the Catch trial.
So you can see that the consent rate for CHiP was not affected at all by co-enrollment,
and even the consent rates for Catch.
The patients who were coenrolled into more than one study had a consent rate that was
very similar to the overall population.
So for most parents, it was acceptable to consent to more than one trial, as long as
the trial was safe, and the intervention was already routinely used in the PICU.
It was important that the research nurses coordinated their consent with the patients,
and there was an appropriate time when you should approach the parents to obtain optimum
consent rate.
In conclusion, we would like to acknowledge all the research teams and the clinical trials
unit in the Catch study.
We particularly want to thank the principal investigators, and the research nurses in
the 14 PICUs, and especially, we want to thank all the parents of the children who participated
in the trial.
I hope you found the results of the Catch Trial interesting, and you have learned something
from this, and maybe might introduce using antibiotic lines in your PICU.
And hopefully, this will lead to a reduction in the infection rate.
Thank you for watching the video.
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