Use of a Novel SUBCUTaneous Preparation of Furosemide to Facilitate Early Supported Discharge of Patients With Heart Failure (SUBCUT-HF II)

Use of a Novel SUBCUTaneous Preparation of Furosemide to Facilitate Early Supported Discharge of Patients With Heart Failure: a Multicentre, Phase II, Randomised, Parallel Group, Active Comparator Controlled Trial

To investigate whether an early supported discharge strategy for patients admitted to hospital because of HF, using a pH neutral subcutaneous (SC) furosemide formulation (SQINFurosemide) at home (delivered by non-CE marked SQINInfusor), compared to a usual care strategy with intravenous (IV) furosemide in hospital, results in an increased number of days spent alive and out of hospital (DAOH) at 30 days.

Study Overview

• Status: Recruiting
• Conditions: Heart Failure
• Intervention / Treatment: Drug: SQIN-Furosemide; Device: SQIN-Infusor

Detailed Description

HF is associated with frequent and lengthy hospitalisations. These hospitalisations are usually as a result of congestion, and the standard treatment of this is decongestion with intravenous (IV) diuretic (usually furosemide). This is usually delivered in a hospital setting. A new formulation of a pHneutral furosemide (SQIN-Furosemide) that can be delivered subcutaneously (SC) by a small patch pump (SQIN-Infusor) has been developed. Bioavailability of SQIN-Furosemide is similar to IV furosemide. This trial will test the efficacy and safety of novel SC furosemide 30mg/ml (SQIN-Furosemide), delivered in a home environment (compared to usual care strategy with IV furosemide delivered in secondary care) as part of a novel early supported discharge strategy in patients admitted to hospital with HF.

• Study Type: Interventional
• Enrollment (Estimated): 550
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Mark Petrie, MBChB; Phone Number: 0141 330 2427; Email: mark.petrie@glasgow.ac.uk
• Study Contact Backup: Name: Ross Campbell, MBChB; Phone Number: 01413302418; Email: ross.campbell@glasgow.ac.uk

Study Locations

• United Kingdom
  • Scotland
    • Glasgow, Scotland, United Kingdom, G12 8TA
      • Recruiting
      • Glasgow Royal Infirmary
      • Contact: Mark Petrie, MBChB; Phone Number: 01413302418; Email: mark.petrie@glasgow.ac.uk
      • Contact: Joanna Osmanska, MBChB; Email: joanna.osmanska@glasgow.ac.uk
  • Strathclyde
    • Glasgow, Strathclyde, United Kingdom, G51 4TF
      • Recruiting
      • Queen Elizabeth University Hospital
      • Contact: Joanna Osmanska, MBChB; Email: joanna.osmanska@glasgow.ac.uk
      • Contact: Ross Campbell, MBChB; Email: ross.campbell@glasgow.ac.uk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Written informed consent

  • Male or female ≥18 years of age
  • Meet European Society of Cardiology (ESC) criteria for diagnosis of HF1 o Elevated natriuretic peptide (BNP> 100 pg/mL or NTproBNP >300 pg/mL) o Signs and symptoms of HF o Echocardiographic structural or functional abnormality according to ESC guidelines (Appendix B)
  • Have received IV diuretic for treatment of HF within preceding 24 hours
  • Be less than 96 hours after admission to hospital
  • Requiring IV diuretics for a minimum of 24 hours after screening
  • Have an echocardiogram or other assessment of cardiac structure and function within preceding 12 months or at screening
  • Have demonstrated an adequate diuresis with IV diuretic in the preceding 24 hours (defined as any weight loss or > 500 mLs negative fluid balance)
  • Have a home environment that allows the patient to be able to mobilise within their residence and be able to pass urine into their toilet (unless catheterised)
  • Able to operate (or has a caregiver who can operate) SQIN-Infusor (as assessed by training on a dummy device at screening)

Exclusion Criteria:

