The Answers You Need
How do you ensure that the 24h oral intake of sodium is restricted to 1.5g?
1.5g sodium is the equivalent of 3.6g salt in the diet. Therefore, we recommend that patients are kept on a low-salt diet (2 to 3g salt). However, it needs to be stated that this background therapy is rather a recommendation than an obligation. If this recommendation is pragmatically not feasible in your centre, this will not jeopardize the conduct of this trial.
Is it also recommended to provide a maintenance infusion with 500ml glucose 5% to patients suffering from diabetes?
Yes. It is recommended to follow the proposed background therapy, yet, it is not obligated. Nonetheless, it should be stressed that an infusion with NaCl as background therapy should be avoided.
Is it necessary to perform an X-Ray or echography each day?
If the patient is assessed at screening with pleural effusion/ascites that is confirmed by chest X-ray and/or echography, the chest X-ray and/or echography should be repeated until day 4 or until pleural effusion/ascites has been confirmed to have disappeared by chest X-ray and/or echography. If not present at inclusion, new evidence of pleural effusion and/or ascites may arise during the treatment phase, but if scored, it should be confirmed by a chest X-ray or echography. If the patient is not volume overloaded anymore, the intravenous administration of study medication should be stopped. Once decongestion is achieved (volume assessment score ≤ 1) during the treatment phase, no volumeassessment should be performed the following morning. After the treatment phase, it is mandatory to perform a volume assessment at discharge and at follow-up. It is recommended to perform a chest X-ray or echography in case of clinical signs of pleural effusion or ascites, yet, it will be left to the discretion of the treating physician.
What is the maximal allowed dose of burinex?
The maximal allowed IV bolus dose of burinex is 5mg, which is in accordance with 200mg furosemide.
Does the start dose changes whenever a patient already receives loop diuretics at the emergency department?
No. The start dose of loop diuretics is independent of the dose received during index hospitalization before randomization, and its calculation is only based on the orally home dose. In other words, the start dose should not be adapted if the patient already received loop diuretics during the index hospitalization.
As it is an exclusion criteria, it is of utmost importance that patients should not have received more than 2mg bumetanide IV or an equivalence of another IV loop diuretic during the index hospitalization (e.g. at the emergency department).
Can the patient receive Aldactone/Eplerenon?
Aldactone (generic name Spironolacton) and Eplerenon are part of the group “Diuretics”, type “MRA”. Per protocol all non-protocol defined diuretics need to be stopped at time of entry into the study. Mineralocortoid receptor antagonists (MRAs) are an exception to this guideline.
If MRAs (like Aldactone) are chronically taken by the subject at time of entry in the study, intake can continue at the same or at a lower dose at the discretion of the treating physician. Dose increases are not allowed during the screening and treatment phase with the exception in case of hypokalaemia despite intravenous potassium supplement. After decongestion, it is strongly recommended to up-titrate the dose.
What has to be the home dose of oral loop diuretics in order to be eligible?
In order to be eligible for the ADVOR study, a patient should have a maintenance therapy with oral loop diuretics at a dose of at least 1 mg bumetanide or an equivalent dose for at least 1 month before hospital admission (Conversion: 1 mg bumetanide = 40 mg furosemide = 20 mg torsemide). For example, if the patient does not take oral loop diuretics on a daily basis, but every other day OR every other day a different dose, the mean daily dose needs to be calculated. This mean daily dose has to be at least 1 mg bumetanide (or equivalent dose) in order to be eligible.
If the oral daily maintenance dose has changed over the week prior to randomization, it will be defined as the highest orally administered daily dose that the patient has received in an outpatient context 3 days prior to randomization.