Therapy
 A prospective randomised multi-centre controlled trial on tight glucose control by intensive insulin therapy in adult intensive care units: the Glucontrol study
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Summary
Posted By: Elizabeth Sweetman
E-Mail: easweetm@nsccahs.health.nsw.gov.au
Posted Date: 28/8/09
Title: A prospective randomised multi-centre controlled trial on tight glucose control by intensive insulin therapy in adult intensive care units: the Glucontrol study
Authors: Jean-Charles Preiser
Reference: Intensive Care Med. 2009 Jul 28
Link: Click here for a direct link to the paper. A password may be required for access to fulltext.
Abstract: PURPOSE: An optimal target for glucose control in ICU patients remains unclear. This prospective randomized controlled trial compared the effects on ICU mortality of intensive insulin therapy (IIT) with an intermediate glucose control.
METHODS: Adult patients admitted to the 21 participating medico-surgical ICUs were randomized to group 1 (target BG 7.8-10.0 mmol/L) or to group 2 (target BG 4.4-6.1 mmol/L).
RESULTS: While the required sample size was 1,750 per group, the trial was stopped early due to a high rate of unintended protocol violations. From 1,101 admissions, the outcomes of 542 patients assigned to group 1 and 536 of group 2 were analysed. The groups were well balanced. BG levels averaged in group 1 8.0 mmol/L (IQR 7.1-9.0) (median of all values) and 7.7 mmol/L (IQR 6.7-8.8) (median of morning BG) versus 6.5 mmol/L (IQR 6.0-7.2) and 6.1 mmol/L (IQR 5.5-6.8) for group 2 (p < 0.0001 for both comparisons). The percentage of patients treated with insulin averaged 66.2 and 96.3%, respectively. Proportion of time spent in target BG was similar, averaging 39.5% and 45.1% (median (IQR) 34.3 (18.5-50.0) and 39.3 (26.2-53.6)%) in the groups 1 and 2, respectively. The rate of hypoglycaemia was higher in the group 2 (8.7%) than in group 1 (2.7%, p < 0.0001). ICU mortality was similar in the two groups (15.3 vs. 17.2%).
CONCLUSIONS: In this prematurely stopped and therefore underpowered study, there was a lack of clinical benefit of intensive insulin therapy (target 4.4-6.1 mmol/L), associated with an increased incidence of hypoglycaemia, as compared to a 7.8-10.0 mmol/L target. (ClinicalTrials.gov # NCT00107601, EUDRA-CT Number: 200400391440).
 
Are the Results Valid?
1. Was the assignment of patients to treatments randomized? ( Was allocation concealment maintained?)
Yes patients were randomised to their study groups. Allocation concealment is this trial is unclear ; the authors do not explicitly state the method used to maintain the allocation sequence.
2. Were all patients who entered the trial properly accounted for and attributed at its conclusion?
2a. Was followup complete?
This trial was stopped early following the first interim analysis based on the recommendation of the DSMB. The 1,101 patients randomised during this trial were all accounted for by the authors in the results section of the paper.
(1,101 Patients randomised; 551 patients to BG target 7.8-10.0 mmol/L (group 1) and 550 patients to BG target of 4.4 - 6.1 mmol/L (group 2)
Of the 1,101 patients in the trial however, only 1078 were analysed. 23 of the 1,101 patient’s randomised were stated as re-admissions to the ICU and were not analysed. The authors are not explicit in the reporting of these patients. Outcomes were not reported for these 23 patients.
2b. Were patients analyzed in the groups to which they were randomized?
Unsure. The authors did not explicitly state whether re-admitted patients who had been enrolled into the trial in their previous ICU admission and were analysed in the groups to which they were originally randomized.
3. Were patients, health workers, and study personnel blind to treatment?
The central data manager and the statistician were blinded to treatment assignment.
4. Were the groups similar at the start of the trial?
Yes. The characteristics of patients in each study group were primarily the same. Pre-existing diabetes was slightly higher in group 1 than group 2 and was noted by the authors in the paper.
5. Aside from the experimental intervention, were the groups treated equally?
Patients in both study groups were treated equally. As stated by the authors the only difference between groups, was that Group 2 patients had a higher number vasopressor/inotrope days in the ICU than group 1 (Table 3, 1521 days vs 1350 days, p = <0.0001)
What are the Results?
1. How large was the treatment effect?
PRIMARY OUTCOME:
All cause absolute mortality during ICU stay did not differ between groups.
  • Group 1 – 83/542 (15.3%) vs Group 2 – 92/536 (17.2%) p = 0.410.

    SECONDARY OUTCOMES:
    (No statistically significant differences between groups for any secondary outcomes).

  • 28 Day Mortality - Group 1 – 83/542 (15.3%) vs Group 2 – 100/542 (18.7%) p = 0.1438.
  • Hospital Mortality - Group 1 – 105/542 (19.4%) vs Group 2 – 125/536 (23.3%) p = 0.1136
  • ICU LOS (Days) - Group 1 - 6 Days ; SD 3-13 vs Group 2 – 6 Days ; SD 3-13 p = 0.238.
  • Hospital LOS - Group 1 – 16 Days ; SD 11-29 vs Group 2 – 16 Days ; SD 11-29 p = 0.708.
    • 2. How precise was the estimate of the treatment effect?
    The authors do not report confidence intervals.
    The 95% CI around the primary outcome was calculated. It ranges between 3% benefit to 6.2% harm.
    Will the Results Help Me In Caring For My Patients?
    1. Can the results be applied to my patient care?
    Due to poor compliance in both study arms, it is difficult to interpret the results of this trial. The poor compliance may demonstrate how difficult it is to implement this intervention into normal practice.
    2. Were all clinically important outcomes considered?
    Yes, although mortality at day 90 may have been a better primary outcome than ICU discharge mortality.
    3. Are the likely treatment benefits worth the potential harms and costs?
    Unable to determine from this trial due to early stopping and excessive protocol violations.

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    A prospective randomised multi-centre controlled trial on tight glucose control by intensive insulin therapy in adult intensive care units: the Glucontrol study

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