Diuretic Treatment in Acute Heart Failure With Volume Overload Guided by Serial Spot Urine Sodium Assessment
Phase: PHASE4
Conditions: Acute Heart Failure, Diuretics Drug Reactions
Sponsor: Vrije Universiteit Brussel

 
 
 
 
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Study Protocol  
 
Study Title: 
Diuretic Treatment in Acute Heart Failure with Volume 
Overload Guided by Serial Spot Urine Sodium Assess-
ment 
Study Acronym: 
DECONGEST 
Phase of Development: 
IV 
Protocol Number: 
Study_Protocol_DECONGEST_v1.3 
Protocol Version and Date: 
Version 1.3, April 15, 2024 
EudraCT Registry Number:  
 
2021-005426-18 
ClinicTrials.gov Registry Number:  
NCT05411991 
Indication: 
 
 
 
 
Acute Heart Failure 
Investigational product: 
 
 
None 
Sponsor: 
 UZ Brussel 
Coordinating/Principal Investigator: 
 Prof. Dr. Frederik Verbrugge 
 
The information contained in this document is the property of the Sponsor/Coordinating Investiga-
tor and may not be reproduced, published or disclosed to others without written authorization of 
the Sponsor/Coordinating Investigator. 
PROTOCOL SIGNATURE PAGE 
Protocol Version and date:  
 
Version 1.3, April 15, 2024 
 
Protocol Title: 
Diuretic Treatment in Acute Heart Failure with Volume 
Overload Guided by Serial Spot Urine Sodium Assess-
ment 
 
Sponsor:  
 
 
 
UZ Brussel 
 
Principal Investigator:   
 
Prof. Dr. Frederik Verbrugge 
 
I agree: 
- 
to assume responsibility for the proper conduct of this study 
- 
to conduct the study in compliance with this protocol and any future amendments  
- 
not to implement any deviations from or changes to the protocol without prior review 
and written approval from the Ethics Committee, except where necessary to eliminate 
an immediate hazard to the subjects, or for administrative aspects of the study (where 
permitted by all applicable regulatory requirements) 
- 
that I am thoroughly familiar with the appropriate use of the investigational drug, as 
described in this protocol 
- 
to ensure that all persons assisting me with the study are adequately informed about 
the investigational drug and their study-related duties and functions as described in the 
protocol 
- 
that I am aware of and will comply with the current good clinical practice (GCP) guide-
lines and ethical principles outlined in the Declaration of Helsinki 
- 
to conduct the study in accordance with all applicable laws and regulations 
 
 
Printed name: Frederik Verbrugge 
 
Signature                                         Date: 22/04/2024 

 
 
 
 
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Study Protocol 
Diuretic Treatment in Acute Heart Failure with Volume Overload Guided 
by Serial Spot Urine Sodium Assessment (DECONGEST) study 
 
1. Primary investigator (PI) 
Dr. Frederik Verbrugge (Centrum voor Hart- en Vaatziekten, UZ Brussel) 
 
2. Study design 
 
Prospective 
 
Pragmatic 
 
Interventional 
 
Randomised 
 
Open label 
 
Multicentre (UZ Brussel & Jessa Hospital Hasselt) 
 
3. Purpose & rationale 
Signs and symptoms of volume overload are the most frequent reason for hospital admission 
in patients with heart failure.1 During such episodes of acute heart failure (AHF), diuretics are 
the mainstay treatment. Good diuretic efficiency with complete decongestion is associated 
with better outcomes.2 However, these targets remain challenging in clinical practice as diu-
retic resistance occurs frequently and a normal volume status cannot be readily assessed. 
This at least partly explains why clinical outcomes after an episode of AHF remain dismal, 
with recent European registry data demonstrating a 1-year rehospitalization rate of 44.4% 

 
 
 
 
