Heart Failure
Conditions
Keywords
acetazolamide, bumetanide, cardio-renal syndrome, diuretics, heart failure, natriuresis, spironolactone
Brief summary
This study has two primary objectives: 1. To compare combination therapy with acetazolamide and low-dose loop diuretics versus high-dose loop diuretics (standard of care) in patients with acute decompensated heart failure at high risk for diuretic resistance. 2. To demonstrate the safety and efficacy of upfront therapy with spironolactone in addition to loop diuretic therapy in patients with acute decompensated heart failure at high risk for diuretic resistance.
Interventions
DRUGCombination therapy with acetazolamide and low-dose loop diuretics
* Patients receive 500 mg of intravenous acetazolamide immediately after randomization, with 250 mg intravenous acetazolamide administered on each consecutive day in the morning for as long as the patient is considered volume overloaded by his/her treating cardiologist. * Patients receive 2 mg of intravenous bumetanide immediately after randomization, with 1 mg intravenous bumetanide administered on each consecutive day in the morning for as long as the patient is considered volume overloaded by his/her treating cardiologist. * If diuresis \<1,5 L while the patient is still considered volume overloaded by his/her treating cardiologist, the dose of acetazolamide is maintained at 500 mg and the dose of bumetanide is maintained at 2mg. In case of therapy-refractory congestion, treatment is at the discretion of the treating physician, but addition of chlorthalidone 50 mg PO is recommended by the investigators as a first-line option.
DRUGHigh-dose loop diuretics
* Patients receive the double of their daily maintenance dose of oral loop diuretics converted to mg bumetanide as an intravenous bolus after randomization. * Patients continue to receive this dose daily on the next 3 days divided between two administrations with at least a 6 h interval for as long as they are considered volume overloaded by the treating cardiologist. * If diuresis \<1,5 L while the patient is still considered volume overloaded by the treating cardiologist, the dose of bumetanide is doubled. In case of therapy-refractory congestion, treatment is at the discretion of the treating physician, but addition of chlorthalidone 50 mg PO is recommended by the investigators as a first-line option.
DRUGUpfront therapy with oral spironolactone
Patients randomized to this group receive oral spironolactone (25mg) immediately after randomization and in the morning of each subsequent day unless the serum potassium level is \>5 mmol/L. Note: Investigators and treating physicians are blinded to treatment allocation for this arm, but no matching placebo is provided, so patients are not.
Sponsors
Ziekenhuis Oost-Limburg
Universitaire Ziekenhuizen KU Leuven
Hasselt University
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
TREATMENT
Masking
TRIPLE (Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Older than 18 years and able to give informed consent * Clinical diagnosis of acute decompensated heart failure within the previous 8 h * At least two clinical signs of congestion (edema, ascites, jugular venous distension, or pulmonary vascular congestion on chest radiography) * Maintenance therapy with oral loop diuretics at a dose of at least 1 mg bumetanide (1 mg bumetanide = 40 mg furosemide = 20 mg torsemide) for at least 1 month before hospital admission * NT-proBNP \>1000 ng/L * Left ventricular ejection fraction \<50% * At least one out of three of the following criteria: * Serum sodium \<136 mmol/L * Serum urea/creatinine ratio \>50 (comparable to a BUN/creatinine ratio \>25) * Admission serum creatinine increased with \>0.3 mg/dL compared to previous value within 3 months before admission
Exclusion criteria
* History of cardiac transplantation and/or ventricular assist device * Concurrent diagnosis of an acute coronary syndrome defined as typical chest pain and/or electrocardiographic changes in addition to a troponin rise \>99th percentile * Mean arterial blood pressure \<65 mmHg, or systolic blood pressure \<90 mmHg at the moment of admission * Use of intravenous inotropes, vasopressors or nitroprusside at any time point during the study * A baseline estimated glomerular filtration rate \<15 mL/min/1.73m² according to the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula at the moment of inclusion * Use of renal replacement therapy or ultrafiltration before study inclusion * Treatment with acetazolamide within the previous month * Treatment with ≥2 mg bumetanide or an equivalent dose during the index hospitalization before randomization * Use of diuretics, vasopressin antagonists or mineralocorticoid receptor antagonist not specified by the protocol * Exposure to nephrotoxic agents (i.e. contrast dye) anticipated within 3 days
