Cardiorenal Syndrome
Conditions
Brief summary
In double-blind clinical trial, determine renal recovery with two different furosemide strategies in patients with type 1 cardiorenal syndrome.
Detailed description
In a patient with type 1 cardiorenal syndrome, we tried to compare two Furosemide strategies: both with a morning bolus, and randomized in two groups: Group A: Furosemide 80 mg every 24 hrs (morning) intravenously every 24 hrs for 4 consecutive days, additionally: * Day 1 furosemide 100mg / day infused with 100cc of Hartmann solution * Day 2 Furosemide 200mg / day infused with 100cc of Hartmann solution * Day 3 Furosemide 300mg / day infused with 100cc of Hartmann solution * Day 4 Furosemide 400mg / day infused with 100cc of Hartmann solution Group B: Furosemide 80 mg every 24 hrs (morning) intravenously every 24 hrs for 4 consecutive days, additionally: * Day 1 furosemide 100mg / day infused with 100cc of Hartmann solution + Chlortalidone 50mg VO every 24 hours + Spironolactone 50mg VO every 24 hrs. * Day 2 furosemide 100mg / day infused with 100cc of Hartmann solution + Chlortalidone 50mg VO every 24 hours + Spironolactone 50mg VO every 24 hrs. * Day 3 furosemide 100mg / day infused with 100cc of Hartmann solution + Chlortalidone 50mg VO every 24 hours + Spironolactone 50mg VO every 24 hrs. * Day 4 furosemide 100mg / day infused with 100cc of Hartmann solution + Chlortalidone 50mg VO every 24 hours + Spironolactone 50mg VO every 24 hrs. ution + Chlortalidone 50mg VO every 24 hours + Spironolactone 25mg VO every 24 hrs. With the primary objective of improving renal function measured by serum creatinine, as secondary objectives the efficacy in vascular decongestion and electrolyte alterations.
Interventions
Administrated as an 80 mg intravenous bolus every 24 hours in both arms and then as a continuous infusion dosed according to the experimental arm.
DRUGChlortalidone
One 50 mg pill administrated every 24 hours in group B
DRUGSpironolactone
One 50 mg pill administrated every 24 hours in group B
Sponsors
Hospital Civil de Guadalajara
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
Double-blind clinical trial
Intervention model description
Its a randomized, controlled, phase II, 2-arm, double-blind clinical trial
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Comply with both clinical diagnosis of acute kidney injury by serum creatinine according to the Kidney Disease Improving Global Outcomes (KDIGO) 2012 guidelines and acute decompensate heart failure as clinical assessed by the clinical team in charge. * Have agreed and signed informed consent
Exclusion criteria
* Patient in chronic dialysis either peritoneal dialysis or hemodialysis. * History of being a renal transplant recipient * History of acute kidney injury according to the KDIGO 2012 guidelines and / or renal replacement therapy in the last 3 months * Pregnancy * Impossibility to administer medication by the oral route
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Renal Function Recovery Defined as a Return to Individual Baseline Serum Creatinine Values | Up to 96 hours after intervention started | Comparing patient's baseline serum creatinine (previous serum creatinine of 3 months ago and up to a year ago) with creatinine measurements every 24 hours during intervention (4 days) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Serum Creatinine at Day One of Intervention From Serum Creatinine at 96 Hrs After Intervention Started | 96 hours after intervention started | Calculated as serum creatinine at day one minus serum creatinine at 96 hrs after intervention started |
| An Elevation of at Least 0.3 mg/dl of Serum Creatinine From Day One of Intervention Compared With Serum Creatinine at 96hrs After Intervention Started | 96 hours after intervention started | — |
| In Hospital Mortality Defined as Number of Dead Patients From Day One of Intervention and Before Discharge | From day one of intervention up to discharge, an average of 1 week | — |
| Mortality During Follow up Defined as Number of Dead Patients After Discharge | From day one after discharge up to an average of 161 days | — |
