Hello this is the training module for the use of empiriflozin in the recovery trial this is the current design of the trial which you will be familiar with eligible patients that is those who have suspected or proven kevin 19 who have been admitted to hospital are randomized into one or more arms that are both available at your hospital and suitable for the
Participant not all arms are available in all hospitals or in all countries participants are then followed to collect outcomes at the earliest of death discharge from hospital or 28 days after randomization this training module applies to part f of the main randomization which you can see in the top right of this screen which is between empagliflozin or usual
Care alone this randomization can be done in addition to any of the others which are available at your site hamburglasim is what is known as an sglt2 inhibitor sglt2 the full name of which is sodium glucose co-transporter 2 is the main process by which glucose which has been filtered into the urine by the kidney is then reabsorbed back to the bloodstream sglt2
Inhibitors were developed as treatment for diabetes because they can lower blood sugar by allowing more to escape into the urine however trials of sglt2 inhibitors have shown they have additional benefits beyond simply lowering blood sugar and have been found to reduce the risk of atherosclerotic cardiovascular effects such as myocardial infarction in people with
Type 2 diabetes they also reduce the risk of cardiovascular death in people with heart failure they also slow the progress of chronic kidney disease in people with diabetes and chronic kidney disease there are reasons to think that that sglt2 inhibitors may also be beneficial in calvin 19. they shift energy metabolism from one based on glucose which the sars kv2
Virus may rely on to a lipid-based energy metabolism they also improve endothelial function and have anti-inflammatory effects has been one trial previously done called the dare19 trial which compared dapogloflosing with placebo among 1250 patients hospitalized for covid19 and also had another risk factor for a poor outcome such as diabetes or cardiovascular disease
The primary outcome for the day 19 trial was time to organ failure or death this was numerically reduced albeit not significantly among the people allocated to receive dapagliflozin the recovery trial is therefore testing a drug called empagliflozin another sglt2 inhibitor which we hope will be available in all countries participating in recovery as i said at the
Start this will be a separate factorial randomization to the others and so can be given in addition to other study treatment allocations the dose that we are using in recovery is a standard dose of 10 milligrams once daily for up to 28 days or if the participant is discharged before 28 days then the study treatment is stopped at hospital discharge not everybody
Is suitable for this comparison the main exclusions include people with type 1 diabetes mellitus or post pancreatectomy diabetes mellitus if a patient is normally only on insulin therapy as their diabetes treatment please consider carefully whether the diabetes is type 1 and seek advice if necessary due to the small risk of ketoacidosis in diabetic patients with
This treatment you should also exclude patients with a history of ketoacidosis and other diabetic patients with the current blood ketones of greater than or equal to 1.5 millimoles per liter or urine ketones greater than or equal to two plus on a standard urine dipstick urine testing is recommended when blood ketone testing is not available participants who are
Pregnant or breastfeeding should also be excluded from this comparison of note there are no exclusions around kidney or liver function sglt2 inhibitors do have some adverse effects by far the most commonest of these are what are called mycotic genital infections such as volvo vaginal cardiacism or candida balanitis these are most common in patients with diabetes
They are easily treated with a topical antifungal such as chloramazole cream and usually the study treatment would not need to be stopped sglt2 inhibitors lower blood sugar but by themselves do not cause hypoglycemia but if given in combination with insulin or drugs that stimulate the secretion of insulin such as sulfonyl urea such as glycoside then hypoglycemia
Can occur and it may be necessary to adjust the doses of these other medications while the patient is taking epiglyphalosin sglt2 inhibitors also cause loss of sodium and water through the urine naturesis and osmotic diuresis which can cause volume depletion in some patients so care is required with fluid balance as it is with all patients with kevin 19. a much
Rarer but more severe side effect is ketoacidosis this is defined as a combination of both ketosis and metabolic acidosis as defined by the ketone and bicarbonate parameters shown here this is most common in patients with type 1 diabetes which is why they are excluded from this comparison but it does still occur in patients with type 2 diabetes albeit rare it is
Important to recognize that ketoacidasis in patients taking sglt2 inhibitors can present differently with a relatively normal rather than very high blood sugar this is termed euglycemic ketoacidases therefore as an additional safety measure participants with diabetes who have been allocated empagliflozin should have regular checks of ketones this should be done
Twice daily with blood ketones where possible or once daily using urine ketones if blood ketone testing is not available because of the possibility of euglycemic ketoacidosis ketene should also be checked if there is any clinical concern if ketosis develops that is blood ketones are greater than or equal to 1.5 millimoles per liter or urine ketones are greater
Than or equal to 2 plus teams should ensure patient is receiving adequate fluid calorific intake refer to the local diabetes team if available and follow local protocols for the management of ketosis consider increasing the insulin the participant is on it and consider withholding embryoplethylosin while the participant is ketotic results of ketone testing are
Not required to be stored from the study and samples should be disposed of as per routine clinical practice in order to assess the efficacy and safety of hemoglosis properly in recovery there are some additional outcomes which will be collected on the 28-day follow-up form these include whether the patient experienced ketoacidosis or not that is both ketosis
And metabolic acidosis whether they had severe hypoglycemia and by that we we don’t mean simply an incidental low blood sugar but instead low blood sugar which causes a low consciousness level that requires the help of another person to recover we will also collect whether they had other hyperglycemia by high blood sugar levels that required either the use of
New insulin or were associated with a hyper osmolar state previously known as hyperosmolar non-ketotic coma and finally we will also collect the value of the peak creatinine during the emission when embergliflozin is stopped on discharge or after 28 days clinical teams need to provide advice on changes to any other diabetes medications discharge documentation
Should include information on enrollment in the trial and the treatments given so other healthcare professionals are aware so in summary there is reason to think that sglt2 inhibitors such as epigloflosin may provide additional benefits to patients hospitalized with 9t the recovery trial is testing 10 milligrams once daily of ambiguity by up to 28 days the most
Important adverse effect of sglt2 inhibitors to be aware of is acidosis in patients with diabetes those at highest risk are excluded from the comparison such as type 1 diabetes whereas other diabetic patients who are allocated to ambiguity require regular ketone checks and actions to be taken if ketones rise thank you very much for your help with the recovery trial
Transcribed from video
RECOVERY Trial – Empagliflozin By Oxford Population Health