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Acetazolamide Arm: Natriuresis 24 h | 24h | For the acetazolamide arm of the study, the primary end-point is total natriuresis after 24 h (mmol). To assess this, urine is collected for 24 h after the first administration of diuretics according to the study protocol and natriuresis is calculated as the total amount of diuresis (L) multiplied by the urinary sodium concentration (mmol/L). Subsequently, patients receiving acetazolamide and low-dose loop diuretics (both the groups with and without upfront spironolactone together) are compared to patients not receiving acetazolamide but high-dose loop diuretics instead (both the groups with or without upfront spironolactone together) |
| Spironolactone Arm: Incidence of Hypo- (Serum Potassium <3.5 mmol/L) or Hyperkalemia (Serum Potassium >5.0 mmol/L) | 72h | For the spironolactone arm of the study, the primary end-point is the incidence of either hypo- (serum potassium \<3.5 mmol/L) or hyperkalemia (serum potassium \>5.0 mmol/L) at any of 3 morning blood samples at consecutive days after randomization. Patients receiving upfront spironolactone (both the group receiving acetazolamide+low dose loop diuretics and the group receiving high-dose loop diuretic therapy) are compared with them receiving no spironolactone (both the group receiving acetazolamide+low dose loop diuretics and the group receiving high-dose loop diuretic therapy). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Persistent Renal Impairment | 4 weeks after hospital discharge | Persistent renal impairment is defined as a persistently elevated serum creatine \>0.3mg/dL or \>20% decrease in estimated glomerular filtration rate by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula, above the baseline value of the patient and will be assessed on a scheduled follow-up appointment 4 weeks after hospital discharge. |
| NT-proBNP Change After 72 h | 72h | Relative NT-proBNP change (%) after 72 h compared to baseline. |
| Peak Plasma Renin Activity After 72 h | 72h | At three consecutive mornings after study inclusion, blood samples will be taken to assess plasma renin activity. The highest value will constitute the peak plasma renin activity (ng/mL/h). |
| Peak Plasma Aldosterone Concentration After 72 h | 72h | At three consecutive mornings after study inclusion, blood samples will be taken to assess plasma aldosterone levels. The highest value will constitute the peak plasma aldosterone concentration (ng/L). |
| Number of Participants With Worsening Renal Function | 72h | Worsening renal function is defined as a rise in serum creatine \>0.3 mg/dL or a \>20% decrease in estimated glomerular filtration rate by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula compared to baseline at any time point before 72 h. Serum creatinine values are assessed at three consecutive mornings after study inclusion. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Visual Analogue Scale Score for Dyspnea After 48 h | 48h | — |
| Visual Analogue Scale Score for Dyspnea After 72 h | 72h | — |
| 4-point Likert Scale for Edema After 24 h | 24h | — |
| Natriuresis 48 h | 48h | Total natriuresis (mmol) after 48 h. |
| 4-point Likert Scale for Edema After 72 h | 72h | — |
| Incidence of Therapy-refractory Congestion | 72h | Need for combinational diuretic therapy with thiazide-type diuretics, bail-out ultrafiltration or renal replacement therapy |
| All-cause Mortality | After 1 year of follow-up | — |
| 4-point Likert Scale for Edema After 48 h | 48h | — |
| Natriuresis 72 h | 72h | Total natriuresis (mmol) after 72 h. |
| Diuresis 24 h | 24h | Total amount of urine output (L) after 24 h. |
| Diuresis 48 h | 48h | Total amount of urine output (L) after 48 h. |
| Diuresis 72 h | 72h | Total amount of urine output (L) after 72 h. |
| Weight Change After 72 h | 72h | Body weight change after 72 h compared to admission. |
| Visual Analogue Scale Score for Dyspnea After 24 h | 24h | Scale name and construct: Visual analogue scale presented as a line with a movable indicator. Far left of the line indicates no dyspnea at all and far right of the line indicates the worst imaginable dyspnea. The participant can move the indicator to one certain point among the line and the investigator can read at the back a number going from 0 to 100 with 0 indicating no dyspnea and 100 the worst imaginable dyspnea. |
Countries
Belgium
Participant flow
Recruitment details
* Dates of the recruitment period: 28/12/2013 till 14/03/2017 * location: emergency services and outpatient cardiology clinic of 2 tertiary care centers (Ziekenhuis Oost-Limburg, Genk, Belgium & UZ Leuven, Leuven, Belgium)
Pre-assignment details
None, every patient that was enrolled was immediately randomised and started with the protocol of the study.
