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

Study Overview
=================
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.

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

Conditions
-----------------
Cardiorenal Syndrome

Intervention / Treatment
-----------------
* Drug: Furosemide intravenous solution
* Drug: Chlortalidone
* Drug: Spironolactone


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Its a randomized, controlled, phase II, 2-arm, double-blind clinical trial
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GROUP A<br>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<br>* 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.<br>|
| Experimental: GROUP B<br>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<br>* 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.<br>Drug: Chlortalidone<br>* One 50 mg pill administrated every 24 hours in group B<br>Drug: Spironolactone<br>* One 50 mg pill administrated every 24 hours in group B<br>|

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 |