• Unable to consent due to significant cognitive impairment or lack of capacity

  • Unable to operate SQIN-Infusor (or no caregiver who is able to operate the device)
  • Geographical reasons preventing follow-up visits
  • Pregnancy or breast-feeding
  • Requiring treatment with IV furosemide >200 mg furosemide per day in the opinion of the treating physician
  • Left sided valve disease with planned surgery or percutaneous intervention• Type 1 myocardial infarction during index hospitalisation (participants with type 2 myocardial infarction can be included)2
  • Renal impairment, defined as estimated glomerular filtration rate (eGFR) < 20 mL/min/1.73 m 2 at screening
  • Reasons (other than HF) which may prevent discharge from hospital, such as social circumstances or other significant medical condition (at investigator discretion)
  • Women of childbearing potential
  • Patient on active cardiac transplant waiting list
  • Patient requiring on-going inotropic, vasopressor or intraaortic balloon pump support
  • Potassium <3.0 mmol/L
  • Potassium >6.0 mmol/L
  • Sodium <125 mmol/L
  • Any surgical or medical condition which, in the opinion of the investigator, may pose an undue risk to the subject, interfere with participation in the study or which may affect the integrity of the data

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Usual Care; Open label, 1:1 randomisation to usual care in hospital vs early supported discharge with SQIN-Furosemide administered via SQIN-Infusor. Usual care: Usual care as per institutional practice (including IV diuretics)
Experimental: Early supported discharge; Open label, 1:1 randomisation to usual care in hospital vs early supported discharge with SQIN-Furosemide administered via SQIN-Infusor. Early supported discharge: with SQIN-Furosemide and SQIN-Infusor. SQIN-Furosemide: 80mg of SQIN-Furosemide in each cartridge; 5 hours running time; up to 2 applications in 24h (maximum dose of 160mg of SQIN-Furosemide in 24h). SQIN-Infusor: patient/carer administered.	Drug: SQIN-Furosemide; The investigational furosemide formulation (SQIN-Furosemide) is a Captisol®buffered solution of 80mg furosemide in 2.7 mL (30 mg/mL) at pH 7.4 (range: 7.0 to 7.8). SC infusion will be performed using the SQIN-Infusor which will deliver 2.7 mL of the SQIN-Furosemide formulation (80mg) over approximately 5 hours, using a biphasic delivery profile.; Device: SQIN-Infusor; The investigational device (SQIN-Infusor) is an on-body delivery system that consists of a RU, DU, plus a charger (Figure 2). For the purpose of SUBCUT-HF II trial, the RU will be used for multiple infusions for a single participant. The DU will be used only once per infusion and disposed of. The RU must be charged after each use and will not restart for the next infusion without charging. Charging takes up to 15 minutes. SQIN-Infusor is a bespoke system, adapted from the design of a SC insulin pump. The RU consists of the drive-unit, the controllers, the rechargeable battery, and the user interface.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Days Alive Out of Hospital	Days spent alive and out of hospital (DAOH), from randomisation to 30 days.	30 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Length of index hospitalisation	Length of index hospitalisation	30 days
Days Alive Out of Hospital	Days spent alive and out of hospital (DAOH), from randomisation to 60 days.	60 days
Total number of HF hospitalisations at 60 days	Total number of HF hospitalisations at 60 days	60 days
CV death or first HF hospitalisation at 60 days	CV death or first HF hospitalisation at 60 days	60 days
CV mortality at 60 days	CV mortality at 60 days	60 days
Safety as determined by treatment emergent adverse events (TEAEs) (including serious adverse events [SAEs]) and adverse drug events (ADEs) (including serious adverse drug events [SADEs])	Safety as determined by treatment emergent adverse events (TEAEs) (including serious adverse events [SAEs]) and adverse drug events (ADEs) (including serious adverse drug events [SADEs])	60 days
Any device failures (e.g., adhesive failure and drug delivery failure)	Any device failures (e.g., adhesive failure and drug delivery failure)	60 days
Change in quality of life	Change in quality of life at 60 days (assessed by Kansas City Cardiomyopathy Questionnaire [KCCQ-12]) [0-100]	60 days

Collaborators and Investigators

• Sponsor: NHS Greater Glasgow and Clyde
• Collaborators: University of Glasgow

Study record dates

Study Major Dates

• Study Start (Actual): November 17, 2022
• Primary Completion (Estimated): May 28, 2024
• Study Completion (Estimated): August 30, 2024

Study Registration Dates

• First Submitted: June 10, 2022
• First Submitted That Met QC Criteria: June 10, 2022
• First Posted (Actual): June 15, 2022

Study Record Updates

• Last Update Posted (Actual): April 24, 2024
• Last Update Submitted That Met QC Criteria: April 23, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Natriuretic Agents; Membrane Transport Modulators; Diuretics; Sodium Potassium Chloride Symporter Inhibitors; Furosemide
• Other Study ID Numbers: 2020-004833-19

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No