| Change in 24 Hour Urine Output at 96 Hours After Intervention Started From 24 Hour Urine Output One Day Before Intervention Initiation) | 96 hours after intervention started | Urine output was collected through an urinary catheter and measured and registered by a nurse. The sum of these registrations from 7 am from one day to 7 am of the next day was considered the 24 hour urinary output |
| Number of Patients With Dyspnea Improvement as Referred by the Patient or Reduction in Supplementary Oxygen Requirements Before Day 3 of Intervention | Up to 3 days after intervention started | Dyspnea improvement was referred by the patient as the clinician asked them do you feel more or less difficult to breathe? or if the liters per minute or the fraction of inspired supplementary oxygen necessary maintain an oxygen saturation \>90% were diminished |
| Number of Days From the Beginning of the Intervention Until Patients Referred Dyspnea Improvement or a Reduction in Supplementary Oxygen Requirements Was Made. | Up to 4 days after intervention started | Dyspnea improvement was referred by the patient as the clinician asked them do you feel more or less difficult to breathe? or if the liters per minute or the fraction of inspired supplementary oxygen necessary maintain an oxygen saturation \>90% were diminished |
| Number of Patients That Required Renal Replacement Therapy of Any Type During Intervention (4 Days). | Up to 96 hours after intervention started | The requirement of renal replacement therapy was assessed by the nephrology team in charge |
| Number of Patients With Dyspnea Improvement as Referred by the Patient or Reduction in Supplementary Oxygen Requirements at 96 Hours After Intervention Started | Up to 96 hours after intervention started | Dyspnea improvement was referred by the patient as the clinician asked them do you feel more or less difficult to breathe? or if the liters per minute or the fraction of inspired supplementary oxygen necessary to maintain an oxygen saturation \>90% were diminished |
Other
| Measure | Time frame | Description |
|---|---|---|
| Change in Serum pH Value Measured at Day One of Intervention From Serum pH Value Measured at 96 Hrs After Intervention Started. | 96 hours after intervention started | Calculated as serum pH value at day one of intervention minus serum pH value at 96 hrs after intervention started. |
| Change in Serum Bicarbonate Levels Measured at Day One of Intervention From Serum Bicarbonate Levels Measured at 96 Hrs After Intervention Started. | 96 hours after intervention started | Calculated as serum bicarbonate levels at day one of intervention minus bicarbonate levels at 96 hrs after intervention started. |
| Change in Serum Copeptin Levels at Day One of Intervention From Serum Copeptin Levels Measured at 96 Hrs After Intervention Started. | 96 hours after intervention started | Calculated as serum copeptin levels at day one minus serum copeptin levels measured at 96 hrs after intervention started |
| Change in Serum Lactate Levels Measured at Day One of Intervention From Serum Lactate Levels Measured at 96 Hrs After Intervention Started. | 96 hours after intervention started | Calculated as serum lactate levels at day one of intervention minus serum lactate levels at 96 hrs after intervention started. |
| Change in Serum Partial Pressure of Carbon Dioxide Measured at Day One of Intervention From Serum Partial Pressure of Carbon Dioxide Measured at 96 Hrs After Intervention Started. | 96 hours after intervention started | Calculated as serum partial pressure of carbon dioxide at day one of intervention minus serum partial pressure of carbon dioxide at 96 hrs after intervention started. |
| Change in Serum Brain Natriuretic Peptide Levels at Baseline From Serum Brain Natriuretic Peptide Levels at 96 Hours After Intervention Started | 96 hours after intervention started | Baseline levels were defined as the measurement at hospital admission. Calculated as serum brain natriuretic peptide levels at baseline minus serum brain natriuretic peptide levels at 96 hours after intervention started |
