Study protocol and statistical analysis plan for the Liberal Glucose Control in Critically Ill Patients with Pre-existing Type 2 Diabetes (LUCID) trial

2020 ◽  
Vol 22 (2) ◽  
pp. 133-141
Author(s):  
Alexis P Poole ◽  
◽  
Mark E Finnis ◽  
James Anstey ◽  
Rinaldo Bellomo ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Clinical Trial ◽  
Clinical Trials ◽  
Intensive Care ◽  
Blood Glucose ◽  
Statistical Analysis ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Statistical Analysis Plan

BACKGROUND: Contemporary glucose management of intensive care unit (ICU) patients with type 2 diabetes is based on trial data derived predominantly from patients without type 2 diabetes. This is despite the recognition that patients with type 2 diabetes may be relatively more tolerant of hyperglycaemia and more susceptible to hypoglycaemia. It is uncertain whether glucose targets should be more liberal in patients with type 2 diabetes. OBJECTIVE: To detail the protocol, analysis and reporting plans for a randomised clinical trial — the Liberal Glucose Control in Critically Ill Patients with Pre-existing Type 2 Diabetes (LUCID) trial — which will evaluate the risks and benefits of targeting a higher blood glucose range in patients with type 2 diabetes. DESIGN, SETTING, PARTICIPANTS AND INTERVENTION: A multicentre, parallel group, open label phase 2B randomised controlled clinical trial of 450 critically ill patients with type 2 diabetes. Patients will be randomised 1:1 to liberal blood glucose (target 10.0–14.0 mmol/L) or usual care (target 6.0–10.0 mmol/L). MAIN OUTCOME MEASURES: The primary endpoint is incident hypoglycaemia (< 4.0 mmol/L) during the study intervention. Secondary endpoints include biochemical and feasibility outcomes. RESULTS AND CONCLUSION: The study protocol and statistical analysis plan described will delineate conduct and analysis of the trial, such that analytical and reporting bias are minimised. TRIAL REGISTRATION: This trial has been registered on the Australian New Zealand Clinical Trials Registry (ACTRN No. 12616001135404) and has been endorsed by the Australian and New Zealand Intensive Care Society Clinical Trials Group.

Statistical analysis plan for evaluating different intensities of blood pressure control in the ENhanced Control of Hypertension And Thrombolysis strokE stuDy

2018 ◽  
Vol 14 (5) ◽  
pp. 555-558 ◽  
Author(s):  
Craig S Anderson ◽  
Mark Woodward ◽  
Hisatomi Arima ◽  
Xiaoying Chen ◽  
Richard I Lindley ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Clinical Trial ◽  
Clinical Trials ◽  
Body Weight ◽  
Statistical Analysis ◽  
Lower Risk ◽  
Standard Dose ◽  
Statistical Analysis Plan ◽  
Symptomatic Intracerebral Hemorrhage ◽  
Stroke Study

Background The ENhanced Control of Hypertension And Thrombolysis strokE study (ENCHANTED) trial was initiated as a 2 × 2 partial-factorial active-comparison, prospective, randomized, open, blinded endpoint clinical trial to evaluate in thrombolysis-eligible acute ischemic stroke (AIS) patients whether: (1) Arm A – low-dose (0.6 mg/kg body weight) intravenous (iv) alteplase has noninferior efficacy and lower risk of symptomatic intracerebral hemorrhage (sICH) compared with standard-dose (0.9 mg/kg body weight) iv alteplase; and (2) Arm B – early intensive blood pressure (BP) lowering (systolic target 130–140 mmHg) has superior efficacy and lower risk of ICH compared with guideline-recommended BP control (systolic target <180 mmHg). Arm A was completed in 2016; Arm B is now concluding. Objective To outline in detail and make public the predetermined statistical analysis plan (SAP) for the ‘BP control’ arm of this study. Methods All data collected by participating researchers will be reviewed and formally assessed. Information pertaining to the baseline characteristics of patients, their process of care, and the delivery of treatments will be outlined, and for each item, statistically relevant descriptive elements will be described. For the trial outcomes, the most appropriate statistical comparisons to be made between groups are planned and described. Results A SAP was developed for the results of the BP control arm of this study that is transparent, available to the public, verifiable, and predetermined before completion of data collection. Conclusions We have developed a predetermined SAP for the ENCHANTED BP control arm to be followed to avoid analysis bias arising from prior knowledge of the study findings. Clinical trial registration ClinicalTrials.gov (NCT01422616); ISRCTN Register (ISRCTN82387104); Australian New Zealand Clinical Trial Registry (ACTRN12611000236998); EU Clinical Trials Register (2011-005545-12); and Clinical Trials Registry – India (REF/2017/05/014334).

