NCT04170855

Brief Summary

Diuretic therapy is the cornerstone of the management of fluid overload in heart failure. Resistance to diuretic therapy is the most common reason for treatment failure in patients affected by the combination of heart failure and kidney disease. Currently, there is no way of predicting whether heart failure patients will develop resistance to diuretic therapy and what dose of diuretic is necessary to overcome diuretic resistance. Answering these questions would allow doctors to be able to prescribe an accurate dose of diuretic therapy to prevent diuretic resistance and potential side effects of an excessive diuretic dose. With magnetic resonance imaging, it is possible to measure the kidney sodium (salt) content and observe the diuretic response in patients with heart failure and kidney disease. The investigators speculate that measuring kidney sodium content will allow to predict diuretic response in these patients. The aim of this study is to compare the kidney sodium content in patients with chronic cardiorenal syndrome with and without diuretic resistance. Secondly, in a sample of patients with diagnosed diuretic resistance,the aim will be to observe the changes in kidney sodium content induced by an additional dose of diuretic therapy and to observe whether these changes are associated with a response to diuretic therapy.

Trial Health

75
On Track

Trial Health Score

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

Enrollment
50

participants targeted

Target at P25-P50 for not_applicable

Timeline
9mo left

Started Oct 2020

Longer than P75 for not_applicable

Geographic Reach
1 country

1 active site

Status
active not recruiting

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

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress87%
Oct 2020Feb 2027

First Submitted

Initial submission to the registry

October 21, 2019

Completed
1 month until next milestone

First Posted

Study publicly available on registry

November 20, 2019

Completed
11 months until next milestone

Study Start

First participant enrolled

October 20, 2020

Completed
6.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 30, 2026

Expected
2 months until next milestone

Study Completion

Last participant's last visit for all outcomes

February 28, 2027

Last Updated

May 4, 2026

Status Verified

April 1, 2026

Enrollment Period

6.2 years

First QC Date

October 21, 2019

Last Update Submit

April 28, 2026

Conditions

Cardio-Renal Syndrome

Keywords

kidney sodium contentSodium MRI

Outcome Measures

Primary Outcomes (1)

  • Medullary sodium concentration

    To demonstrate a statistically significant difference in medullary sodium concentration of at least 100 mmol/L between patients with chronic cardiorenal syndrome who are responsive versus patients who are resistant to their current diuretic therapy.

    Through MRI, an average of 60 minutes

Secondary Outcomes (9)

  • Corticomedullary sodium gradient

    Through MRI, an average of 60 minutes

  • Change in medullary sodium concentration

    Through MRI, an average of 60 minutes

  • Change in corticomedullary sodium gradient

    Through MRI, an average of 60 minutes

  • Correlation between kidney sodium content and renal function

    Through one study visit, and average of 3 hours

  • Correlation between kidney sodium content and biological cardiac biomarker

    Through one study visit, and average of 3 hours

  • +4 more secondary outcomes

Study Arms (1)

Furosemide Injection

OTHER

Patients with diuretic resistance: The presence of diuretic resistance, defined as having clinical signs of fluid overload despite diuretic therapy (this information is routinely collected at each clinical visit). "Fluid overload" is defined as the presence of at least two of the following clinical features: * Peripheral or sacral oedema * Jugular venous distension ≥ 7 cm * Radiographic pulmonary oedema or pleural effusion * Enlarged liver or ascites * Pulmonary rales, paroxysmal nocturnal dyspnoea, or orthopnoea * Point of Care UltraSound (POCUS) evidence of congestion. Inferior Vena Cava diameter \>2.5 cm and/or failure to collapse at least 50% with sharp inspiration

Drug: Furosemide Injection

Interventions

Furosemide InjectionDRUG

We will measure kidney sodium content in patient with cardiorenal syndrome. we will inject within the week of this first measurement furosemide only in patient who will be resistant to diuretics (Based on these parameters, diuretic response will be defined as: * A reduction in fractional spot urinary sodium * An increase in urinary volume * A \>1 kg reduction in body weight within 24 hours from diuretic administration (extrapolation of guidance on management of acute HF) and we will do another measurement of kidney sodium content after furosemide injection.

Furosemide Injection

Eligibility Criteria

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

You may qualify if:

  • Clinico-pathological diagnosis of heart failure
  • Age ≥ 18 years
  • Estimated GFR ≥ 15 mL/min/1.73m2
  • Receiving loop diuretics for at least a week at ≥ 40 mg/day (furosemide) or 2 mg/day (bumetanide), either orally or intravenously
  • Willing and able to provide consent

You may not qualify if:

  • Additional diuretic types other than spironolactone/epleronone/metolazone/finerenone
  • Liver disease with hepato-renal syndrome
  • Pregnant, breastfeeding or intending pregnancy
  • Kidney malformation leading to chronic kidney disease (for example polycystic kidney)
  • Unable to provide consent
  • · Hypokalemia (serum potassium \<3.5 mmol/l)

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Heart Failure Clinic | St. Joseph's Health Care London

London, Ontario, N6A 3N3, Canada

Location

Related Publications (9)

  • Mosterd A, Hoes AW. Clinical epidemiology of heart failure. Heart. 2007 Sep;93(9):1137-46. doi: 10.1136/hrt.2003.025270.