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(25.9% for heart failure readmissions only) and all-cause mortality of 26.7%.3 Residual (sub-
)clinical congestion is likely an important mediator of this high risk.4 
Spot urine sodium assessment is a reliable indicator of diuretic response.5 Its use in AHF has 
been recommended by the new guidelines on heart failure of the European Society of Car-
diology, with the aim of detecting diuretic resistance early to allow appropriate treatment in-
tensification.6,7 A sodium concentration <50-70 mmol/L on a spot urine sample collected 
within the time window of diuretic activity (approximately 6 h after administration for intrave-
nous furosemide/bumetanide) indicates poor diuretic response. When confronted with poor 
diuretic response in the presence of persistent signs of volume overload, more intensive di-
uretic treatment (i.e., dose increase or combination therapy) and/or ultrafiltration are indi-
cated to ensure proper decongestion. 
In addition, observational data suggest that a high urine sodium concentration on spot urine 
sample after diuretic therapy indicates persistent congestion, even when clinical signs of vol-
ume overload are not obvious.5,8,9 Therefore, hypothetically, intensive diuretic therapy in AHF 
until complete disappearance of clinical signs of volume overload and a urine sodium con-
centration drop <80 mmol/L, with immediate step-up care in case of diuretic resistance (i.e., 
low urine sodium concentration with persistent signs of volume overload), may improve the 
quality of decongestion and potentially clinical outcomes. This study prospectively examines 
a systematic approach to diuretic therapy in AHF, based upon serial assessment of sodium 
concentration on spot urine samples after diuretic administration. 
 
 

 
 
 
 
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4. Objectives 
Primary objective: 
To investigate whether a diuretic regimen based on serial assessment of sodium concentration 
on spot urine samples after diuretic administration improves decongestion versus usual care in 
AHF, potentially leading to better clinical outcomes. 
 
Secondary objectives: 
 
To provide prospective longitudinal data on the incidence and determinants of diuretic re-
sistance in patients with AHF and low-threshold use of combinational diuretic treatment. 
 
To investigate the relationship between hemodynamic congestion (i.e., cardiac filling pres-
sures & diastolic function on transthoracic echocardiography) and urine sodium concentra-
tion under appropriately dosed diuretics according to a standardised regimen. 
 
To investigate the relationship between lung congestion (B-lines on lung ultrasound), as well 
as abdominal organ congestion (venous Doppler echography), and urine sodium concentra-
tion under appropriately dosed diuretics according to a standardised regimen. 
 
To compare diagnostic modalities for decongestion: urine sodium profiling, clinical examina-
tion, laboratory biomarkers, transthoracic echocardiography, lung ultrasound, and venous 
Doppler echocardiography. 
 
To investigate the relationship between right ventricular function, assessed by transthoracic 
echocardiography, and abdominal organ congestion, assessed by Doppler echography, as 
well as its evolution under decongestive treatment. 
 
To investigate the relationship between left atrial function, assessed by transthoracic echo-
cardiography, and urine sodium balance. 
 
 

 
 
 
 
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5. Study population 
Inclusion criteria: 
 
At least 18 y/o and able to provide informed consent 
 
Hospital admission (anticipated stay >24 h after randomisation) with diagnosis of 
AHF according to the treating physician 
 
At least one of the following three signs of volume overload: 
o bilateral oedema 2+, indicating clear pitting 
o ascites that is amenable for drainage, confirmed by echography (no obligation 
to perform abdominal echocardiography, but necessary when presence of 
ascites is used as an entry criterion for the study) 
o uni- or bilateral pleural effusions that are amenable for drainage, confirmed 
by chest X-ray or lung ultrasound (no obligation to perform chest X-ray, but 
necessary when presence of pleural effusions is used as an entry criterion for 
the study) 
 
Plasma N-terminal of the pro-hormone of B-type natriuretic peptide (NTproBNP) level 
>1,000 ng/L 
 
Exclusion criteria: 
 
No possibility to collect reliable urine spot samples after diuretic administration 
 
Administration of any diuretic within 6 h before randomisation, except for a mineralo-
corticoid receptor antagonist (MRA) or sodium-glucose co-transporter 2 (SGLT2) in-
hibitor as part of the patient’s maintenance treatment for heart failure. Patients can 
still be included in the DECONGEST study after withholding these diuretics for 6 h, 
after which randomisation can be performed if they qualify all other criteria. 

