NCT02133105

Brief Summary

Although inotropes have a favorable effect on central hemodynamics in patients with heart failure, their effect on renal hemodynamics is incompletely defined. The purpose of this study is to evaluate the efficacy of a 75 min intravenous infusion of levosimendan compared to a 75 min infusion of dobutamine on renal hemodynamics and function in patients with chronic heart failure and signs of cardiorenal syndrome. The investigators hypothesis is that patients treated with levosimendan will show greater increases in renal blood flow and glomerular filtration rate (GFR) than those treated with dobutamine.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
33

participants targeted

Target at below P25 for phase_3

Timeline
Completed

Started Apr 2014

Typical duration for phase_3

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

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Study Timeline

Key milestones and dates

Study Start

First participant enrolled

April 1, 2014

Completed
1 month until next milestone

First Submitted

Initial submission to the registry

May 5, 2014

Completed
2 days until next milestone

First Posted

Study publicly available on registry

May 7, 2014

Completed
3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 1, 2017

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

May 1, 2017

Completed
Last Updated

February 25, 2020

Status Verified

February 1, 2020

Enrollment Period

3.1 years

First QC Date

May 5, 2014

Last Update Submit

February 24, 2020

Conditions

Cardiorenal Syndrome

Keywords

Heart failureRenal failureInotropic drugsLevosimendanDobutamine

Outcome Measures

Primary Outcomes (2)

  • Change in renal blood flow

    Para-aminohippuric acid (PAH) infusion clearance

    75 min minus baseline

  • Change in glomerular filtration rate

    Chrome-ethylenediaminetetraacetic acid (EDTA) infusion clearance

    75 min minus baseline

Secondary Outcomes (4)

  • Change in renal vascular resistance

    75 min minus baseline

  • Change in central hemodynamics

    75 min minus baseline

  • Change in renal oxygen consumption and oxygen extraction

    75 min minus baseline

  • Change in filtration fraction

    75 min minus baseline

Study Arms (2)

Levosimendan

ACTIVE COMPARATOR

Levosimendan administration is initiated with a loading dose of 12μg/kg given over 10 min followed by a continuous infusion of 0.1 μg/kg/min for 65 min.

Drug: Levosimendan

Dobutamine

ACTIVE COMPARATOR

Dobutamine is given as a continuous infusion without a bolus dose. The infusion rate is started at 5.0 μg/kg/min for 10 minutes, and thereafter increased to 7,5 μg/kg/min for 65 min.

Drug: Dobutamine

Interventions

LevosimendanDRUG
Also known as: Simdax
Levosimendan
DobutamineDRUG
Also known as: Dobutrex
Dobutamine

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Written, signed and dated informed consent
  • Male and Female subjects ≥18 years of age
  • Chronic congestive heart failure scheduled for right sided cardiac catheterization
  • Left ventricular ejection fraction ≤ 40% determined by echocardiography
  • Elevation of N Terminal-proBNP ≥ 500 ng/L
  • Cardiorenal syndrome (30ml/min ≤ estimated GFR ≤ 80 ml/min (MDRD)

You may not qualify if:

  • Acute heart failure, untreated
  • Systolic blood pressure \< 80 mmHg
  • Tachycardia above 100 bpm
  • Angina Canadian Cardiovascular Society (CCS) class III or higher
  • Aortic stenosis
  • Hypertrophic cardiomyopathy
  • Restrictive cardiomyopathy
  • The presence of kidney disease diagnosed before heart failure
  • Administration of radiographic contrast \< 1 week
  • Radiographic contrast allergy
  • In the Investigator's opinion, the patient has a clinically significant disease that could be adversely affected by study participation

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Sahlgrenska University Hospital

Gothenburg, 41345, Sweden

Location

Related Publications (5)

  • Savarese G, Lund LH. Global Public Health Burden of Heart Failure. Card Fail Rev. 2017 Apr;3(1):7-11. doi: 10.15420/cfr.2016:25:2.

    PMID: 28785469RESULT

  • Hillege HL, Nitsch D, Pfeffer MA, Swedberg K, McMurray JJ, Yusuf S, Granger CB, Michelson EL, Ostergren J, Cornel JH, de Zeeuw D, Pocock S, van Veldhuisen DJ; Candesartan in Heart Failure: Assessment of Reduction in Mortality and Morbidity (CHARM) Investigators. Renal function as a predictor of outcome in a broad spectrum of patients with heart failure. Circulation. 2006 Feb 7;113(5):671-8. doi: 10.1161/CIRCULATIONAHA.105.580506.

    PMID: 16461840RESULT

  • Smith GL, Shlipak MG, Havranek EP, Masoudi FA, McClellan WM, Foody JM, Rathore SS, Krumholz HM. Race and renal impairment in heart failure: mortality in blacks versus whites. Circulation. 2005 Mar 15;111(10):1270-7. doi: 10.1161/01.CIR.0000158131.78881.D5.

    PMID: 15769768RESULT

  • Hillege HL, Girbes AR, de Kam PJ, Boomsma F, de Zeeuw D, Charlesworth A, Hampton JR, van Veldhuisen DJ. Renal function, neurohormonal activation, and survival in patients with chronic heart failure. Circulation. 2000 Jul 11;102(2):203-10. doi: 10.1161/01.cir.102.2.203.

    PMID: 10889132RESULT

  • Lannemyr L, Ricksten SE, Rundqvist B, Andersson B, Bartfay SE, Ljungman C, Dahlberg P, Bergh N, Hjalmarsson C, Gilljam T, Bollano E, Karason K. Differential Effects of Levosimendan and Dobutamine on Glomerular Filtration Rate in Patients With Heart Failure and Renal Impairment:A Randomized Double-Blind Controlled Trial. J Am Heart Assoc. 2018 Aug 21;7(16):e008455. doi: 10.1161/JAHA.117.008455.

    PMID: 30369310DERIVED

MeSH Terms

Conditions

Cardio-Renal SyndromeHeart FailureRenal Insufficiency

Interventions

SimendanDobutamine

Condition Hierarchy (Ancestors)

Kidney DiseasesUrologic DiseasesFemale Urogenital DiseasesFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital DiseasesMale Urogenital DiseasesHeart DiseasesCardiovascular Diseases

Intervention Hierarchy (Ancestors)

HydrazonesHydrazinesOrganic ChemicalsPyridazinesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsCatecholaminesAminesPhenethylaminesEthylaminesCatecholsPhenolsBenzene DerivativesHydrocarbons, AromaticHydrocarbons, CyclicHydrocarbons

Study Officials

  • Kristjan Karason, MD, PhD

    Sahlgrenska University Hospital, Department of Cardiology

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

May 5, 2014

First Posted

May 7, 2014

Study Start

April 1, 2014

Primary Completion

May 1, 2017

Study Completion

May 1, 2017

Last Updated

February 25, 2020

Record last verified: 2020-02

Data Sharing

IPD Sharing
Will share
Shared Documents
STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE

Locations

SE(1)