scholarly journals Evaluating probiotics for the prevention of ventilator-associated pneumonia: a randomised placebo-controlled multicentre trial protocol and statistical analysis plan for PROSPECT

BMJ Open ◽  
2019 ◽  
Vol 9 (6) ◽  
pp. e025228 ◽  
Author(s):  
Jennie Johnstone ◽  
Diane Heels-Ansdell ◽  
Lehana Thabane ◽  
Maureen Meade ◽  
John Marshall ◽  
...  
Keyword(s):  
Statistical Analysis ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Controlled Trial ◽  
Statistical Analysis Plan ◽  
Hospital Length Of Stay ◽  
Sensitivity Analyses ◽  
Ventilator Associated Pneumonia ◽  
Increased Risk ◽  
The Impact

IntroductionVentilator-associated pneumonia (VAP) is the most common healthcare-associated infection in critically ill patients. Prior studies suggest that probiotics may reduce VAP and other infections in critically ill patients; however, most previous randomised trials were small, single centre studies. The Probiotics: Prevention of Severe Pneumonia and Endotracheal Colonization Trial (PROSPECT) aims to determine the impact of the probioticLactobacillus rhamnosusGG on VAP and other clinically important outcomes in critically ill adults.MethodsPROSPECT is a multicentre, concealed, randomised, stratified, blinded, controlled trial in patients ≥18 years old, anticipated to be mechanically ventilated ≥72 hours, in intensive care units (ICUs) in Canada, the USA and Saudi Arabia. Patients receive either 1×1010 colony forming units ofL. rhamnosusGG twice daily or an identical appearing placebo. Those at increased risk of probiotic infection are excluded. The primary outcome is VAP. Secondary outcomes are other ICU-acquired infections includingClostridioides difficileinfection, diarrhoea (including antibiotic-associated diarrhoea), antimicrobial use, ICU and hospital length of stay and mortality. The planned sample size of 2650 patients is based on an estimated 15% VAP rate and will provide 80% power to detect a 25% relative risk reduction.Ethics and disseminationThis protocol and statistical analysis plan outlines the methodology, primary and secondary analyses, sensitivity analyses and subgroup analyses. PROSPECT is approved by Health Canada (#9427-M1133-45C), the research ethics boards of all participating hospitals and Public Health Ontario. Results will be disseminated via academic channels (peer reviewed journal publications, professional healthcare fora including international conferences) and conventional and social media. The results of PROSPECT will inform practice guidelines worldwide.Trialregistration numberNCT02462590; Pre-results.

scholarly journals A Distribution-based Method for Assessing The Differences between Clinical Trial Target Populations and Patient Populations in Electronic Health Records

2014 ◽  
Vol 05 (02) ◽  
pp. 463-479 ◽  
Author(s):  
P. Ryan ◽  
Y. Zhang ◽  
F. Liu ◽  
J. Gao ◽  
J.T. Bigger ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Clinical Trial ◽  
Clinical Trials ◽  
Electronic Health Records ◽  
Real World ◽  
World Population ◽  
Health Records ◽  
Target Populations ◽  
Electronic Health