| Number of Patients That Achieved >30% Reduction in Brain Natriuretic Compared With Baseline Levels | Up to 96 hours after intervention started | Baseline levels were defined as the measurement at hospital admission |
| Number of Patients Whose Interventions Were Stopped Because Clinical Improvement Was Achieved Before 96 Hours as Assessed by de Clinical Judgement of the Medical Team in Charge. | From the beginning of intervention and before 96 hours after that | Clinical improvement was referred as remission of symptoms with achievement of 24 hour urine output equal or greater than 3000 milliliters |
| Change in Serum Urea Levels Measured at Day One of Intervention From Serum Urea Levels Measured at 96 Hrs After Intervention Started. | 96 hours after intervention started | Calculated as serum urea levels at day one of intervention minus serum urea levels at 96 hrs after intervention started. |
| Change in Serum Sodium Levels Measured at Day One of Intervention From Serum Sodium Levels Measured at 96 Hrs After Intervention Started. | 96 hours after intervention started | Calculated as serum sodium levels at day one of intervention minus serum sodium levels at 96 hrs after intervention started. |
| Change in Serum Potassium Levels Measured at Day One of Intervention From Serum Potassium Levels Measured at 96 Hrs After Intervention Started. | 96 hours after intervention started | Calculated as serum potassium levels at day one of intervention minus serum potassium levels at 96 hrs after intervention started. |
| Change in Serum Chloride Levels Measured at Day One of Intervention From Serum Chloride Levels Measured at 96 Hrs After Intervention Started. | 96 hours after intervention started | Calculated as serum chloride levels at day one of intervention minus serum chloride levels at 96 hrs after intervention started. |
| Change in Serum Magnesium Levels Measured at Day One of Intervention From Serum Magnesium Levels Measured at 96 Hrs After Intervention Started. | 96 hours after intervention started | Calculated as serum magnesium levels at day one of intervention minus serum magnesium levels at 96 hrs after intervention started. |
| Change in Serum Calcium Levels Measured at Day One of Intervention From Serum Calcium Levels Measured at 96 Hrs After Intervention Started. | 96 hours after intervention started | Calculated as serum calcium levels at day one of intervention minus serum calcium levels at 96 hrs after intervention started. |
Countries
Mexico
Participant flow
Recruitment details
We screened all consecutive patients admitted for acute decompensated heart failure (ADHF) and acute kidney injury (AKI) who were evaluated by the Nephrology service at the Hospital Civil de Guadalajara Fray Antonio Alcalde, an University Hospital, from July 2017 to February 2020.
Pre-assignment details
Of 168 patients assessed for eligibility, 80 met inclusion criteria and were randomized to treatment
Participants by arm
| Arm | Count |
|---|---|
| Stepped Furosemide Furosemide 80 mg every 24 hrs (morning) intravenously every 24 hrs for 4 consecutive days, additionally:
* Day 1 furosemide 100mg / day infused with 100cc of Hartmann solution
* Day 2 Furosemide 200mg / day infused with 100cc of Hartmann solution
* Day 3 Furosemide 300mg / day infused with 100cc of Hartmann solution
* Day 4 Furosemide 400mg / day infused with 100cc of Hartmann solution | 40 |
| Diuretics Combined Furosemide 80 mg every 24 hrs (morning) intravenously every 24 hrs for 4 consecutive days, additionally:
* Day 1 furosemide 100mg / day infused with 100cc of Hartmann solution + Chlortalidone 50mg VO every 24 hours + Spironolactone 50mg VO every 24 hrs.
* Day 2 furosemide 100mg / day infused with 100cc of Hartmann solution + Chlortalidone 50mg VO every 24 hours + Spironolactone 50mg VO every 24 hrs.
* Day 3 furosemide 100mg / day infused with 100cc of Hartmann solution + Chlortalidone 50mg VO every 24 hours + Spironolactone 50mg VO every 24 hrs.
