0.5M Na Lactate Solution in Acute Heart Failure (AHF)

Study Overview
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Brief Summary
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The objective of this trial to see whether: -Cardiac performance (cardiac index and secondary outcomes)can be improved in patients with acute heart failure (AHF) and symptoms and consequences of fluid overload (pulmonary and interstitial edema) and poor peripheral perfusion can be reduced by: Providing lactate as a substrate(Improve cardiac index) Simultaneously restoring optimal preload Optimal standard treatment will be achieved in both arms with the use of current best treatment protocol for AHF as per independent treating physician. 4. To assess effects of 0.5M Na lactate (Totilac) on plasma and urine biological parameters (sodium, potassium, chloride, pH, bicarb, base excess, albumin) 5. To assess effects of 0.5M Na lactate on morbidity and mortality.

Detailed Description
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Acute heart failure is a critical illness for which current treatments are suboptimal. The various symptoms are related to inadequate cardiac output and usually include left ventricular overload with pulmonary oedema, interstitial fluid accumulation and tissue oedema (as indicated by frequent hyponatremia and hypoalbuminemia) and insufficient peripheral perfusion frequently manifesting as cold extremities and low urine output. The current treatment of this syndrome is based on diuretics, vasodilators and/or inotropes, but fluid administration is also required to optimise the intravascular volume state and to reverse shock if present. Therefore management of body fluid balance remains a challenge since treatment aims to simultaneously maintain or improve intravascular volume and decrease body fluid excess and oedema. The purpose of the present study is to assess in a prospective randomised trial the efficacy and safety of a newly designed crystalloid solution, 0.5 M sodium lactate, with properties potentially able to improve multiple pathophysiological aspects of AHF, as compared to the use of standard crystalloid solution Compound Sodium Lactate (mildly hypoosmolar   274 mOsm/L and isotonic).

Official Title
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A Phase 2, Randomised, Single-Blind, Placebo-controlled Study of Half Molar Sodium Lactate Solution in the Treatment of Subjects With Acute Heart Failure

Conditions
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Acute Heart Failure

Intervention / Treatment
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* Drug: 0.5M Sodium lactate
* Drug: Hartmann's solution


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age: more than 18 years Heart failure criteria: Left heart failure: as evidenced by 2 out of 3: Left ventricular ejection fraction (LVEF) ≤ 40% and cardiac index ≤ 2.5 L/min/m2 Acute pulmonary oedema of cardiac origin or mechanical ventilation (including CPAP/BIPAP) for respiratory failure of predominantly cardiac origin Need for inotropes/vasopressors for cardiac pump failure OR Right heart failure: as evidenced by 1 out of 2: Bilateral leg oedema above ankles RV failure (low tricuspid annular plane systolic excursion (TAPSE), dilated floppy RV) Poor peripheral perfusion as evidenced by 2 out of 3: Cold mottled skin Low urine output Acutely clouded sensorium/poor mentation Consent obtained from patient or patient's next of kin. Exclusion Criteria: Hypernatremia: [Na] >145 mmol/L Diagnosed hypertrophic obstructive cardiomyopathy Uncorrected severe valvular heart disease Documented third degree heart block, sustained ventricular tachycardia Documented cardiac tamponade Septic shock Acute respiratory distress syndrome (ARDS) Moribund patients likely to die before 24h Patients with major diseases of limited prognosis such as end stage cancer,end-stage liver failure, end stage dialysis dependent renal failure Patients with absolute indication for acute hemodialysis/hemofiltration (pH, K, urea > 35 mmol/L, severe fluid overload in the presence of oliguria < 200 mL/6h. Known pregnancy

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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No

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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 0.5M Sodium lactate<br>A bolus of 0.5M Sodium lactate of 3 ml per kg body weight (BW) is administered in 15 minutes, followed by a continuous infusion with 1 ml per kg per hour for 24 hours, i.e. in total 27 ml per kg over 24 hours | Drug: 0.5M Sodium lactate<br>* A bolus of 0.5M Sodium lactate of 3 ml per kg BW is administered in 15 minutes, followed by a continuous infusion with 1 ml per kg per hour for 24 hours, i.e. in total 27 ml per kg over 24 hours<br>* Other names: Totilac;|
| Active Comparator: Hartmann's solution<br>Hartmann's solution of 3 ml per kg BW is administered in 15 minutes. There is NO continuous infusion infused thereafter; i.e. in total 3 ml per kg over 24 hours | Drug: Hartmann's solution<br>* Hartmann's solution of 3 ml per kg BW is administered in 15 minutes, No infusion thereafter i.e. in total 3 ml per kg over 24 hours<br>* Other names: Compound Sodium Lactate;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy | Improvement in cardiac output measured by transthoracic echocardiography at 24 hours from initiation of study drug infusion | Baseline till 24 hours from first loading of study drug | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| mortality | range of efficacy and safety parameters | up to 3 month | 
| acid base and electrolytes, fluid balance | the effect on on pH, base excess, bicarbonate, sodium, potassium, phosphate, chloride and lactate will be assessed during the study period | 48 hours | 
| organ function | effect on respiratory function assessed by time on ventilatory support and renal function measured by creatinine level over 48 hours will be assessed | 48 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Sodium Lactate, Acute, Heart, Failure, Perfusion