The Effect in Renal Function on Patients With Type 1 Cardiorenal Syndrome Treated With Two Strategies of Furosemide.

The Effect in Renal Function on Patients With Type 1 Cardiorenal Syndrome Treated With Two Strategies of Furosemide. A Randomized Controled Trial

In double-blind clinical trial, determine renal recovery with two different furosemide strategies in patients with type 1 cardiorenal syndrome.

Study Overview

• Status: Completed
• Conditions: Cardiorenal Syndrome
• Intervention / Treatment: Drug: Furosemide intravenous solution; Drug: Chlortalidone; Drug: Spironolactone

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.

• Study Type: Interventional
• Enrollment (Actual): 80
• Phase: Phase 2

Contacts and Locations

Study Locations

• Mexico
  • Jalisco
    • Guadalajara, Jalisco, Mexico, 44240
      • HCG
    • Guadalajara, Jalisco, Mexico, 44240
      • Hospital Civil de Guadalajara

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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	Drug: Furosemide intravenous solution; 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.
Experimental: 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 3 furosemide 100mg / day infused with 100cc of Hartmann solution + Chlortalidone 50mg VO every 24 hours + Spironolactone 50mg VO every 24 hrs.	Drug: Furosemide intravenous solution; 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.; Drug: Chlortalidone; One 50 mg pill administrated every 24 hours in group B; Drug: Spironolactone; One 50 mg pill administrated every 24 hours in group B

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)	Up to 96 hours after intervention started

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	96 hours after intervention started
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	96 hours 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
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	Up to 96 hours after intervention started
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	Up to 3 days after intervention started
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	Up to 4 days after intervention started
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	Up to 96 hours after intervention started

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	96 hours after intervention started
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	96 hours after intervention started
Number of Patients That Achieved >30% Reduction in Brain Natriuretic Compared With Baseline Levels	Baseline levels were defined as the measurement at hospital admission	Up to 96 hours after intervention started
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	From the beginning of intervention and before 96 hours after that
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.	96 hours 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.	Calculated as serum sodium levels at day one of intervention minus serum sodium levels at 96 hrs after intervention started.	96 hours 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.	Calculated as serum potassium levels at day one of intervention minus serum potassium levels at 96 hrs after intervention started.	96 hours 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.	Calculated as serum chloride levels at day one of intervention minus serum chloride levels at 96 hrs after intervention started.	96 hours 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.	Calculated as serum magnesium levels at day one of intervention minus serum magnesium levels at 96 hrs after intervention started.	96 hours 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.	Calculated as serum calcium levels at day one of intervention minus serum calcium levels at 96 hrs after intervention started.	96 hours after intervention started
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.	96 hours 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.	Calculated as serum bicarbonate levels at day one of intervention minus bicarbonate levels at 96 hrs after intervention started.	96 hours 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.	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.	96 hours 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.	Calculated as serum lactate levels at day one of intervention minus serum lactate levels at 96 hrs after intervention started.	96 hours after intervention started

Collaborators and Investigators

• Sponsor: Hospital Civil de Guadalajara

Publications and helpful links

General Publications

• Chavez-Iniguez JS, Ibarra-Estrada M, Sanchez-Villaseca S, Romero-Gonzalez G, Font-Yanez JJ, De la Torre-Quiroga A, de Quevedo AA, Romero-Munoz A, Maggiani-Aguilera P, Chavez-Alonso G, Gomez-Fregoso J, Garcia-Garcia G. The Effect in Renal Function and Vascular Decongestion in Type 1 Cardiorenal Syndrome Treated with Two Strategies of Diuretics, a Pilot Randomized Trial. BMC Nephrol. 2022 Jan 3;23(1):3. doi: 10.1186/s12882-021-02637-y.

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2017
• Primary Completion (Actual): April 1, 2020
• Study Completion (Actual): April 1, 2020

Study Registration Dates

• First Submitted: August 22, 2017
• First Submitted That Met QC Criteria: May 16, 2020
• First Posted (Actual): May 19, 2020

Study Record Updates

• Last Update Posted (Actual): September 14, 2020
• Last Update Submitted That Met QC Criteria: August 21, 2020
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Kidney Diseases; Urologic Diseases; Disease; Renal Insufficiency; Heart Failure; Syndrome; Cardio-Renal Syndrome; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Natriuretic Agents; Membrane Transport Modulators; Diuretics; Hormone Antagonists; Mineralocorticoid Receptor Antagonists; Diuretics, Potassium Sparing; Sodium Chloride Symporter Inhibitors; Sodium Potassium Chloride Symporter Inhibitors; Spironolactone; Furosemide; Chlorthalidone
• Other Study ID Numbers: 112/17

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No