* Day 4 furosemide 100mg / day infused with 100cc of Hartmann solution + Chlortalidone 50mg VO every 24 hours + Spironolactone 50mg VO every 24 hrs. | 40 |
| Total | 80 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| First 4 Days of Intervention | Early improvement | 5 | 7 |
Baseline characteristics
| Characteristic | Total | Stepped Furosemide | Diuretics Combined |
|---|---|---|---|
| 24 hr urinary volume before intervention | 1266.57 ml/day | 1278.93 ml/day | 1235.38 ml/day |
| Acute myocardial infarction | 16 Participants | 8 Participants | 8 Participants |
| Admission to cardiology service | 28 Participants | 14 Participants | 14 Participants |
| Admission to intensive care unit | 1 Participants | 0 Participants | 1 Participants |
| Admission to internal medicine service | 47 Participants | 24 Participants | 23 Participants |
| Admission to other hospital service | 2 Participants | 1 Participants | 1 Participants |
| Admission to surgical service | 2 Participants | 1 Participants | 1 Participants |
| Age, Continuous | 59 years STANDARD_DEVIATION 14.5 | 58 years STANDARD_DEVIATION 14.5 | 59 years STANDARD_DEVIATION 14.6 |
| Arrythmia | 11 Participants | 5 Participants | 6 Participants |
| Baseline estimated glomerular filtration rate | 28 ml/min/1.73m^2 | 31 ml/min/1.73m^2 | 28 ml/min/1.73m^2 |
| Baseline serum creatinine | 2.9 mg/dl | 3.1 mg/dl | 2.8 mg/dl |
| Blood transfusion during hospitalisation | 4 Participants | 3 Participants | 1 Participants |
| Chronic heart failure | 50 Participants | 26 Participants | 24 Participants |
| Chronic kidney disease | 34 Participants | 16 Participants | 18 Participants |
| Current smoker | 36 Participants | 16 Participants | 20 Participants |
| Diabetes | 55 Participants | 25 Participants | 30 Participants |
| Diastolic blood pressure | 75 mmHg STANDARD_DEVIATION 13 | 74 mmHg STANDARD_DEVIATION 12 | 77 mmHg STANDARD_DEVIATION 14 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 80 Participants | 40 Participants | 40 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Heart rate | 85 beats per minute | 87 beats per minute | 82 beats per minute |
| Hypertension | 64 Participants | 29 Participants | 35 Participants |
| Hypothyroidism | 8 Participants | 6 Participants | 2 Participants |
| Oxygen saturation | 94 percentage | 95 percentage | 94 percentage |
| Presence of hematuria in dipstick urinalysis | 34 Participants | 19 Participants | 15 Participants |
| Presence of proteinuria in dipstick urinalysis | 38 Participants | 20 Participants | 18 Participants |
| Previous use of diuretics | 16 Participants | 10 Participants | 6 Participants |
| Serum brain natriuretic peptide | 2631 ng/dl STANDARD_DEVIATION 1713 | 2501 ng/dl STANDARD_DEVIATION 1669 | 2718 ng/dl STANDARD_DEVIATION 1836 |
| Serum copeptin | 75 ng/dl | 75 ng/dl | 72 ng/dl |
| Sex: Female, Male Female | 43 Participants | 21 Participants | 22 Participants |
| Sex: Female, Male Male | 37 Participants | 19 Participants | 18 Participants |
| Systolic blood pressure | 130 mmHg STANDARD_DEVIATION 23 | 126 mmHg STANDARD_DEVIATION 23 | 134 mmHg STANDARD_DEVIATION 22 |
| Uric acid | 8.6 mg/dl | 8.5 mg/dl | 9.1 mg/dl |
| Use of antibiotics at admission | 49 Participants | 23 Participants | 26 Participants |
| Use of Hartmann solution as reanimation fluid | 56 Participants | 27 Participants | 29 Participants |
| Use of inotropic drugs | 2 Participants | 1 Participants | 1 Participants |
| Use of normal saline as reanimation fluid | 4 Participants | 2 Participants | 2 Participants |
| Use of vasopressor drugs | 5 Participants | 3 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 13 / 40 | 16 / 40 |
| other Total, other adverse events | 36 / 40 | 35 / 40 |
| serious Total, serious adverse events | 4 / 40 | 1 / 40 |
Outcome results
Primary
Number of Participants With Renal Function Recovery Defined as a Return to Individual Baseline Serum Creatinine Values
Comparing patient's baseline serum creatinine (previous serum creatinine of 3 months ago and up to a year ago) with creatinine measurements every 24 hours during intervention (4 days)
Time frame: Up to 96 hours after intervention started
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Stepped Furosemide | Number of Participants With Renal Function Recovery Defined as a Return to Individual Baseline Serum Creatinine Values | 8 Participants |
