Trial Outcomes & Findings for The Effect in Renal Function on Patients With Type 1 Cardiorenal Syndrome Treated With Two Strategies of Furosemide. (NCT NCT04393493)

NCT ID: NCT04393493

Last Updated: 2020-09-14

Results Overview

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)

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 80 participants
• Primary outcome timeframe: Up to 96 hours after intervention started
• Results posted on: 2020-09-14

Participant Flow

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.

Of 168 patients assessed for eligibility, 80 met inclusion criteria and were randomized to treatment

Participant milestones

Measure	Stepped Furosemide Furosemide 80 mg every 24 hrs (morning) intravenously every 24 hrs for 4 consecutive days, additionally continuous infused furosemide as follows: * 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	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 orally every 24 hours + Spironolactone 25mg orally every 24 hrs. * Day 2 furosemide 100mg / day infused with 100cc of Hartmann solution + Chlortalidone 50mg orally every 24 hours + Spironolactone 25mg orally every 24 hrs. * Day 3 furosemide 100mg / day infused with 100cc of Hartmann solution + Chlortalidone 50mg orally every 24 hours + Spironolactone 25mg orally every 24 hrs. * Day 4 furosemide 100mg / day infused with 100cc of Hartmann solution + Chlortalidone 50mg orally every 24 hours + Spironolactone 25mg orally every 24 hrs.
Follow up STARTED	40	40
Follow up COMPLETED	40	40
Follow up NOT COMPLETED	0	0
First 4 Days of Intervention STARTED	40	40
First 4 Days of Intervention COMPLETED	35	33
First 4 Days of Intervention NOT COMPLETED	5	7

Reasons for withdrawal

Measure	Stepped Furosemide Furosemide 80 mg every 24 hrs (morning) intravenously every 24 hrs for 4 consecutive days, additionally continuous infused furosemide as follows: * 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	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 orally every 24 hours + Spironolactone 25mg orally every 24 hrs. * Day 2 furosemide 100mg / day infused with 100cc of Hartmann solution + Chlortalidone 50mg orally every 24 hours + Spironolactone 25mg orally every 24 hrs. * Day 3 furosemide 100mg / day infused with 100cc of Hartmann solution + Chlortalidone 50mg orally every 24 hours + Spironolactone 25mg orally every 24 hrs. * Day 4 furosemide 100mg / day infused with 100cc of Hartmann solution + Chlortalidone 50mg orally every 24 hours + Spironolactone 25mg orally every 24 hrs.
First 4 Days of Intervention Early improvement	5	7

Baseline Characteristics

Patients without the information required to assess this variable where excluded from the calculation