 
 
 
 
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 
Severe kidney dysfunction, defined as an estimated glomerular filtration rate (eGFR) 
<15 mL/min/1.73m² calculated by the Chronic Kidney Disease Epidemiology Collab-
oration (CKD-EPI) formula10 at randomisation, and/or previous, current, or planned 
future renal replacement therapy 
 
Systolic blood pressure <90 mmHg, mean arterial pressure <65 mmHg, or need for 
inotropes/vasopressor therapy at randomisation 
 
Any acute coronary syndrome within 30 days prior to enrolment, defined as typical 
chest pain with a troponin rise above the 99th percentile of normal and/or electrocar-
diographic changes suggestive of cardiac ischemia 
 
History of heart or kidney transplantation 
 
History of mechanical circulatory support 
 
Known obstructive hypertrophic cardiomyopathy, congenital heart disease, acute me-
chanical cause of AHF (e.g., papillary muscular rupture), acute myocarditis, or con-
strictive pericarditis according to the treating physician 
 
Pregnant or breastfeeding woman 
 
Concomitant participation in another interventional study 
 
6. Randomisation and allocation concealment 
Patients will be randomised through an online website using the Castor Electronic Data Cap-
ture system. Block randomisation will be performed, stratified for study centre and left ven-
tricular ejection fraction (<50% versus ≥50%) with variable blocks of 2 or 4 subjects for allo-
cation concealment. 
 
7. Control arm 
Usual care according to the treating physician. It is recommended to treating physicians to 
administer an intravenous loop diuretic dose at least twice a day (or through continuous in-
fusion), with the aim of achieving a urine output 3-5 L per day until the patient is considered 

 
 
 
 
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in an optimal volume status as is recommended by current guidelines.7 It is actively discour-
aged to switch from intravenous to oral diuretic therapy in the presence of persistent clinical 
signs of volume overload. Diuretic agents with their dose and administration method (bolus 
versus continuous infusion) are determined by the treating physician. It is recommended to 
keep disease-modifying treatments with angiotensin-converting enzyme inhibitors, angioten-
sin receptor blockers, angiotensin-neprilysin inhibitors, MRAs, and SGLT2 inhibitors un-
changed during the period of intravenous diuretic administration, although withdrawal or dose 
reduction in case of (relative) contraindications is allowed. Urine electrolyte assessment in 
the control arm is not allowed and qualifies as a major protocol violation as it is a key com-
ponent of the studied intervention. 
 
8. Intervention 
Diuretic administration after randomisation 
Immediately after randomisation, patients in the intervention arm receive an intravenous bo-
lus of bumetanide, with the dose depending on the eGFR: 2 mg for >45 mL/min/1.73m²; 3 mg 
for 45-30 mL/min/1.73m²; or 4 mg for <30 mL/min/1.73m². In addition, an intravenous bolus 
of 500 mg acetazolamide is administered unless hypernatremia (serum sodium concentra-
tion >145 mmol/L) or metabolic acidosis (serum bicarbonate <22 mmol/L) is present. Oral 
chlorthalidone 50 mg is added in case of hypernatremia (serum sodium concentration 
>145 mmol/L) or an eGFR <30 mL/min/1.73m². The patient is asked to void empty or, in case 
of a bladder catheter, any urine present at the time of initial diuretic administration is dis-
carded. A background maintenance infusion with 500 mL dextrose 5% and 3 g MgSO4 is 
started at an infusion rate of 20 mL/h and continued until switch to oral maintenance treat-
ment (see below). If serum potassium levels are <4 mmol/L at any time during administration 
of intravenous diuretics, 40 mmol KCl is added to this maintenance infusion. In case of sig-
nificant hyponatremia <130 mmol/L, the maintenance infusion is replaced by a daily bolus of 
3 g MgSO4. 

 
 
 
 
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Serial spot urine sodium assessment 
After every protocol-specified bolus administration of bumetanide, a spot urine sample is 
collected for assessment of sodium concentration and a subsequent treatment decision. The 
first urine within the period of 30 min to 3 h after bumetanide administration is used for anal-
ysis. 
 
Subsequent diuretic therapy guided by serial spot urine sodium assessment 
After the initial diuretic administration upon randomisation (Day 0), an intravenous bolus of 
bumetanide is provided twice daily on the next consecutive days. The dose for each bolus is 
as described above, based on the most recent eGFR value available. A minimal 6 h interval 
is respected between consecutive bumetanide administrations. Intravenous acetazolamide 
500 mg OD is provided together with the first bumetanide dose on any given day unless 
hypernatremia (serum sodium concentration >145 mmol/L) or metabolic acidosis (serum bi-
carbonate <22 mmol/L) is present. Oral chlorthalidone is continued at a dose of 50 mg OD 
in case that it was indicated upon randomisation (see above). 
If the spot urine sodium concentration following bumetanide administration is ≥80 mmol/L, 
the protocol continues with the next bumetanide bolus that is scheduled as described (com-
bined with acetazolamide and/or chlorthalidone as indicated). If the spot urine sodium con-
centration is <80 mmol/L, there are 2 possibilities: (1) the treating physician finds no clinical 
arguments for residual volume overload and there is no more than trace oedema, in which 
case the patient is switched from intravenous diuretics to oral maintenance therapy (see be-
low); or (2) there is residual volume overload and/or more than trace oedema, indicating 
diuretic resistance. In case of a missing urine sodium concentration because urine spot sam-
pling could not be performed, the previous bumetanide dose that has been administered is 
repeated. 
 