Participants by arm
| Arm | Count |
|---|---|
| Acetazolamide/Low-dose Loop Diuretics, Upfront Spironolactone * Patients receive 500 mg of intravenous acetazolamide immediately after randomization, with 250 mg intravenous acetazolamide administered on each consecutive day in the morning for as long as the patient is considered volume overloaded by his/her treating cardiologist.
* Patients receive 2 mg of intravenous bumetanide immediately after randomization, with 1 mg intravenous bumetanide administered on each consecutive day in the morning for as long as the patient is considered volume overloaded by his/her treating cardiologist.
* Patients receive open-label oral spironolactone at a dose of 25 mg unless serum potassium levels are \>5 mmol/L. | 9 |
| High-dose Loop Diuretics, Upfront Spironolactone * Patients receive the double of their daily maintenance dose of oral loop diuretics converted to mg bumetanide as an intravenous bolus after randomization.
* Patients continue to receive this dose daily on the next 3 days divided between two administrations with at least a 6 h interval for as long as they are considered volume overloaded by the treating cardiologist.
* Patients receive open-label oral spironolactone at a dose of 25 mg unless serum potassium levels are \>5 mmol/L. | 7 |
| Acetazolamide/Low-dose Loop Diuretics, no Spironolactone * Patients receive 500 mg of intravenous acetazolamide immediately after randomization, with 250 mg intravenous acetazolamide administered on each consecutive day in the morning for as long as the patient is considered volume overloaded by his/her treating cardiologist.
* Patients receive 2 mg of intravenous bumetanide immediately after randomization, with 1 mg intravenous bumetanide administered on each consecutive day in the morning for as long as the patient is considered volume overloaded by his/her treating cardiologist.
* Spironolactone use is prohibited during the first 72 h, but encouraged at discharge | 9 |
| High-dose Loop Diuretics, no Spironolactone * Patients receive the double of their daily maintenance dose of oral loop diuretics converted to mg bumetanide as an intravenous bolus after randomization.
* Patients continue to receive this dose daily on the next 3 days divided between two administrations with at least a 6 h interval for as long as they are considered volume overloaded by the treating cardiologist.