Baseline characteristics by cohort

Measure	Stepped Furosemide n=40 Participants 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	Diuretics Combined n=40 Participants 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.	Total n=80 Participants Total of all reporting groups
Age, Continuous	58 years STANDARD_DEVIATION 14.5 • n=40 Participants	59 years STANDARD_DEVIATION 14.6 • n=40 Participants	59 years STANDARD_DEVIATION 14.5 • n=80 Participants
Sex: Female, Male Female	21 Participants n=40 Participants	22 Participants n=40 Participants	43 Participants n=80 Participants
Sex: Female, Male Male	19 Participants n=40 Participants	18 Participants n=40 Participants	37 Participants n=80 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	40 Participants n=40 Participants	40 Participants n=40 Participants	80 Participants n=80 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	0 Participants n=40 Participants	0 Participants n=40 Participants	0 Participants n=80 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=40 Participants	0 Participants n=40 Participants	0 Participants n=80 Participants
Diabetes	25 Participants n=39 Participants • Patients without the information required to assess this variable where excluded from the calculation	30 Participants n=38 Participants • Patients without the information required to assess this variable where excluded from the calculation	55 Participants n=77 Participants • Patients without the information required to assess this variable where excluded from the calculation
Hypertension	29 Participants n=39 Participants • Patients without the information required to assess this variable where excluded from the calculation	35 Participants n=38 Participants • Patients without the information required to assess this variable where excluded from the calculation	64 Participants n=77 Participants • Patients without the information required to assess this variable where excluded from the calculation
Baseline serum creatinine	3.1 mg/dl n=40 Participants	2.8 mg/dl n=40 Participants	2.9 mg/dl n=80 Participants
Chronic kidney disease	16 Participants n=39 Participants • Patients without the information required to assess this variable where excluded from the calculation	18 Participants n=38 Participants • Patients without the information required to assess this variable where excluded from the calculation	34 Participants n=77 Participants • Patients without the information required to assess this variable where excluded from the calculation
Baseline estimated glomerular filtration rate	31 ml/min/1.73m^2 n=40 Participants	28 ml/min/1.73m^2 n=40 Participants	28 ml/min/1.73m^2 n=80 Participants
Acute myocardial infarction	8 Participants n=38 Participants • Patients without the information required to assess this variable where excluded from the calculation	8 Participants n=37 Participants • Patients without the information required to assess this variable where excluded from the calculation	16 Participants n=75 Participants • Patients without the information required to assess this variable where excluded from the calculation
Chronic heart failure	26 Participants n=39 Participants • Patients without the information required to assess this variable where excluded from the calculation	24 Participants n=37 Participants • Patients without the information required to assess this variable where excluded from the calculation	50 Participants n=76 Participants • Patients without the information required to assess this variable where excluded from the calculation
Hypothyroidism	6 Participants n=37 Participants • Patients without the information required to assess this variable where excluded from the calculation	2 Participants n=38 Participants • Patients without the information required to assess this variable where excluded from the calculation	8 Participants n=75 Participants • Patients without the information required to assess this variable where excluded from the calculation
Arrythmia	5 Participants n=39 Participants • Patients without the information required to assess this variable where excluded from the calculation	6 Participants n=38 Participants • Patients without the information required to assess this variable where excluded from the calculation	11 Participants n=77 Participants • Patients without the information required to assess this variable where excluded from the calculation
Current smoker	16 Participants n=39 Participants • Patients without the information required to assess this variable where excluded from the calculation	20 Participants n=38 Participants • Patients without the information required to assess this variable where excluded from the calculation	36 Participants n=77 Participants • Patients without the information required to assess this variable where excluded from the calculation
Heart rate	87 beats per minute n=40 Participants	82 beats per minute n=40 Participants	85 beats per minute n=80 Participants
Oxygen saturation	95 percentage n=40 Participants	94 percentage n=40 Participants	94 percentage n=80 Participants
Systolic blood pressure	126 mmHg STANDARD_DEVIATION 23 • n=40 Participants	134 mmHg STANDARD_DEVIATION 22 • n=40 Participants	130 mmHg STANDARD_DEVIATION 23 • n=80 Participants
Diastolic blood pressure	74 mmHg STANDARD_DEVIATION 12 • n=40 Participants	77 mmHg STANDARD_DEVIATION 14 • n=40 Participants	75 mmHg STANDARD_DEVIATION 13 • n=80 Participants
