Does the Sequence of Heart Failure Medication Matter

NCT06637618 | Not Yet Recruiting

• 1 other identifier: CROWD sequence
• Study Type: interventional
• Target: 16,000
• Locations: 0 countries
• Sites: N/A

Brief Summary

This study will tests whether a strategy of upfront prescription of mineralocorticoid receptor antagonists (MRA) is different from usual care, where MRA are usually prescribes as the last drug of the four drug classes used in the treatment of heart failure with reduced cardiac pump function (ace-inhibitor, beta blocker, sodium-glucose-2 inhibitors, MRA). The study is a national study that intends to include all adult Danish patients diagnosed with heart failure and reduced pump function from early 2025 til early 2029. Treatment strategy will be decided by randomisation, where each heart failure clinic is randomised to one of the two strategies (upfront MRA vs. usual care) for one year, followed by cross-over to the other treatment strategy for one year. Patients will be followed according to usual care at their respective heart failure clinic. Study-specific followup will be conducted through the Danish registries for a minimum of two years. The primary goal of the study is to evaluate whether one of the two treatment strategies leads to fewer hospitalisations for heart failure and/or death at one year after study entry. Other goals of the study is to evaluate whether one of the two strategies leads to less kidney disease, improved quality of life and improved cost-effectiveness

Conditions

Heart Failure, Reduced Ejection Fraction

Keywords

heart failure; pharmacology; cluster randomised controlled clinical trial; mineralocorticoid receptor antagonist; beta blocker; ace inhibitor; sglt2 inhibitor

Outcome Measures

Primary Outcomes (1)

• Combined one year all-cause mortality or first hospitalization for worsening heart failure.

  From date of enrollment until the date of first hospitalization for worsening heart failure or date of death from any cause, whichever comes first, assessed up to 200 months

Secondary Outcomes (5)

• All-cause mortality

  From date of enrollment until the date of first hospitalization for worsening heart failure or date of death from any cause, whichever comes first, assessed up to 200 months

• First hospitalization for heart failure

  From date of enrollment until the date of first hospitalization for worsening heart failure or date of death from any cause, whichever comes first, assessed up to 200 months

• Total number of acute hospitalizations

  From date of enrollment until the date of first hospitalization for worsening heart failure or date of death from any cause, whichever comes first, assessed up to 200 months

• Need for dialysis

  From date of enrollment until the date of first hospitalization for worsening heart failure or date of death from any cause, whichever comes first, assessed up to 200 months

• Change in income

  From date of enrollment until the date of first hospitalization for worsening heart failure or date of death from any cause, whichever comes first, assessed up to 200 months

Study Arms (2)

standard care

ACTIVE COMPARATOR

standard care, with physicians choice of the sequence and up-titration of heart failure medications (ACE-inhibitor, beta-blocker, mineralocorticoid receptor antagonist, SGLT2-inhibitor)

Behavioral: up front use of mineralocorticoid receptor antagonist

Up-front prescription of mineralocorticoid receptor antagonist, no later than the first ambulatory v

EXPERIMENTAL

Up-front prescription of mineralocorticoid receptor antagonist, no later than the first ambulatory visit to the heart failure clinic. Earlier use during initial hospitalization is encouraged, but not mandatory

Behavioral: up front use of mineralocorticoid receptor antagonist

Interventions

up front use of mineralocorticoid receptor antagonist BEHAVIORAL

the sequence of which the four drug classes are prescribed will differ, where the intervention is early use of MRA, where the control group will receive standard care, where MRA are usually prescribed last

Up-front prescription of mineralocorticoid receptor antagonist, no later than the first ambulatory v; standard care

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• All patients ≥18 years old who are newly diagnosed with HFrEF and allocated to an outpatient clinic for up-titration of guideline-directed medical therapy for HFrEF at participating cardiology departments

Sponsors & Collaborators

• Aarhus University Hospital: lead
• Rigshospitalet, Denmark: collaborator
• Odense University Hospital: collaborator
• Aalborg University Hospital: collaborator
• Hillerod Hospital, Denmark: collaborator
• Herlev and Gentofte Hospital: collaborator
• Slagelse Hospital: collaborator
• Bispebjerg Hospital: collaborator
• Naestved Hospital: collaborator
• Svendborg Hospital: collaborator
• Sygehus Lillebaelt: collaborator
• Aabenraa Hospital: collaborator
• Viborg Regional Hospital: collaborator
• Randers Regional Hospital: collaborator
• Regionshospitalet Silkeborg: collaborator
• Regionshospital Nordjylland: collaborator
• Hospitalsenheden Vest: collaborator

MeSH Terms

Conditions

Heart Failure, Systolic; Heart Failure

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Central Study Contacts

Mads J Andersen, MD, PhD

CONTACT

+45 78450000; Andersen.Mads@rm.dk

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Senior Registrar, MD PhD

Model Details: An open-label cluster randomised crossover clinical trial, assessing the effect of upfront use of mineralocorticoid antagonists versus usual sequencing of heart failure medication

Study Record Dates

• First Submitted: September 13, 2024
• First Posted: October 15, 2024
• Study Start: February 1, 2025
• Primary Completion (Estimated): January 31, 2029
• Study Completion (Estimated): February 1, 2030
• Last Updated: October 15, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share