* Spironolactone use is prohibited during the first 72 h, but encouraged at discharge | 9 |
| Total | 34 |
Baseline characteristics
| Characteristic | High-dose Loop Diuretics, Upfront Spironolactone | Acetazolamide/Low-dose Loop Diuretics, Upfront Spironolactone | Total | High-dose Loop Diuretics, no Spironolactone | Acetazolamide/Low-dose Loop Diuretics, no Spironolactone |
|---|---|---|---|---|---|
| Age, Continuous | 75 years STANDARD_DEVIATION 7 | 81 years STANDARD_DEVIATION 8 | 80 years STANDARD_DEVIATION 7 | 81 years STANDARD_DEVIATION 7 | 81 years STANDARD_DEVIATION 5 |
| Beta-blocker therapy | 7 Participants | 8 Participants | 31 Participants | 8 Participants | 8 Participants |
| Estimated glomerular filtration rate | 32 mL/min/1.73m² STANDARD_DEVIATION 9 | 36 mL/min/1.73m² STANDARD_DEVIATION 17 | 36 mL/min/1.73m² STANDARD_DEVIATION 20 | 40 mL/min/1.73m² STANDARD_DEVIATION 31 | 35 mL/min/1.73m² STANDARD_DEVIATION 16 |
| History of atrial fibrillation | 4 Participants | 3 Participants | 20 Participants | 6 Participants | 7 Participants |
| History of diabetes | 2 Participants | 3 Participants | 10 Participants | 3 Participants | 2 Participants |
| History of ischemic heart disease | 6 Participants | 5 Participants | 21 Participants | 7 Participants | 3 Participants |
| New York Heart Association functional class II | 0 Participants | 2 Participants | 3 Participants | 1 Participants | 0 Participants |
| New York Heart Association functional class III | 3 Participants | 5 Participants | 19 Participants | 4 Participants | 7 Participants |
| New York Heart Association functional class IV | 4 Participants | 2 Participants | 12 Participants | 4 Participants | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 7 Participants | 9 Participants | 34 Participants | 9 Participants | 9 Participants |
| Region of Enrollment Belgium | 7 Participants | 9 Participants | 34 Participants | 9 Participants | 9 Participants |
| Renin-angiotensin blocker therapy | 4 Participants | 2 Participants | 14 Participants | 3 Participants | 5 Participants |
| Sex: Female, Male Female | 2 Participants | 2 Participants | 12 Participants | 3 Participants | 5 Participants |
| Sex: Female, Male Male | 5 Participants | 7 Participants | 22 Participants | 6 Participants | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 6 / 9 | 5 / 7 | 5 / 9 | 5 / 9 |
| other Total, other adverse events | 6 / 9 | 4 / 7 | 7 / 9 | 5 / 9 |
| serious Total, serious adverse events | 3 / 9 | 5 / 7 | 2 / 9 | 3 / 9 |
Outcome results
Primary
Acetazolamide Arm: Natriuresis 24 h
For the acetazolamide arm of the study, the primary end-point is total natriuresis after 24 h (mmol). To assess this, urine is collected for 24 h after the first administration of diuretics according to the study protocol and natriuresis is calculated as the total amount of diuresis (L) multiplied by the urinary sodium concentration (mmol/L). Subsequently, patients receiving acetazolamide and low-dose loop diuretics (both the groups with and without upfront spironolactone together) are compared to patients not receiving acetazolamide but high-dose loop diuretics instead (both the groups with or without upfront spironolactone together)
Time frame: 24h
Population: 2 patients not analysed because of errors with 24 h urinary collection
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Acetazolamide/Low-dose Loop Diuretics, Upfront Spironolactone | Acetazolamide Arm: Natriuresis 24 h | 324 mmol | Standard Deviation 133 |
| High-dose Loop Diuretics, Upfront Spironolactone | Acetazolamide Arm: Natriuresis 24 h | 300 mmol | Standard Deviation 165 |
| Acetazolamide/Low-dose Loop Diuretics, no Spironolactone | Acetazolamide Arm: Natriuresis 24 h | 211 mmol | Standard Deviation 96 |
| High-dose Loop Diuretics, no Spironolactone | Acetazolamide Arm: Natriuresis 24 h | 190 mmol | Standard Deviation 91 |
Comparison: 2x2 factorial design: both acetazolamide groups together are compared with both high-dose loop diuretic groups togetherp-value: 0.51595% CI: [-63, 123]t-test, 2 sided
Primary
Spironolactone Arm: Incidence of Hypo- (Serum Potassium <3.5 mmol/L) or Hyperkalemia (Serum Potassium >5.0 mmol/L)
For the spironolactone arm of the study, the primary end-point is the incidence of either hypo- (serum potassium \<3.5 mmol/L) or hyperkalemia (serum potassium \>5.0 mmol/L) at any of 3 morning blood samples at consecutive days after randomization. Patients receiving upfront spironolactone (both the group receiving acetazolamide+low dose loop diuretics and the group receiving high-dose loop diuretic therapy) are compared with them receiving no spironolactone (both the group receiving acetazolamide+low dose loop diuretics and the group receiving high-dose loop diuretic therapy).