| Diuretics Combined | Number of Participants With Renal Function Recovery Defined as a Return to Individual Baseline Serum Creatinine Values | 5 Participants |
Secondary
An Elevation of at Least 0.3 mg/dl of Serum Creatinine From Day One of Intervention Compared With Serum Creatinine at 96hrs After Intervention Started
Time frame: 96 hours after intervention started
Population: Patients without serum creatinine measured at 96hrs were excluded from this analysis.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Stepped Furosemide | An Elevation of at Least 0.3 mg/dl of Serum Creatinine From Day One of Intervention Compared With Serum Creatinine at 96hrs After Intervention Started | 20 Participants |
| Diuretics Combined | An Elevation of at Least 0.3 mg/dl of Serum Creatinine From Day One of Intervention Compared With Serum Creatinine at 96hrs After Intervention Started | 24 Participants |
Secondary
Change in 24 Hour Urine Output at 96 Hours After Intervention Started From 24 Hour Urine Output One Day Before Intervention Initiation)
Urine output was collected through an urinary catheter and measured and registered by a nurse. The sum of these registrations from 7 am from one day to 7 am of the next day was considered the 24 hour urinary output
Time frame: 96 hours after intervention started
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Stepped Furosemide | Change in 24 Hour Urine Output at 96 Hours After Intervention Started From 24 Hour Urine Output One Day Before Intervention Initiation) | 125 ml |
| Diuretics Combined | Change in 24 Hour Urine Output at 96 Hours After Intervention Started From 24 Hour Urine Output One Day Before Intervention Initiation) | 200 ml |
Secondary
Change in Serum Creatinine at Day One of Intervention From Serum Creatinine at 96 Hrs After Intervention Started
Calculated as serum creatinine at day one minus serum creatinine at 96 hrs after intervention started
Time frame: 96 hours after intervention started
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Stepped Furosemide | Change in Serum Creatinine at Day One of Intervention From Serum Creatinine at 96 Hrs After Intervention Started | 0.02 mg/dl |
| Diuretics Combined | Change in Serum Creatinine at Day One of Intervention From Serum Creatinine at 96 Hrs After Intervention Started | 0.2 mg/dl |
Secondary
In Hospital Mortality Defined as Number of Dead Patients From Day One of Intervention and Before Discharge
Time frame: From day one of intervention up to discharge, an average of 1 week
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Stepped Furosemide | In Hospital Mortality Defined as Number of Dead Patients From Day One of Intervention and Before Discharge | 4 Participants |
| Diuretics Combined | In Hospital Mortality Defined as Number of Dead Patients From Day One of Intervention and Before Discharge | 4 Participants |
Secondary
Mortality During Follow up Defined as Number of Dead Patients After Discharge
Time frame: From day one after discharge up to an average of 161 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Stepped Furosemide | Mortality During Follow up Defined as Number of Dead Patients After Discharge | 9 Participants |
| Diuretics Combined | Mortality During Follow up Defined as Number of Dead Patients After Discharge | 12 Participants |
Secondary
Number of Days From the Beginning of the Intervention Until Patients Referred Dyspnea Improvement or a Reduction in Supplementary Oxygen Requirements Was Made.
Dyspnea improvement was referred by the patient as the clinician asked them do you feel more or less difficult to breathe? or if the liters per minute or the fraction of inspired supplementary oxygen necessary maintain an oxygen saturation \>90% were diminished
Time frame: Up to 4 days after intervention started
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Stepped Furosemide | Number of Days From the Beginning of the Intervention Until Patients Referred Dyspnea Improvement or a Reduction in Supplementary Oxygen Requirements Was Made. | 4 days |
| Diuretics Combined | Number of Days From the Beginning of the Intervention Until Patients Referred Dyspnea Improvement or a Reduction in Supplementary Oxygen Requirements Was Made. | 4 days |
Secondary
Number of Patients That Required Renal Replacement Therapy of Any Type During Intervention (4 Days).