SummaryObjective: To improve the transparency of clinical trial generalizability and to illustrate the method using Type 2 diabetes as an example.Methods: Our data included 1,761 diabetes clinical trials and the electronic health records (EHR) of 26,120 patients with Type 2 diabetes who visited Columbia University Medical Center of New-York Presbyterian Hospital. The two populations were compared using the Generalizability Index for Study Traits (GIST) on the earliest diagnosis age and the mean hemoglobin A1c (HbA1c) values.Results: Greater than 70% of Type 2 diabetes studies allow patients with HbA1c measures between 7 and 10.5, but less than 40% of studies allow HbA1c<7 and fewer than 45% of studies allow HbA1c>10.5. In the real-world population, only 38% of patients had HbA1c between 7 and 10.5, with 12% having values above the range and 52% having HbA1c<7. The GIST for HbA1c was 0.51. Most studies adopted broad age value ranges, with the most common restrictions excluding patients >80 or <18 years. Most of the real-world population fell within this range, but 2% of patients were <18 at time of first diagnosis and 8% were >80. The GIST for age was 0.75. Conclusions: We contribute a scalable method to profile and compare aggregated clinical trial target populations with EHR patient populations. We demonstrate that Type 2 diabetes studies are more generalizable with regard to age than they are with regard to HbA1c. We found that the generalizability of age increased from Phase 1 to Phase 3 while the generalizability of HbA1c decreased during those same phases. This method can generalize to other medical conditions and other continuous or binary variables. We envision the potential use of EHR data for examining the generaliz-ability of clinical trials and for defining population-representative clinical trial eligibility criteria.Citation: Weng C, Li Y, Ryan P, Zhang Y, Liu F, Gao J, Bigger JT, Hripcsak G. A distribution-based method for assessing the differences between clinical trial target populations and patient populations in electronic health records. Appl Clin Inf 2014; 5: 463–479 http://dx.doi.org/10.4338/ACI-2013-12-RA-0105

scholarly journals The effect of insulin administration on c-peptide in critically ill patients with type 2 diabetes

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Marco Crisman ◽  
Luca Lucchetta ◽  
Nora Luethi ◽  
Luca Cioccari ◽  
Que Lam ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Insulin Administration ◽  
C Peptide

scholarly journals Insulin therapy for hyperglycemia in critically ill patients

2016 ◽  
Vol 53 (5) ◽  
pp. 250
Author(s):  
Julianti Julianti ◽  
Silvia Triratna ◽  
Aditiawati Aditiawati ◽  
Irfanuddin Irfanuddin
Keyword(s):  
Intensive Care Unit ◽  
Intensive Care ◽  
Blood Glucose ◽  
Mortality Rate ◽  
Insulin Therapy ◽  
Critically Ill ◽  
Organ Dysfunction ◽  
Critically Ill Patients ◽  
Therapy Group ◽  
Control Group

Background Hyperglycemia in critically ill patients is associated with higher mortality. Insulin therapy may improve outcomes, not only by preventing deleterious effects of hyperglycemia, but by improving the molecular dynamics in organ dysfunction.Objectives To assess the effects of insulin therapy on critically ill patients in an intensive care unit (ICU) setting and the risk of hypoglycemia.Methods An open-label, clinical trial was conducted in the Pediatric Intensive Care Unit (PICU) of Dr. Moh. Hoesin Hospital, Palembang, from November 2011 to March 2012. Subjects were consecutively assigned to receive either regular insulin at a dose of 0.05 U/kg/h if the blood glucose level reached >200 mg%, or standard therapy (control group). Blood glucose levels were measured hourly until they reached 80-110 mg%. Dose adjustments were made when the blood glucose level reached 145 mg%, by reducing the insulin dose to 0.025 U/kg/h. Outcomes of therapy were measured by Pediatric Logistic Organ Dysfunction (PELOD) score improvement, mortality rate and the occurrence of hypoglycemia.Results Forty subjects were enrolled in this study, with 20 subjects assigned to the insulin therapy group and 20 subjects to the standard therapy group. Two subjects, one from each group, were not included in the final analysis due to their deaths within 24 hours. There was no significant difference in distribution of PELOD scores before intervention between the groups (OR=0.5; 95%CI 0.1 to 1.9, P=0.32). However, after intervention, the PELOD scores was significantly lower in insulin therapy group compared to control group (OR 0.2; 95% CI 0.05 to 0.8, P=0.02). In the insulin group after intervention, fewer subjects had scores >20.5 and more subjects had scores ≤20.5, indicated a lower risk of organ dysfunction. There was also a significantly lower mortality rate in the insulin group compared to the control group (OR 0.2; 95% CI 0.05 to 0.8, P=0.02). None of the subjects suffered hypoglycemia.Conclusion Insulin is beneficial in improving organ dysfunction and decreasing mortality for critically ill patients.