Time frame: 72h
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Acetazolamide/Low-dose Loop Diuretics, Upfront Spironolactone | Spironolactone Arm: Incidence of Hypo- (Serum Potassium <3.5 mmol/L) or Hyperkalemia (Serum Potassium >5.0 mmol/L) | 1 Participants |
| High-dose Loop Diuretics, Upfront Spironolactone | Spironolactone Arm: Incidence of Hypo- (Serum Potassium <3.5 mmol/L) or Hyperkalemia (Serum Potassium >5.0 mmol/L) | 2 Participants |
| Acetazolamide/Low-dose Loop Diuretics, no Spironolactone | Spironolactone Arm: Incidence of Hypo- (Serum Potassium <3.5 mmol/L) or Hyperkalemia (Serum Potassium >5.0 mmol/L) | 5 Participants |
| High-dose Loop Diuretics, no Spironolactone | Spironolactone Arm: Incidence of Hypo- (Serum Potassium <3.5 mmol/L) or Hyperkalemia (Serum Potassium >5.0 mmol/L) | 2 Participants |
Comparison: 2x2 factorial design: analysis according to spironolactone usep-value: 0.27Fisher Exact
Secondary
NT-proBNP Change After 72 h
Relative NT-proBNP change (%) after 72 h compared to baseline.
Time frame: 72h
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Acetazolamide/Low-dose Loop Diuretics, Upfront Spironolactone | NT-proBNP Change After 72 h | -20 percentage change from baseline | Standard Deviation 36 |
| High-dose Loop Diuretics, Upfront Spironolactone | NT-proBNP Change After 72 h | -11 percentage change from baseline | Standard Deviation 19 |
| Acetazolamide/Low-dose Loop Diuretics, no Spironolactone | NT-proBNP Change After 72 h | -3 percentage change from baseline | Standard Deviation 40 |
| High-dose Loop Diuretics, no Spironolactone | NT-proBNP Change After 72 h | -6 percentage change from baseline | Standard Deviation 51 |
Secondary
Number of Participants With Worsening Renal Function
Worsening renal function is defined as a rise in serum creatine \>0.3 mg/dL or a \>20% decrease in estimated glomerular filtration rate by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula compared to baseline at any time point before 72 h. Serum creatinine values are assessed at three consecutive mornings after study inclusion.
Time frame: 72h
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Acetazolamide/Low-dose Loop Diuretics, Upfront Spironolactone | Number of Participants With Worsening Renal Function | 2 Participants |
| High-dose Loop Diuretics, Upfront Spironolactone | Number of Participants With Worsening Renal Function | 0 Participants |
| Acetazolamide/Low-dose Loop Diuretics, no Spironolactone | Number of Participants With Worsening Renal Function | 3 Participants |
| High-dose Loop Diuretics, no Spironolactone | Number of Participants With Worsening Renal Function | 0 Participants |
Secondary
Peak Plasma Aldosterone Concentration After 72 h
At three consecutive mornings after study inclusion, blood samples will be taken to assess plasma aldosterone levels. The highest value will constitute the peak plasma aldosterone concentration (ng/L).
Time frame: 72h
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Acetazolamide/Low-dose Loop Diuretics, Upfront Spironolactone | Peak Plasma Aldosterone Concentration After 72 h | 196 ng/L |
| High-dose Loop Diuretics, Upfront Spironolactone | Peak Plasma Aldosterone Concentration After 72 h | 234 ng/L |
| Acetazolamide/Low-dose Loop Diuretics, no Spironolactone | Peak Plasma Aldosterone Concentration After 72 h | 302 ng/L |
| High-dose Loop Diuretics, no Spironolactone | Peak Plasma Aldosterone Concentration After 72 h | 204 ng/L |
Secondary
Peak Plasma Renin Activity After 72 h
At three consecutive mornings after study inclusion, blood samples will be taken to assess plasma renin activity. The highest value will constitute the peak plasma renin activity (ng/mL/h).
