Hypertonic Saline Solution to Prevent Acute Kidney Injury After Heart Transplantation

Study Overview
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Brief Summary
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The goal of this study is to evaluate if hypertonic saline solution can prevent or attenuate acute kidney injury after heart transplantation in the early postoperative phase.

Detailed Description
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Acute kidney injury (AKI) is a frequent complication immediately after heart transplantation (HT), with incidence rates between 40-70%. Several factors contribute to this complication, such as hypervolemia, hyperactivation of renin-angiotensin-aldosterone system (RASS) and low cardiac output. Hypertonic saline solution (HSS) can reduce diuretic resistance, increase urinary output and improve renal function in hypervolemic status such as acute heart failure. Therefore, the investigators hypothesized that the use of HSS could prevent or attenuate AKI after heart transplantation in the early postoperative phase. The investigators aim to randomize 74 patients to receive 150 mL of HSS 3,5% or placebo (saline solution 0,9%) twice daily for 3 days after HT. Renal function, right ventricular echocardiographic parameters and pulmonary artery catheter parameters will be assessed. Patients will be followed-up until 30 days, or death.

Official Title
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Use of Hypertonic Saline Solution to Prevent Acute Kidney Injury After Heart Transplantation

Conditions
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Heart Transplantation, Acute Kidney Injury

Intervention / Treatment
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* Drug: Sodium chloride solution 3,5%
* Drug: Sodium chloride solution 0,9%


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Hospitalized patients submitted to orthotopic heart transplantation (HT) Exclusion Criteria: Requirement of renal replacement therapy at the time of HT Requirement of extracorporeal membrane oxygenation (ECMO) before or immediately after HT Severe peri-operative mechanical complications Double transplant (e.g. heart-kidney or heart-lung) Hypernatremia (Na ≥ 145) Severe hyponatremia (Na ≤ 120)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Hypertonic Saline Solution 3,5% (HSS)<br> | Drug: Sodium chloride solution 3,5%<br>* Patients will receive 150 mL HSS 3,5% intravenous twice daily for 3 days after heart transplantation.<br>|
| Placebo Comparator: Normal Saline Solution (NS)<br> | Drug: Sodium chloride solution 0,9%<br>* Patients will receive 150 mL NS 0,9% intravenous twice daily for 3 days after heart transplantation.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Prevention of acute kidney injury | Demonstrate a peak value of creatinine 30% lower in the active arm | Days 3 -7 post-transplantation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mortality | Incidence of all cause mortality during the first 30 days after start of the study | 30 days | 
| Incidence of acute kidney injury requiring hemodialysis | Rate of patients which required hemodialysis during the first 30 days after start of the study | 30 days | 
| Intensive care unit (ICU) length of stay | The time frame between start of the study and ICU discharge will be calculated. | During ICU stay, an average of 5 days | 
| Time to wean inotropes and vasopressors | Time to wean all inotropes and vasopressors will be calculated. | During ICU stay, an average of 5 days | 
| Incidence of right ventricular dysfunction | Right ventricular dysfunction will be assessed through the following echocardiographic parameters: Tricuspid annular plane systolic excursion (TAPSE; normal ≥1.7 cm); Tricuspid annular velocity (S') (normal ≥9.5 cm/s); Fractional area change (FAC; normal ≥35 percent); Right Ventricle basal diameter (normal ≤4.1 cm) | Until day 5 post-transplantation | 
| Hypertonic saline solution (HSS) hemodynamic effect | Pulmonary artery catheter measures will be assessed before HSS infusion, immediately after HSS infusion and 30 min after HSS infusion. The following measures will be assessed: Right atrial pressure (RAP) Systolic pulmonary artery pressure (sPAP) Diastolic pulmonary artery pressure (dPAP) Mean pulmonary artery pressure (mPAP) Pulmonary artery wedge pressure (PCWP) Cardiac output (CO) | Until day 3 post-transplantation |