scholarly journals Diabetes mellitus is a risk factor for prolonged SARS-CoV-2 viral shedding in lower respiratory tract samples of critically ill patients

Endocrine ◽  
2020 ◽  
Vol 70 (3) ◽  
pp. 454-460 ◽  
Author(s):  
Niccolò Buetti ◽  
Pierpaolo Trimboli ◽  
Timothy Mazzuchelli ◽  
Elia Lo Priore ◽  
Carlo Balmelli ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Cox Model ◽  
Viral Rna ◽  
Rt Pcr ◽  
Viral Shedding

Abstract Purpose The length of time a critically ill coronavirus disease 2019 (COVID-19) patient remains infectious and should therefore be isolated remains unknown. This prospective study was undertaken in critically ill patients to evaluate the reliability of single negative real-time polymerase chain reaction (RT-PCR) in lower tracheal aspirates (LTA) in predicting a second negative test and to analyze clinical factors potentially influencing the viral shedding. Methods From April 9, 2020 onwards, intubated COVID-19 patients treated in the intensive care unit were systematically evaluated for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by RT-PCR of nasopharyngeal swabs and LTA. The time to negativity was defined as the time between the onset of symptoms and the viral clearance in LTA. In order to identify risk factors for prolonged viral shedding, we used univariate and multivariate Cox proportional hazards models. Results Forty-eight intubated SARS-CoV-2 patients were enrolled. Overall, we observed that the association of the first negative RT-PCR with a second negative result was 96.7%. Median viral shedding was 25 (IQR: 21.5–28) days since symptoms’ onset. In the univariate Cox model analysis, type 2 diabetes mellitus was associated with a prolonged viral RNA shedding (hazard ratio [HR]: 0.41, 95% CI: 0.06–3.11, p = 0.04). In the multivariate Cox model analysis, type 2 diabetes was associated with a prolonged viral RNA shedding (HR: 0.31, 95% CI: 0.11–0.89, p = 0.029). Conclusion Intubated patients with type 2 diabetes mellitus may have prolonged SARS-CoV-2 shedding. In critically ill COVID-19 patients, one negative LTA should be sufficient to assess and exclude infectivity.

Effects of Different Blood Glucose Levels on Critically Ill Patients in an Intensive Care Unit

2015 ◽  
Vol 25 (6) ◽  
pp. 388-393 ◽  
Author(s):  
Li Kang ◽  
Juan Han ◽  
Qun-Cao Yang ◽  
Hui-Lin Huang ◽  
Nan Hao
Keyword(s):  
Intensive Care Unit ◽  
Intensive Care ◽  
Blood Glucose ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Fasting Blood Glucose ◽  
Apache Ii Score ◽  
High Blood Glucose ◽  
Glucose Levels ◽  
Blood Glucose Levels

<b><i>Aims:</i></b> We explore the infection incidence and possible prognostic outcome relevance for patients with different blood glucose levels in an intensive care unit (ICU). <b><i>Methods:</i></b> A total of 98 cases were enrolled and divided into three groups based on average fasting blood glucose levels (group A: ≤6.1 mmol/l; group B: 6.1-10 mmol/l; group C: ≥10 mmol/l). <b><i>Results:</i></b> There were no statistical differences in the time to ICU admission, the indwelling durations of gastric tubes, urinary or deep vein catheters, tracheal intubations and tracheotomies, or the length of ventilator use (all p > 0.05). No evident difference in the multiple organ dysfunction syndrome rate was found between the three groups (p = 0.226). The infection and mortality rates between the groups showed significant differences (all p < 0.05). Furthermore, the difference of respiratory system infections was statistically significant among the three groups (p = 0.008), yet no such statistical difference was observed among groups regarding nonrespiratory system infections (p = 0.227). <b><i>Conclusions:</i></b> Critically ill patients with a high blood glucose level were positively correlated with a relatively high APACHE II score and more serious degree of disease, as well as a higher incidence of respiratory infection during their ICU stay than those with lower blood glucose levels (<10 mmol/l).

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