Uric acid	8.5 mg/dl n=17 Participants • Patients without the information required to assess this variable where excluded from the calculation	9.1 mg/dl n=14 Participants • Patients without the information required to assess this variable where excluded from the calculation	8.6 mg/dl n=31 Participants • Patients without the information required to assess this variable where excluded from the calculation
Presence of proteinuria in dipstick urinalysis	20 Participants n=30 Participants • Patients without the information required to assess this variable where excluded from the calculation	18 Participants n=29 Participants • Patients without the information required to assess this variable where excluded from the calculation	38 Participants n=59 Participants • Patients without the information required to assess this variable where excluded from the calculation
Presence of hematuria in dipstick urinalysis	19 Participants n=30 Participants • Patients without the information required to assess this variable where excluded from the calculation	15 Participants n=29 Participants • Patients without the information required to assess this variable where excluded from the calculation	34 Participants n=59 Participants • Patients without the information required to assess this variable where excluded from the calculation
Serum brain natriuretic peptide	2501 ng/dl STANDARD_DEVIATION 1669 • n=11 Participants • Patients without the information required to assess this variable where excluded from the calculation	2718 ng/dl STANDARD_DEVIATION 1836 • n=13 Participants • Patients without the information required to assess this variable where excluded from the calculation	2631 ng/dl STANDARD_DEVIATION 1713 • n=24 Participants • Patients without the information required to assess this variable where excluded from the calculation
Serum copeptin	75 ng/dl n=18 Participants • Patients without the information required to assess this variable where excluded from the calculation	72 ng/dl n=17 Participants • Patients without the information required to assess this variable where excluded from the calculation	75 ng/dl n=35 Participants • Patients without the information required to assess this variable where excluded from the calculation
Use of antibiotics at admission	23 Participants n=38 Participants • Patients without the information required to assess this variable where excluded from the calculation	26 Participants n=37 Participants • Patients without the information required to assess this variable where excluded from the calculation	49 Participants n=75 Participants • Patients without the information required to assess this variable where excluded from the calculation
Blood transfusion during hospitalisation	3 Participants n=37 Participants • Patients without the information required to assess this variable where excluded from the calculation	1 Participants n=37 Participants • Patients without the information required to assess this variable where excluded from the calculation	4 Participants n=74 Participants • Patients without the information required to assess this variable where excluded from the calculation
Use of vasopressor drugs	3 Participants n=37 Participants • Patients without the information required to assess this variable where excluded from the calculation	2 Participants n=37 Participants • Patients without the information required to assess this variable where excluded from the calculation	5 Participants n=74 Participants • Patients without the information required to assess this variable where excluded from the calculation
Use of inotropic drugs	1 Participants n=37 Participants • Patients without the information required to assess this variable where excluded from the calculation	1 Participants n=37 Participants • Patients without the information required to assess this variable where excluded from the calculation	2 Participants n=74 Participants • Patients without the information required to assess this variable where excluded from the calculation
24 hr urinary volume before intervention	1278.93 ml/day n=40 Participants	1235.38 ml/day n=40 Participants	1266.57 ml/day n=80 Participants
Use of normal saline as reanimation fluid	2 Participants n=40 Participants	2 Participants n=40 Participants	4 Participants n=80 Participants
Use of Hartmann solution as reanimation fluid	27 Participants n=40 Participants • Patients without the information required to assess this variable where excluded from the calculation	29 Participants n=39 Participants • Patients without the information required to assess this variable where excluded from the calculation	56 Participants n=79 Participants • Patients without the information required to assess this variable where excluded from the calculation
Previous use of diuretics	10 Participants n=40 Participants	6 Participants n=40 Participants	16 Participants n=80 Participants
Admission to internal medicine service	24 Participants n=40 Participants	23 Participants n=40 Participants	47 Participants n=80 Participants
Admission to cardiology service	14 Participants n=40 Participants	14 Participants n=40 Participants	28 Participants n=80 Participants
Admission to intensive care unit	0 Participants n=40 Participants	1 Participants n=40 Participants	1 Participants n=80 Participants
Admission to surgical service	1 Participants n=40 Participants	1 Participants n=40 Participants	2 Participants n=80 Participants
Admission to other hospital service	1 Participants n=40 Participants	1 Participants n=40 Participants	2 Participants n=80 Participants