    PMID: 17699180BACKGROUND

  • Chioncel O, Mebazaa A, Harjola VP, Coats AJ, Piepoli MF, Crespo-Leiro MG, Laroche C, Seferovic PM, Anker SD, Ferrari R, Ruschitzka F, Lopez-Fernandez S, Miani D, Filippatos G, Maggioni AP; ESC Heart Failure Long-Term Registry Investigators. Clinical phenotypes and outcome of patients hospitalized for acute heart failure: the ESC Heart Failure Long-Term Registry. Eur J Heart Fail. 2017 Oct;19(10):1242-1254. doi: 10.1002/ejhf.890. Epub 2017 Apr 30.

    PMID: 28463462BACKGROUND

  • McCullough PA, Kellum JA, Haase M, Muller C, Damman K, Murray PT, Cruz D, House AA, Schmidt-Ott KM, Vescovo G, Bagshaw SM, Hoste EA, Briguori C, Braam B, Chawla LS, Costanzo MR, Tumlin JA, Herzog CA, Mehta RL, Rabb H, Shaw AD, Singbartl K, Ronco C. Pathophysiology of the cardiorenal syndromes: executive summary from the eleventh consensus conference of the Acute Dialysis Quality Initiative (ADQI). Contrib Nephrol. 2013;182:82-98. doi: 10.1159/000349966. Epub 2013 May 13.

    PMID: 23689657BACKGROUND

  • Clark AL, Kalra PR, Petrie MC, Mark PB, Tomlinson LA, Tomson CR. Change in renal function associated with drug treatment in heart failure: national guidance. Heart. 2019 Jun;105(12):904-910. doi: 10.1136/heartjnl-2018-314158.

    PMID: 31118203BACKGROUND

  • Jamison RL. The renal concentrating mechanism: micropuncture studies of the renal medulla. Fed Proc. 1983 May 15;42(8):2392-7.

    PMID: 6341087BACKGROUND

  • Faris RF, Flather M, Purcell H, Poole-Wilson PA, Coats AJ. Diuretics for heart failure. Cochrane Database Syst Rev. 2012 Feb 15;(2):CD003838. doi: 10.1002/14651858.CD003838.pub3.

    PMID: 22336795BACKGROUND

  • Maril N, Rosen Y, Reynolds GH, Ivanishev A, Ngo L, Lenkinski RE. Sodium MRI of the human kidney at 3 Tesla. Magn Reson Med. 2006 Dec;56(6):1229-34. doi: 10.1002/mrm.21031.

    PMID: 17089361BACKGROUND

  • Maril N, Margalit R, Mispelter J, Degani H. Sodium magnetic resonance imaging of diuresis: spatial and kinetic response. Magn Reson Med. 2005 Mar;53(3):545-52. doi: 10.1002/mrm.20359.

    PMID: 15723399BACKGROUND

  • Akbari A, Lemoine S, Salerno F, Marcus TL, Duffy T, Scholl TJ, Filler G, House AA, McIntyre CW. Functional Sodium MRI Helps to Measure Corticomedullary Sodium Content in Normal and Diseased Human Kidneys. Radiology. 2022 May;303(2):384-389. doi: 10.1148/radiol.211238. Epub 2022 Feb 8.

    PMID: 35133199DERIVED

MeSH Terms

Conditions

Cardio-Renal Syndrome

Interventions

Furosemide

Condition Hierarchy (Ancestors)

Renal InsufficiencyKidney DiseasesUrologic DiseasesFemale Urogenital DiseasesFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital DiseasesMale Urogenital DiseasesHeart FailureHeart DiseasesCardiovascular Diseases

Intervention Hierarchy (Ancestors)

SulfanilamidesSulfonamidesAmidesOrganic ChemicalsAniline CompoundsAminesSulfonesSulfur Compounds

Study Officials

  • Christopher W McIntyre, MD

    Western University

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
not applicable
Allocation
NA
Masking
NONE
Purpose
DIAGNOSTIC
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Professor of Medicine, Medical Biophysics and Pediatrics

Study Record Dates

First Submitted

October 21, 2019

First Posted

November 20, 2019

Study Start

October 20, 2020

Primary Completion (Estimated)

December 30, 2026

Study Completion (Estimated)

February 28, 2027

Last Updated

May 4, 2026

Record last verified: 2026-04

Data Sharing

IPD Sharing
Will not share

Locations

CA(1)