 
 
 
 
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Approach to diuretic resistance 
If the clinical exam and spot urine sodium assessment indicate diuretic resistance (i.e., so-
dium concentration <80 mmol/L with persistent volume overload), full nephron blockade is 
applied at the moment of the next scheduled bumetanide dose. The following combination 
therapy is administered: 
- 
Intravenous acetazolamide 500 mg as bolus, unless hypernatremia (serum sodium 
concentration >145 mmol/L) or metabolic acidosis (serum bicarbonate <22 mmol/L) 
- 
Intravenous bumetanide 4 mg as bolus 
- 
Oral chlorthalidone 100 mg 
- 
Intravenous potassium canrenoate 200 mg IV as bolus unless hyperkalaemia (serum 
potassium concentration >5 mmol/L). If the patient is already treated with an oral 
MRA as part of his/her maintenance therapy, this medication is paused until switch 
to oral maintenance treatment. 
The bumetanide dose is subsequently repeated after 6 h and 12 h (TID) in case of good 
diuretic response (i.e., spot urine sodium concentration ≥80 mmol/L). The entire combination 
is repeated after 24 h in case of good diuretic response. This schedule is continued until 
successful decongestion (spot urine sodium concentration <80 mmol/L and absence of vol-
ume overload with no more than trace oedema) or refractory volume overload with spot urine 
sodium concentration <80 mmol/L despite full nephron blockade. In the latter scenario, all 
diuretics are withdrawn and ultrafiltration with or without renal replacement therapy is started 
and continued according to the treating physician. 
 
Switch to oral maintenance therapy 
If urine sodium concentration is <80 mmol/L and the treating physician has no clinical argu-
ments for residual volume overload, with no more than trace oedema present, this is consid-
ered successful decongestion. Acetazolamide (and potassium canrenoate if it was indicated 

 
 
 
 
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according to the study protocol) are stopped. Chlorthalidone is continued at a dose of 50 mg 
OD only when it was previously added as part of full nephron blockade because of diuretic 
resistance. If chlorthalidone was started because of hypernatremia and/or low eGFR at ran-
domisation, it is withdrawn. Spironolactone 25 mg OD or an equivalent MRA is started (or 
continued) 
unless 
serum 
potassium 
levels 
are 
>5 mmol/L 
and/or 
eGFR 
is 
<20 mL/min/1.71m². Intravenous bumetanide is replaced by an oral loop diuretic with dose 
and administration frequency at the discretion of the treating physician. The maintenance 
dextrose 5% infusion is halted. 
 
Neurohumoral blocker treatment 
In the intervention group, it is obligatory to keep disease-modifying treatments with angioten-
sin-converting enzyme inhibitors, angiotensin receptor blockers, angiotensin-neprilysin inhib-
itors, MRAs, and SGLT2 inhibitors unchanged during the period of intravenous diuretic ad-
ministration, although withdrawal or dose reduction in case of (relative) contraindications is 
allowed. Dose up-titration or start of these treatments is allowed after transition from intrave-
nous to oral diuretic therapy and recommended in patients with reduced ejection fraction. 
 
 

 
 
 
 
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Intervention flowchart 
 
 
9. Safety precautions 
Anticipated adverse events, potentially related to the study intervention, include arterial hy-
potension, acute kidney injury (AKI) and electrolyte disorders. Arterial blood pressure is eval-
uated throughout the study protocol with continuous invasive measurements or frequent 
non-invasive assessment by cuff manometry. Serum creatinine, eGFR, and serum electrolyte 

 
 
 
 
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levels are followed on a daily base during the administration of intravenous diuretics accord-
ing to the study protocol and afterwards at the discretion of the treating physician. 
 
