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Sections: Correlations,
Clinical Trials, and HPO
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| drug4390 | behavioral lifestyle intervention Wiki | 1.00 |
| Name (Synonyms) | Correlation |
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Navigate: Correlations HPO
There is one clinical trial.
The COVID-19 pandemic has led to shortages of intravenous sedatives due to increased ICU patient admissions and greater use of mechanical ventilation. A shortage of sedatives is as concerning as a shortage of mechanical ventilators since critically ill patients require sedation for comfort and to tolerate mechanical ventilation. Anti-adrenergic medications are increasingly recognized for their role in sedation of critically ill patients. Propranolol is a plentiful and inexpensive, non-selective beta-adrenergic blocker with good penetration of the blood-brain barrier, which can reduce agitation and arousal. The study team published a single-centre retrospective study of 64 mechanically-ventilated patients which found the initiation of propranolol was associated with an 86% reduction in propofol dose and a roughly 50% reduction in midazolam dose while maintaining the same level of sedation. Propranolol has the potential to mitigate the threat posed by worldwide sedative shortages and improve critical care management of patients who require mechanical ventilation. This study seeks to evaluate whether the addition of propranolol to a standard sedation regimen reduces the dose of sedative needed in critically ill patients requiring mechanical ventilation. This study is an open-label randomized controlled trial, single-blinded with 1:1 allocation. Both arms will receive sedation according to usual intensive care unit practice with a sedative agent. The intervention arm will additionally receive enteral propranolol 20-60mg q6h titrated up over 24-48h until intravenous sedative doses have fallen to a minimal level (propofol <0.5mg/kg/h or midazolam <0.5mg/h) or the maximum dose of propranolol is reached. Intravenous sedative doses will be titrated downwards in response to sympatholysis produced by the propranolol, as evidenced by a decreasing heart rate or blood pressure. The control arm will receive sedation without the addition or propranolol. The primary outcome will be the change in primary sedative dose from baseline to Day 3 of enrollment. Analysis of the primary outcome will be a difference in differences; the change in sedative dose from baseline to Day 3 in the intervention group versus the same change in the control group. The Mann-Whitney U test will be used as a nonparametric test of independent samples for this outcome.
Description: Change from baseline in total daily dose of primary sedative on Day 3
Measure: Primary sedative dose change Time: 24 hours prior to enrollment to Day 3 of the study (60-84hrs after enrollment)Description: Proportion of measured sedation scores within target range (to be defined a priori by treating team): Richmond Agitation-Sedation Scale and/or the Sedation-Agitation Scale
Measure: Sedation scores Time: Daily upon enrollment until study completion (discharge from ICU, 28 days, or death - whichever is first)Description: Proportion of participants whose sedative dose on day 3 are below a minimum level (propofol <0.5mg/kg/h or midazolam <1.9mg/h)
Measure: Primary sedative dose Time: Day 3 of study (60-84hrs after enrollment)Description: Change from baseline in total daily dose of all sedatives (in mg of midazolam equivalents) on Day 3
Measure: Total sedative daily dose change Time: 24 hours prior to enrollment to Day 3 of the study (60-84hrs after enrollment)Description: Change from baseline in total daily dose of all opioids (in mcg of fentanyl equivalents) on Day 3
Measure: Total opioid daily dose change Time: 24 hours prior to enrollment to Day 3 of the study (60-84hrs after enrollment)Description: Incidence of bradycardia (HR <50 or requiring intervention)
Measure: Adverse event - bradycardia Time: Daily from study enrollment until study completion (discharge from ICU, 28 days, or death - whichever is first)Description: Incidence of hypotension (MAP <60 requiring new vasopressor agents or an increase of >0.1 mcg/kg/min of norepinephrine or epinephrine persisting more than 2h after reducing sedative doses)
Measure: Adverse event - hypotension Time: Daily from study enrollment until study completion (discharge from ICU, 28 days, or death - whichever is first)Description: Incidence of clinically-important bronchospasm requiring a change in mechanical ventilation settings
Measure: Adverse event - bronchospasm Time: Daily from study enrollment until study completion (discharge from ICU, 28 days, or death - whichever is first)Description: Incidence of new ECG conduction delays
Measure: Adverse event - ECG conduction delays Time: Daily from study enrollment until study completion (discharge from ICU, 28 days, or death - whichever is first)Description: Total number of days of propranolol use
Measure: Duration of propranolol use Time: Daily from enrollment to study withdrawal/completion (last day of propranolol dose given; discharge from ICU, 28 days, or death - whichever is first)Description: Mean propranolol dose on day 3
Measure: Propranolol dose Time: Day 3 of study (60-84hrs after enrollment)Description: Mean number of ventilator-free days in first 30 days of hospital intensive care unit admission
Measure: Ventilator-free days Time: Day 1 of admission to the intensive care unit until 30 days, discharge from intensive care, or death (whichever is first)Description: Mean number of delirium-free days in first 30 days of hospital intensive care unit admission, measured using the Intensive Care Delirium Screening Checklist
Measure: Delirium-free days Time: Day 1 of admission to the intensive care unit until 30 days, discharge from intensive care, or death (whichever is first)Description: Mean length of stay in hospital
Measure: Hospital Length of Stay Time: Day 1 of hospital admission until hospital discharge date or date of death (whichever is first)Description: Mean length of stay in the intensive care unit
Measure: Intensive Care Unit Length of Stay Time: Day 1 of intensive care unit admission until discharge date from intensive care unit or date of death (whichever is first)Description: Mortality rate among participants while in hospital
Measure: Hospital Mortality Time: Upon study completion (after all 108 participants have completed the study, estimated at 6 months) and after 50 patients have been enrolled (estimated at 3 months)Description: Mean cost of sedative medication used in the intensive care unit among the intervention and control arms
Measure: Direct Costs Time: Upon study completion (after all 108 participants have completed the study, estimated at 6 months)Alphabetical listing of all HPO terms. Navigate: Correlations Clinical Trials
Data processed on September 26, 2020.
An HTML report was created for each of the unique drugs, MeSH, and HPO terms associated with COVID-19 clinical trials. Each report contains a list of either the drug, the MeSH terms, or the HPO terms. All of the terms in a category are displayed on the left-hand side of the report to enable easy navigation, and the reports contain a list of correlated drugs, MeSH, and HPO terms. Further, all reports contain the details of the clinical trials in which the term is referenced. Every clinical trial report shows the mapped HPO and MeSH terms, which are also hyperlinked. Related HPO terms, with their associated genes, protein mutations, and SNPs are also referenced in the report.
Drug Reports MeSH Reports HPO Reports