PRIMARY outcome

Timeframe: 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)

Outcome measures

Measure	Diuretics Combined n=40 Participants 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.	Stepped Furosemide n=40 Participants Furosemide 80 mg every 24 hrs (morning) intravenously every 24 hrs for 4 consecutive days, additionally continuous infused furosemide as follows: * 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
Number of Participants With Renal Function Recovery Defined as a Return to Individual Baseline Serum Creatinine Values	5 Participants	8 Participants

SECONDARY outcome

Timeframe: 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

Outcome measures

Measure	Diuretics Combined n=40 Participants 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.	Stepped Furosemide n=40 Participants Furosemide 80 mg every 24 hrs (morning) intravenously every 24 hrs for 4 consecutive days, additionally continuous infused furosemide as follows: * 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
Change in 24 Hour Urine Output at 96 Hours After Intervention Started From 24 Hour Urine Output One Day Before Intervention Initiation)	200 ml Interval -625.0 to 363.0	125 ml Interval -350.0 to 1312.0

SECONDARY outcome

Timeframe: 96 hours after intervention started

Calculated as serum creatinine at day one minus serum creatinine at 96 hrs after intervention started

Outcome measures

Measure	Diuretics Combined n=40 Participants 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.	Stepped Furosemide n=40 Participants Furosemide 80 mg every 24 hrs (morning) intravenously every 24 hrs for 4 consecutive days, additionally continuous infused furosemide as follows: * 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
Change in Serum Creatinine at Day One of Intervention From Serum Creatinine at 96 Hrs After Intervention Started	0.2 mg/dl Interval -0.02 to 0.5	0.02 mg/dl Interval -0.3 to 0.6

SECONDARY outcome

Timeframe: 96 hours after intervention started

Population: Patients without serum creatinine measured at 96hrs were excluded from this analysis.

Outcome measures

Measure	Diuretics Combined n=35 Participants 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.	Stepped Furosemide n=37 Participants Furosemide 80 mg every 24 hrs (morning) intravenously every 24 hrs for 4 consecutive days, additionally continuous infused furosemide as follows: * 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
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	20 Participants

SECONDARY outcome

Timeframe: From day one of intervention up to discharge, an average of 1 week

Outcome measures

Measure	Diuretics Combined n=40 Participants 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.	Stepped Furosemide n=40 Participants Furosemide 80 mg every 24 hrs (morning) intravenously every 24 hrs for 4 consecutive days, additionally continuous infused furosemide as follows: * 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
In Hospital Mortality Defined as Number of Dead Patients From Day One of Intervention and Before Discharge	4 Participants	4 Participants

SECONDARY outcome

Timeframe: From day one after discharge up to an average of 161 days

Outcome measures

Measure	Diuretics Combined n=36 Participants 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.	Stepped Furosemide n=36 Participants Furosemide 80 mg every 24 hrs (morning) intravenously every 24 hrs for 4 consecutive days, additionally continuous infused furosemide as follows: * 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
Mortality During Follow up Defined as Number of Dead Patients After Discharge	12 Participants	9 Participants

SECONDARY outcome

Timeframe: 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

Outcome measures

Measure	Diuretics Combined n=40 Participants 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.	Stepped Furosemide n=40 Participants Furosemide 80 mg every 24 hrs (morning) intravenously every 24 hrs for 4 consecutive days, additionally continuous infused furosemide as follows: * 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
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	27 Participants

SECONDARY outcome

Timeframe: 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

Outcome measures

Measure	Diuretics Combined n=40 Participants 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.	Stepped Furosemide n=40 Participants Furosemide 80 mg every 24 hrs (morning) intravenously every 24 hrs for 4 consecutive days, additionally continuous infused furosemide as follows: * 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
Number of Patients With Dyspnea Improvement as Referred by the Patient or Reduction in Supplementary Oxygen Requirements Before Day 3 of Intervention	7 Participants	2 Participants

SECONDARY outcome

Timeframe: 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

Outcome measures

Measure	Diuretics Combined n=40 Participants 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.	Stepped Furosemide n=40 Participants Furosemide 80 mg every 24 hrs (morning) intravenously every 24 hrs for 4 consecutive days, additionally continuous infused furosemide as follows: * 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
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 Interval 2.2 to 4.0	4 days Interval 3.0 to 4.0

SECONDARY outcome

Timeframe: Up to 96 hours after intervention started

The requirement of renal replacement therapy was assessed by the nephrology team in charge

Outcome measures

Measure	Diuretics Combined n=38 Participants 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.	Stepped Furosemide n=38 Participants Furosemide 80 mg every 24 hrs (morning) intravenously every 24 hrs for 4 consecutive days, additionally continuous infused furosemide as follows: * 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
Number of Patients That Required Renal Replacement Therapy of Any Type During Intervention (4 Days).	6 Participants	7 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: 96 hours after intervention started