The requirement of renal replacement therapy was assessed by the nephrology team in charge
Time frame: Up to 96 hours after intervention started
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Stepped Furosemide | Number of Patients That Required Renal Replacement Therapy of Any Type During Intervention (4 Days). | 7 Participants |
| Diuretics Combined | Number of Patients That Required Renal Replacement Therapy of Any Type During Intervention (4 Days). | 6 Participants |
Secondary
Number of Patients With Dyspnea Improvement as Referred by the Patient or Reduction in Supplementary Oxygen Requirements at 96 Hours After Intervention Started
Dyspnea improvement was referred by the patient as the clinician asked them do you feel more or less difficult to breathe? or if the liters per minute or the fraction of inspired supplementary oxygen necessary to maintain an oxygen saturation \>90% were diminished
Time frame: Up to 96 hours after intervention started
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Stepped Furosemide | Number of Patients With Dyspnea Improvement as Referred by the Patient or Reduction in Supplementary Oxygen Requirements at 96 Hours After Intervention Started | 27 Participants |
| Diuretics Combined | Number of Patients With Dyspnea Improvement as Referred by the Patient or Reduction in Supplementary Oxygen Requirements at 96 Hours After Intervention Started | 27 Participants |
Secondary
Number of Patients With Dyspnea Improvement as Referred by the Patient or Reduction in Supplementary Oxygen Requirements Before Day 3 of Intervention
Dyspnea improvement was referred by the patient as the clinician asked them do you feel more or less difficult to breathe? or if the liters per minute or the fraction of inspired supplementary oxygen necessary maintain an oxygen saturation \>90% were diminished
Time frame: Up to 3 days after intervention started
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Stepped Furosemide | Number of Patients With Dyspnea Improvement as Referred by the Patient or Reduction in Supplementary Oxygen Requirements Before Day 3 of Intervention | 2 Participants |
| Diuretics Combined | Number of Patients With Dyspnea Improvement as Referred by the Patient or Reduction in Supplementary Oxygen Requirements Before Day 3 of Intervention | 7 Participants |
Other Pre-specified
Change in Serum Bicarbonate Levels Measured at Day One of Intervention From Serum Bicarbonate Levels Measured at 96 Hrs After Intervention Started.
Calculated as serum bicarbonate levels at day one of intervention minus bicarbonate levels at 96 hrs after intervention started.
Time frame: 96 hours after intervention started
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Stepped Furosemide | Change in Serum Bicarbonate Levels Measured at Day One of Intervention From Serum Bicarbonate Levels Measured at 96 Hrs After Intervention Started. | 2.9 mEq/L |
| Diuretics Combined | Change in Serum Bicarbonate Levels Measured at Day One of Intervention From Serum Bicarbonate Levels Measured at 96 Hrs After Intervention Started. | 3 mEq/L |
Other Pre-specified
Change in Serum Brain Natriuretic Peptide Levels at Baseline From Serum Brain Natriuretic Peptide Levels at 96 Hours After Intervention Started
Baseline levels were defined as the measurement at hospital admission. Calculated as serum brain natriuretic peptide levels at baseline minus serum brain natriuretic peptide levels at 96 hours after intervention started
Time frame: 96 hours after intervention started
Population: Patients without baseline brain natriuretic peptide measurements and/or without measurements at 96hrs were excluded from this analysis
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Stepped Furosemide | Change in Serum Brain Natriuretic Peptide Levels at Baseline From Serum Brain Natriuretic Peptide Levels at 96 Hours After Intervention Started | -1344 ng/dl | Standard Deviation 1041 |
| Diuretics Combined | Change in Serum Brain Natriuretic Peptide Levels at Baseline From Serum Brain Natriuretic Peptide Levels at 96 Hours After Intervention Started | -1378 ng/dl | Standard Deviation 1904 |
Other Pre-specified
Change in Serum Calcium Levels Measured at Day One of Intervention From Serum Calcium Levels Measured at 96 Hrs After Intervention Started.
Calculated as serum calcium levels at day one of intervention minus serum calcium levels at 96 hrs after intervention started.
Time frame: 96 hours after intervention started
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Stepped Furosemide | Change in Serum Calcium Levels Measured at Day One of Intervention From Serum Calcium Levels Measured at 96 Hrs After Intervention Started. | 0.15 mg/dl |
| Diuretics Combined | Change in Serum Calcium Levels Measured at Day One of Intervention From Serum Calcium Levels Measured at 96 Hrs After Intervention Started. | -0.05 mg/dl |
Other Pre-specified
Change in Serum Chloride Levels Measured at Day One of Intervention From Serum Chloride Levels Measured at 96 Hrs After Intervention Started.
