0.5M Na Lactate Solution in Acute Heart Failure (AHF) (SOLACE1)

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

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.

Study Overview

• Status: Completed
• Conditions: Acute Heart Failure
• Intervention / Treatment: Drug: 0.5M Sodium lactate; Drug: Hartmann's solution

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).

• Study Type: Interventional
• Enrollment (Actual): 41
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Penrith, New South Wales, Australia, 2751
      • Dept. of Intensive Care, Nepean Hosp., U Sydney

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:

• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: 0.5M Sodium lactate; 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; 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; Other Names: Totilac
ACTIVE_COMPARATOR: Hartmann's solution; 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; 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; Other Names: Compound Sodium Lactate

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Nepean Blue Mountains Local Health District
• Collaborators: Innogene Kalbiotech Pte. Ltd
• Investigators: Principal Investigator: Marek Nalos, MD, Dept. of Intensive Care, Nepean Hosp., U Sydney, Penrith, NSW, Australia

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: December 1, 2009
• Primary Completion (ACTUAL): February 1, 2013
• Study Completion (ACTUAL): August 1, 2013

Study Registration Dates

• First Submitted: August 13, 2013
• First Submitted That Met QC Criteria: November 5, 2013
• First Posted (ESTIMATE): November 11, 2013

Study Record Updates

• Last Update Posted (ESTIMATE): November 13, 2013
• Last Update Submitted That Met QC Criteria: November 9, 2013
• Last Verified: November 1, 2013

More Information

Terms related to this study

• Keywords: Heart; Acute; Perfusion; Failure; Sodium Lactate
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure
• Other Study ID Numbers: SOLACE1