Population: Patients without the copeptin measurements made at day one and/or at 96hrs were excluded from this analysis

Calculated as serum copeptin levels at day one minus serum copeptin levels measured at 96 hrs after intervention started

Outcome measures

Measure	Diuretics Combined n=23 Participants 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.	Stepped Furosemide n=22 Participants Furosemide 80 mg every 24 hrs (morning) intravenously every 24 hrs for 4 consecutive days, additionally continuous infused furosemide as follows: * 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
Change in Serum Copeptin Levels at Day One of Intervention From Serum Copeptin Levels Measured at 96 Hrs After Intervention Started.	-16 ng/dl Interval -26.0 to 13.0	1.1 ng/dl Interval -20.0 to 21.0

OTHER_PRE_SPECIFIED outcome

Timeframe: 96 hours after intervention started

Population: Patients without baseline brain natriuretic peptide measurements and/or without measurements at 96hrs were excluded from this analysis

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

Outcome measures

Measure	Diuretics Combined n=9 Participants 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.	Stepped Furosemide n=7 Participants Furosemide 80 mg every 24 hrs (morning) intravenously every 24 hrs for 4 consecutive days, additionally continuous infused furosemide as follows: * 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
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	-1344 ng/dl Standard Deviation 1041

OTHER_PRE_SPECIFIED outcome

Timeframe: 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

Baseline levels were defined as the measurement at hospital admission

Outcome measures

Measure	Diuretics Combined n=9 Participants 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.	Stepped Furosemide n=7 Participants Furosemide 80 mg every 24 hrs (morning) intravenously every 24 hrs for 4 consecutive days, additionally continuous infused furosemide as follows: * 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
Number of Patients That Achieved >30% Reduction in Brain Natriuretic Compared With Baseline Levels	7 Participants	5 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: 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

Outcome measures

Measure	Diuretics Combined n=40 Participants 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.	Stepped Furosemide n=40 Participants Furosemide 80 mg every 24 hrs (morning) intravenously every 24 hrs for 4 consecutive days, additionally continuous infused furosemide as follows: * 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
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	5 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: 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.

Outcome measures

Measure	Diuretics Combined n=40 Participants 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.	Stepped Furosemide n=40 Participants Furosemide 80 mg every 24 hrs (morning) intravenously every 24 hrs for 4 consecutive days, additionally continuous infused furosemide as follows: * 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
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 Interval -1.0 to 45.0	13 mg/dl Interval -11.0 to 37.0

OTHER_PRE_SPECIFIED outcome

Timeframe: 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.

Outcome measures

Measure	Diuretics Combined n=40 Participants 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.	Stepped Furosemide n=40 Participants Furosemide 80 mg every 24 hrs (morning) intravenously every 24 hrs for 4 consecutive days, additionally continuous infused furosemide as follows: * 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
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	-1.2 mEq/L Standard Deviation 4.7

OTHER_PRE_SPECIFIED outcome

Timeframe: 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.

Outcome measures

Measure	Diuretics Combined n=40 Participants 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.	Stepped Furosemide n=40 Participants Furosemide 80 mg every 24 hrs (morning) intravenously every 24 hrs for 4 consecutive days, additionally continuous infused furosemide as follows: * 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
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	-0.2 mEq/L Standard Deviation 0.9

OTHER_PRE_SPECIFIED outcome

Timeframe: 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.

Outcome measures

Measure	Diuretics Combined n=40 Participants 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.	Stepped Furosemide n=40 Participants Furosemide 80 mg every 24 hrs (morning) intravenously every 24 hrs for 4 consecutive days, additionally continuous infused furosemide as follows: * 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
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	-0.6 mEq/L Standard Deviation 6.4

OTHER_PRE_SPECIFIED outcome

Timeframe: 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.

Outcome measures

Measure	Diuretics Combined n=40 Participants 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.	Stepped Furosemide n=40 Participants Furosemide 80 mg every 24 hrs (morning) intravenously every 24 hrs for 4 consecutive days, additionally continuous infused furosemide as follows: * 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
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	0.07 mg/dl Standard Deviation 0.16

OTHER_PRE_SPECIFIED outcome

Timeframe: 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.

