Clinical trial NCT01981655: 0.5M Na Lactate Solution in Acute Heart Failure (AHF)
Official title: A Phase 2, Randomised, Single-Blind, Placebo-controlled Study of Half Molar Sodium Lactate Solution in the Treatment of Subjects With Acute Heart Failure
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Acute Heart Failure
Keywords: Sodium Lactate
Acute
Heart
Failure
Perfusion
Lead sponsor: Nepean Blue Mountains Local Health District
Sponsor class: OTHER
Collaborators: name: Innogene Kalbiotech Pte. Ltd
First posted: 2013-11-11
Enrollment: 41
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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:

1. Providing lactate as a substrate(Improve cardiac index)
2. 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: * 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).

Eligibility criteria: 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

Primary outcomes:
measure: Efficacy
timeFrame: Baseline till 24 hours from first loading of study drug
Secondary outcomes:
measure: mortality
timeFrame: up to 3 month
measure: acid base and electrolytes, fluid balance
timeFrame: 48 hours
measure: organ function
timeFrame: 48 hours
Other outcomes:
Locations:
city: Penrith
country: Australia
facility: Dept. of Intensive Care, Nepean Hosp., U Sydney
state: New South Wales
Study officials:
affiliation: Dept. of Intensive Care, Nepean Hosp., U Sydney, Penrith, NSW, Australia
name: Marek Nalos, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Nalos M, Leverve X, Huang S, Weisbrodt L, Parkin R, Seppelt I, Ting I, Mclean A. Half-molar sodium lactate infusion improves cardiac performance in acute heart failure: a pilot randomised controlled clinical trial. Crit Care. 2014 Mar 25;18(2):R48. doi: 10.1186/cc13793.