Calculated as serum chloride levels at day one of intervention minus serum chloride levels at 96 hrs after intervention started.
Time frame: 96 hours after intervention started
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Stepped Furosemide | Change in Serum Chloride Levels Measured at Day One of Intervention From Serum Chloride Levels Measured at 96 Hrs After Intervention Started. | -0.6 mEq/L | Standard Deviation 6.4 |
| Diuretics Combined | Change in Serum Chloride Levels Measured at Day One of Intervention From Serum Chloride Levels Measured at 96 Hrs After Intervention Started. | -0.4 mEq/L | Standard Deviation 4.7 |
Other Pre-specified
Change in Serum Copeptin Levels at Day One of Intervention From Serum Copeptin Levels Measured at 96 Hrs After Intervention Started.
Calculated as serum copeptin levels at day one minus serum copeptin levels measured at 96 hrs after intervention started
Time frame: 96 hours after intervention started
Population: Patients without the copeptin measurements made at day one and/or at 96hrs were excluded from this analysis
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Stepped Furosemide | Change in Serum Copeptin Levels at Day One of Intervention From Serum Copeptin Levels Measured at 96 Hrs After Intervention Started. | 1.1 ng/dl |
| Diuretics Combined | Change in Serum Copeptin Levels at Day One of Intervention From Serum Copeptin Levels Measured at 96 Hrs After Intervention Started. | -16 ng/dl |
Other Pre-specified
Change in Serum Lactate Levels Measured at Day One of Intervention From Serum Lactate Levels Measured at 96 Hrs After Intervention Started.
Calculated as serum lactate levels at day one of intervention minus serum lactate levels at 96 hrs after intervention started.
Time frame: 96 hours after intervention started
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Stepped Furosemide | Change in Serum Lactate Levels Measured at Day One of Intervention From Serum Lactate Levels Measured at 96 Hrs After Intervention Started. | 0 mmol/L |
| Diuretics Combined | Change in Serum Lactate Levels Measured at Day One of Intervention From Serum Lactate Levels Measured at 96 Hrs After Intervention Started. | 0.1 mmol/L |
Other Pre-specified
Change in Serum Magnesium Levels Measured at Day One of Intervention From Serum Magnesium Levels Measured at 96 Hrs After Intervention Started.
Calculated as serum magnesium levels at day one of intervention minus serum magnesium levels at 96 hrs after intervention started.
Time frame: 96 hours after intervention started
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Stepped Furosemide | Change in Serum Magnesium Levels Measured at Day One of Intervention From Serum Magnesium Levels Measured at 96 Hrs After Intervention Started. | 0.07 mg/dl | Standard Deviation 0.16 |
| Diuretics Combined | Change in Serum Magnesium Levels Measured at Day One of Intervention From Serum Magnesium Levels Measured at 96 Hrs After Intervention Started. | -0.04 mg/dl | Standard Deviation 0.2 |
Other Pre-specified
Change in Serum Partial Pressure of Carbon Dioxide Measured at Day One of Intervention From Serum Partial Pressure of Carbon Dioxide Measured at 96 Hrs After Intervention Started.
Calculated as serum partial pressure of carbon dioxide at day one of intervention minus serum partial pressure of carbon dioxide at 96 hrs after intervention started.
Time frame: 96 hours after intervention started
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Stepped Furosemide | Change in Serum Partial Pressure of Carbon Dioxide Measured at Day One of Intervention From Serum Partial Pressure of Carbon Dioxide Measured at 96 Hrs After Intervention Started. | 1 mmHg |
| Diuretics Combined | Change in Serum Partial Pressure of Carbon Dioxide Measured at Day One of Intervention From Serum Partial Pressure of Carbon Dioxide Measured at 96 Hrs After Intervention Started. | 3 mmHg |
Other Pre-specified
Change in Serum pH Value Measured at Day One of Intervention From Serum pH Value Measured at 96 Hrs After Intervention Started.
Calculated as serum pH value at day one of intervention minus serum pH value at 96 hrs after intervention started.