Time frame: 72h
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Acetazolamide/Low-dose Loop Diuretics, Upfront Spironolactone | Peak Plasma Renin Activity After 72 h | 3.8 µg/L/h |
| High-dose Loop Diuretics, Upfront Spironolactone | Peak Plasma Renin Activity After 72 h | 5.0 µg/L/h |
| Acetazolamide/Low-dose Loop Diuretics, no Spironolactone | Peak Plasma Renin Activity After 72 h | 12.0 µg/L/h |
| High-dose Loop Diuretics, no Spironolactone | Peak Plasma Renin Activity After 72 h | 2.5 µg/L/h |
Secondary
Persistent Renal Impairment
Persistent renal impairment is defined as a persistently elevated serum creatine \>0.3mg/dL or \>20% decrease in estimated glomerular filtration rate by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula, above the baseline value of the patient and will be assessed on a scheduled follow-up appointment 4 weeks after hospital discharge.
Time frame: 4 weeks after hospital discharge
Population: 9 patients died or were too sick for follow-up appointment; 9 refused a venous blood sample at the follow-up appointment (protocol violation)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Acetazolamide/Low-dose Loop Diuretics, Upfront Spironolactone | Persistent Renal Impairment | 3 Participants |
| High-dose Loop Diuretics, Upfront Spironolactone | Persistent Renal Impairment | 1 Participants |
| Acetazolamide/Low-dose Loop Diuretics, no Spironolactone | Persistent Renal Impairment | 0 Participants |
| High-dose Loop Diuretics, no Spironolactone | Persistent Renal Impairment | 1 Participants |
Other Pre-specified
4-point Likert Scale for Edema After 24 h
Time frame: 24h
Other Pre-specified
4-point Likert Scale for Edema After 48 h
Time frame: 48h
Other Pre-specified
4-point Likert Scale for Edema After 72 h
Time frame: 72h
Other Pre-specified
All-cause Mortality
Time frame: After 1 year of follow-up
Other Pre-specified
Diuresis 24 h
Total amount of urine output (L) after 24 h.
Time frame: 24h
Other Pre-specified
Diuresis 48 h
Total amount of urine output (L) after 48 h.
Time frame: 48h
Other Pre-specified
Diuresis 72 h
Total amount of urine output (L) after 72 h.
Time frame: 72h
Other Pre-specified
Incidence of Therapy-refractory Congestion
Need for combinational diuretic therapy with thiazide-type diuretics, bail-out ultrafiltration or renal replacement therapy
Time frame: 72h
Other Pre-specified
Natriuresis 48 h
Total natriuresis (mmol) after 48 h.
Time frame: 48h
Other Pre-specified
Natriuresis 72 h
Total natriuresis (mmol) after 72 h.
Time frame: 72h
Other Pre-specified
Visual Analogue Scale Score for Dyspnea After 24 h
Scale name and construct: Visual analogue scale presented as a line with a movable indicator. Far left of the line indicates no dyspnea at all and far right of the line indicates the worst imaginable dyspnea. The participant can move the indicator to one certain point among the line and the investigator can read at the back a number going from 0 to 100 with 0 indicating no dyspnea and 100 the worst imaginable dyspnea.
Time frame: 24h
Other Pre-specified
Visual Analogue Scale Score for Dyspnea After 48 h
Time frame: 48h
Other Pre-specified
Visual Analogue Scale Score for Dyspnea After 72 h
Time frame: 72h
Other Pre-specified
Weight Change After 72 h
Body weight change after 72 h compared to admission.
Time frame: 72h