Arterial hypotension 
In case of significant arterial hypotension, defined as a systolic blood pressure <90 mmHg 
and/or mean arterial pressure <65 mmHg at any time during the period of intravenous diuretic 
therapy, all non-diuretic hypotensive medications are withdrawn and the next diuretic admin-
istration is postponed until blood pressure recovery. If use of vasopressors or inotropes is 
clinically indicated according to the treating physician as rescue therapy, the protocolised 
administration of diuretics is halted and further treatment is at the discretion of the treating 
physician. 
 
Acute kidney injury 
If the serum creatinine doubles (compared to its baseline value at randomisation) at any time 
during the period of intravenous diuretic therapy and has an absolute value >2 mg/dL, the 
protocolised administration of diuretics is halted and further treatment is at the discretion of 
the treating physician. 
 
Electrolyte disorders 
 
In case of clinically significant hyperkalaemia >5.5 mmol/L, any treatment with 
renin-angiotensin system blockers and/or MRAs is temporarily interrupted. If serum 
potassium levels rise further >6.5 mmol/L despite these precautions, the protocolised 
administration of diuretics is halted and further treatment is at the discretion of the 
treating physician. 
 
In case of hypokalaemia <3.5 mmol/L (despite administration of 40 mmol of daily KCl 
as specified above), oral supplementation is provided as necessary for correction, 
with target levels of serum potassium >4 mmol/L. 

 
 
 
 
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 
In case of hypotonic hyponatremia <135 mmol/L, chlorthalidone or potassium canren-
oate that is specified according to the study protocol is withheld and treatment with 
MRA is temporarily interrupted until restauration of a serum sodium level 
≥135 mmol/L. In patients with serum sodium levels <130 mmol/L, the hypotonic 
maintenance infusion will not be administered. In case of severe hyponatremia 
<125 mmol/L, a bolus of 150 mL hypertonic saline 3% is administered and repeated 
once daily if necessary, until sodium levels are ≥135 mmol/L. 
 
In case of hypernatremia >145 mmol/L, additional free water is administered as dex-
trose 5% to keep serum sodium levels ≤145 mmol/L and the patient will be allowed 
to have more liberal fluid intake if possible. 
 
In case of severe metabolic acidosis with serum bicarbonate levels <20 mmol/L, 
100 mL of intravenous NaHCO3 8.4% is administered. No further administration of 
acetazolamide is allowed during the entire study protocol in such cases. 
 
10. Study endpoints 
Primary study endpoint: 
The primary study endpoint is the win ratio for a hierarchically composed endpoint. The indi-
vidual components of this endpoint in order of importance are: 
1) Death within 30 days after discharge 
2) Number of days in hospital from the first 30 days after randomisation 
3) Relative NTproBNP decrease from baseline to 30 days after randomisation 
 
Secondary study endpoints: 
 
Relative NTproBNP decrease from baseline to 30 days after randomisation [%] 
 
Relative cancer antigen 125 (CA 125) from baseline to 30 days after randomisation 
[%] 
 
Length of intravenous diuretic therapy [days] 

 
 
 
 
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 
Successful decongestion defined as no more than trace oedema, absence of jugular 
venous distension and no rales upon the moment of transition from intravenous diu-
retics to oral maintenance therapy 
 
Five-point Likert scale for overall well-being assessed upon the transition from intra-
venous diuretics to oral maintenance therapy compared to the moment of randomi-
zation (much improved/slightly improved/neutral/slightly worse/much worse) 
 
Doubling of the serum creatinine or plasma cystatin C compared to baseline with an 
absolute value >2 mg/dL or >2 mg/L, respectively, or the need for ultrafiltration and/or 
renal replacement therapy during the index hospital admission (renal safety 
end-point) 
 
Systolic blood pressure <90 mmHg or mean arterial pressure <65 mmHg or need for 
vasopressors and/or inotropes during the index hospital admission (hemodynamic 
safety endpoint) 
 
Length of the index hospital admission [days] 
 
Death, non-elective rehospitalization or non-elective medical contact 
 
Death or non-elective hospital readmission rate 
 
Prespecified exploratory endpoints: 
 
Five-point Likert scale for overall well-being assessed at discharge and at 30 days 
after randomisation, compared to the moment of randomization (much im-
proved/slightly improved/neutral/slightly worse/much worse) 
 
Oedema score (1+: trace to 4+: above the knee) upon transition from intravenous 
diuretic towards oral maintenance therapy, at discharge, and at 30 days after ran-
domisation 
 
Weight change from baseline to switch towards oral maintenance therapy [kg] 
 