Time frame: 96 hours after intervention started
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Stepped Furosemide | Change in Serum pH Value Measured at Day One of Intervention From Serum pH Value Measured at 96 Hrs After Intervention Started. | 0.03 units | Standard Deviation 0.07 |
| Diuretics Combined | Change in Serum pH Value Measured at Day One of Intervention From Serum pH Value Measured at 96 Hrs After Intervention Started. | 0.02 units | Standard Deviation 0.04 |
Other Pre-specified
Change in Serum Potassium Levels Measured at Day One of Intervention From Serum Potassium Levels Measured at 96 Hrs After Intervention Started.
Calculated as serum potassium levels at day one of intervention minus serum potassium levels at 96 hrs after intervention started.
Time frame: 96 hours after intervention started
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Stepped Furosemide | Change in Serum Potassium Levels Measured at Day One of Intervention From Serum Potassium Levels Measured at 96 Hrs After Intervention Started. | -0.2 mEq/L | Standard Deviation 0.9 |
| Diuretics Combined | Change in Serum Potassium Levels Measured at Day One of Intervention From Serum Potassium Levels Measured at 96 Hrs After Intervention Started. | -0.4 mEq/L | Standard Deviation 0.8 |
Other Pre-specified
Change in Serum Sodium Levels Measured at Day One of Intervention From Serum Sodium Levels Measured at 96 Hrs After Intervention Started.
Calculated as serum sodium levels at day one of intervention minus serum sodium levels at 96 hrs after intervention started.
Time frame: 96 hours after intervention started
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Stepped Furosemide | Change in Serum Sodium Levels Measured at Day One of Intervention From Serum Sodium Levels Measured at 96 Hrs After Intervention Started. | -1.2 mEq/L | Standard Deviation 4.7 |
| Diuretics Combined | Change in Serum Sodium Levels Measured at Day One of Intervention From Serum Sodium Levels Measured at 96 Hrs After Intervention Started. | 0.2 mEq/L | Standard Deviation 4.7 |
Other Pre-specified
Change in Serum Urea Levels Measured at Day One of Intervention From Serum Urea Levels Measured at 96 Hrs After Intervention Started.
Calculated as serum urea levels at day one of intervention minus serum urea levels at 96 hrs after intervention started.
Time frame: 96 hours after intervention started
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Stepped Furosemide | Change in Serum Urea Levels Measured at Day One of Intervention From Serum Urea Levels Measured at 96 Hrs After Intervention Started. | 13 mg/dl |
| Diuretics Combined | Change in Serum Urea Levels Measured at Day One of Intervention From Serum Urea Levels Measured at 96 Hrs After Intervention Started. | 18 mg/dl |
Other Pre-specified
Number of Patients That Achieved >30% Reduction in Brain Natriuretic Compared With Baseline Levels
Baseline levels were defined as the measurement at hospital admission
Time frame: Up to 96 hours after intervention started
Population: Patients without baseline brain natriuretic peptide measurements and/or without measurements at 96hrs were excluded from this analysis
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Stepped Furosemide | Number of Patients That Achieved >30% Reduction in Brain Natriuretic Compared With Baseline Levels | 5 Participants |
| Diuretics Combined | Number of Patients That Achieved >30% Reduction in Brain Natriuretic Compared With Baseline Levels | 7 Participants |
Other Pre-specified
Number of Patients Whose Interventions Were Stopped Because Clinical Improvement Was Achieved Before 96 Hours as Assessed by de Clinical Judgement of the Medical Team in Charge.
Clinical improvement was referred as remission of symptoms with achievement of 24 hour urine output equal or greater than 3000 milliliters
Time frame: From the beginning of intervention and before 96 hours after that
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Stepped Furosemide | Number of Patients Whose Interventions Were Stopped Because Clinical Improvement Was Achieved Before 96 Hours as Assessed by de Clinical Judgement of the Medical Team in Charge. | 5 Participants |
| Diuretics Combined | Number of Patients Whose Interventions Were Stopped Because Clinical Improvement Was Achieved Before 96 Hours as Assessed by de Clinical Judgement of the Medical Team in Charge. | 7 Participants |