Outcome measures

Measure	Diuretics Combined n=40 Participants 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.	Stepped Furosemide n=40 Participants Furosemide 80 mg every 24 hrs (morning) intravenously every 24 hrs for 4 consecutive days, additionally continuous infused furosemide as follows: * 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
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 Interval -0.2 to 0.3	0.15 mg/dl Interval -0.4 to 0.6

OTHER_PRE_SPECIFIED outcome

Timeframe: 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.

Outcome measures

Measure	Diuretics Combined n=40 Participants 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.	Stepped Furosemide n=40 Participants Furosemide 80 mg every 24 hrs (morning) intravenously every 24 hrs for 4 consecutive days, additionally continuous infused furosemide as follows: * 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
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	0.03 units Standard Deviation 0.07

OTHER_PRE_SPECIFIED outcome

Timeframe: 96 hours after intervention started

Calculated as serum bicarbonate levels at day one of intervention minus bicarbonate levels at 96 hrs after intervention started.

Outcome measures

Measure	Diuretics Combined n=40 Participants 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.	Stepped Furosemide n=40 Participants Furosemide 80 mg every 24 hrs (morning) intravenously every 24 hrs for 4 consecutive days, additionally continuous infused furosemide as follows: * 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
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 Interval 1.1 to 4.7	2.9 mEq/L Interval 0.3 to 5.5

OTHER_PRE_SPECIFIED outcome

Timeframe: 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.

Outcome measures

Measure	Diuretics Combined n=40 Participants 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.	Stepped Furosemide n=40 Participants Furosemide 80 mg every 24 hrs (morning) intravenously every 24 hrs for 4 consecutive days, additionally continuous infused furosemide as follows: * 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
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 Interval -1.5 to 6.0	1 mmHg Interval -2.0 to 6.7

OTHER_PRE_SPECIFIED outcome

Timeframe: 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.

Outcome measures

Measure	Diuretics Combined n=40 Participants 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.	Stepped Furosemide n=40 Participants Furosemide 80 mg every 24 hrs (morning) intravenously every 24 hrs for 4 consecutive days, additionally continuous infused furosemide as follows: * 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
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 Interval -0.2 to 0.3	0 mmol/L Interval -0.3 to 0.4

Adverse Events

Stepped Furosemide

Serious events: 4 serious events

Other events: 36 other events

Deaths: 13 deaths

Diuretics Combined

Serious events: 1 serious events

Other events: 35 other events

Deaths: 16 deaths

Serious adverse events

Measure	Stepped Furosemide n=40 participants at risk Furosemide 80 mg every 24 hrs (morning) intravenously every 24 hrs for 4 consecutive days, additionally continuous infused furosemide as follows: * 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	Diuretics Combined n=40 participants at risk 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.
Vascular disorders Hypotension	10.0% 4/40 • Number of events 4 • All-cause mortality was assessed at hospitalisation and during follow-up which lasted an average of 182 days. Serious adverse events and other adverse events were assessed during the 4 days that the intervention lasted. We assessed serious adverse events and other adverse events through daily clinical evaluation by one member of the nephrology team in charge and daily laboratory testing for serum creatinine, urea, glucose, sodium, potassium, chlorine, calcium, phosphorous, arterial or venous blood gas, and complete blood count. All cause mortality during follow-up was assessed through monthly phone calls to patients and/or searching at Hospital electronic records.	2.5% 1/40 • Number of events 1 • All-cause mortality was assessed at hospitalisation and during follow-up which lasted an average of 182 days. Serious adverse events and other adverse events were assessed during the 4 days that the intervention lasted. We assessed serious adverse events and other adverse events through daily clinical evaluation by one member of the nephrology team in charge and daily laboratory testing for serum creatinine, urea, glucose, sodium, potassium, chlorine, calcium, phosphorous, arterial or venous blood gas, and complete blood count. All cause mortality during follow-up was assessed through monthly phone calls to patients and/or searching at Hospital electronic records.