Cumulative intravenous loop diuretic dose administered according to the study proto-
col before transition towards oral maintenance therapy [mg bumetanide equivalents] 

 
 
 
 
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 
Weight change from baseline to switch towards oral maintenance therapy, adjusted 
for loop diuretic dose administered [kg per mg bumetanide equivalents] 
 
Relative NTproBNP change from baseline to switch towards oral maintenance ther-
apy [%] 
 
Relative CA 125 change from baseline to switch towards oral maintenance therapy 
[%] 
 
Change in eGFR (calculated according to the Chronic Kidney Diseases Collaboration 
formula with creatinine, cystatin C, and both) from baseline to switch towards oral 
maintenance therapy and to 30 days after randomisation 
 
Incidence of electrolyte disorders as described in the paragraph “Safety Precautions” 
(see above) during the phase of intravenous diuretic treatment 
 
Averaged medial/lateral E/e’ ratio on transthoracic echocardiography upon switch to-
wards oral maintenance therapy, at discharge, and at 30 days after randomisation 
 
Peak left atrial longitudinal strain on transthoracic echocardiography upon switch to-
wards oral maintenance therapy, at discharge, and at 30 days after randomisation 
[%] 
 
Tricuspid annular plane systolic excursion over right ventricular systolic pressure ratio 
on transthoracic echocardiography upon switch towards oral maintenance therapy, at 
discharge, and at 30 days after randomisation [mm/mmHg] 
 
Number of B-lines on lung ultrasound, scanning 8 thoracic sites upon switch towards 
oral diuretic regimen, at discharge, and at 30 days after randomisation11 
 
VExUS score for venous Doppler measurements as a marker for abdominal venous 
congestion upon switch towards oral diuretic regimen, at discharge, and at 30 days 
after randomisation12 
 
 

 
 
 
 
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11. Statistical analysis 
Power calculation: 
As the primary study end-point is anticipated to be driven mainly by the change in NTproBNP 
levels, the study is powered for that specific component of the primary end-point, which also 
constitutes the first secondary end-point. Assuming an average 75% relative decrease in 
NTproBNP levels at 30 days after discharge compared to baseline in the control group versus 
an 85% decrease in the intervention group, with a standard deviation of 15%, 94 patients 
need to be included given a significance level (alpha) of 0.05 to yield a statistical power 
(1-beta) of 90%. To account for potential drop-out up to 10%, the targeted study sample size 
is set at 104 subjects. 
 
Main statistical analysis: 
The primary analysis of the study assesses the win-ratio of the hierarchically composed pri-
mary end-point using the Finkelstein-Schoenfeld method.13 This method is based on the prin-
ciple that each subject in the study is compared to every other subject within each stratum in 
a pair-wise manner. This method gives the highest importance to all-cause mortality at 
30 days after discharge, subsequently to the number of days hospitalised during the 30 days 
after randomisation and finally to the relative change in NTproBNP levels at 30 days after 
randomisation compared to baseline. 
If the primary study endpoint is positive, secondary endpoints will be assessed in a hierar-
chical sequence without adjusting for multiple testing. If the primary endpoint or any of the 
secondary study endpoints is negative, all following endpoints will be considered explorative. 
Fisher’s Exact test, the independent-samples t-test and Mann-Whitney U test are used as 
indicated to assess the secondary endpoints. All primary study analyses will be performed 
according to the intention to treat principle. 
 
 

 
 
 
 
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12. Data collection 
A screening log with the relevant inclusion and exclusion criteria and the randomisation key 
will be obtained via the Castor Electronic Data Capture system. All other relevant study data 
will be collected and put in an online accessible Redcap database that is continuously up-
dated by the study researchers. All patients will get an appointment for an in-hospital study 
visit 30 days after randomisation (or are visited by a study person when they have a pro-
longed in-hospital stay >30 days during their index hospitalisation) to ensure complete data 
capturing. Patients who miss their appointment will be contacted by phone and e-mail to 
identify the reasons of not showing up and minimise loss of data. 
 
13. Timeline 
 
October
2021
• Obtain EudraCT number & FAGG approval
• Submission ethics committee UZ Brussel
March
2022
• Register study at clinicaltrials.gov
• Approval and start study at UZ Brussel
• Submission ethics committee at Jessa Hospital Hasselt
April
2022
• Activate study at Jessa Hospital Hasselt
JUNE
2024
• Estimated complete recruitment
August
2024
• Estimated study completion

 
 
 
 
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