Other adverse events

Measure	Stepped Furosemide n=40 participants at risk Furosemide 80 mg every 24 hrs (morning) intravenously every 24 hrs for 4 consecutive days, additionally continuous infused furosemide as follows: * 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	Diuretics Combined n=40 participants at risk 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.
Renal and urinary disorders Hypokalemia	20.0% 8/40 • Number of events 8 • All-cause mortality was assessed at hospitalisation and during follow-up which lasted an average of 182 days. Serious adverse events and other adverse events were assessed during the 4 days that the intervention lasted. We assessed serious adverse events and other adverse events through daily clinical evaluation by one member of the nephrology team in charge and daily laboratory testing for serum creatinine, urea, glucose, sodium, potassium, chlorine, calcium, phosphorous, arterial or venous blood gas, and complete blood count. All cause mortality during follow-up was assessed through monthly phone calls to patients and/or searching at Hospital electronic records.	17.5% 7/40 • Number of events 7 • All-cause mortality was assessed at hospitalisation and during follow-up which lasted an average of 182 days. Serious adverse events and other adverse events were assessed during the 4 days that the intervention lasted. We assessed serious adverse events and other adverse events through daily clinical evaluation by one member of the nephrology team in charge and daily laboratory testing for serum creatinine, urea, glucose, sodium, potassium, chlorine, calcium, phosphorous, arterial or venous blood gas, and complete blood count. All cause mortality during follow-up was assessed through monthly phone calls to patients and/or searching at Hospital electronic records.
Renal and urinary disorders Hyponatremia	45.0% 18/40 • Number of events 18 • All-cause mortality was assessed at hospitalisation and during follow-up which lasted an average of 182 days. Serious adverse events and other adverse events were assessed during the 4 days that the intervention lasted. We assessed serious adverse events and other adverse events through daily clinical evaluation by one member of the nephrology team in charge and daily laboratory testing for serum creatinine, urea, glucose, sodium, potassium, chlorine, calcium, phosphorous, arterial or venous blood gas, and complete blood count. All cause mortality during follow-up was assessed through monthly phone calls to patients and/or searching at Hospital electronic records.	45.0% 18/40 • Number of events 18 • All-cause mortality was assessed at hospitalisation and during follow-up which lasted an average of 182 days. Serious adverse events and other adverse events were assessed during the 4 days that the intervention lasted. We assessed serious adverse events and other adverse events through daily clinical evaluation by one member of the nephrology team in charge and daily laboratory testing for serum creatinine, urea, glucose, sodium, potassium, chlorine, calcium, phosphorous, arterial or venous blood gas, and complete blood count. All cause mortality during follow-up was assessed through monthly phone calls to patients and/or searching at Hospital electronic records.
Renal and urinary disorders Metabolic alkalosis	30.0% 12/40 • Number of events 12 • All-cause mortality was assessed at hospitalisation and during follow-up which lasted an average of 182 days. Serious adverse events and other adverse events were assessed during the 4 days that the intervention lasted. We assessed serious adverse events and other adverse events through daily clinical evaluation by one member of the nephrology team in charge and daily laboratory testing for serum creatinine, urea, glucose, sodium, potassium, chlorine, calcium, phosphorous, arterial or venous blood gas, and complete blood count. All cause mortality during follow-up was assessed through monthly phone calls to patients and/or searching at Hospital electronic records.	30.0% 12/40 • Number of events 12 • All-cause mortality was assessed at hospitalisation and during follow-up which lasted an average of 182 days. Serious adverse events and other adverse events were assessed during the 4 days that the intervention lasted. We assessed serious adverse events and other adverse events through daily clinical evaluation by one member of the nephrology team in charge and daily laboratory testing for serum creatinine, urea, glucose, sodium, potassium, chlorine, calcium, phosphorous, arterial or venous blood gas, and complete blood count. All cause mortality during follow-up was assessed through monthly phone calls to patients and/or searching at Hospital electronic records.

Additional Information

Dr Jonathan Chavez Iñiguez

hospital civil de guadalajara

Phone: 3313299609

Email: jonarchi_10@hotmail.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place