Efficacy of a Streamlined Heart Failure Optimization Protocol (SHORT)

March 9, 2025 updated by: The Queen Elizabeth Hospital King's Lynn NHS Foundation Trust

Efficacy of a Streamlined Heart Failure Optimisation PRoTocol for Patients with Severely Impaired Left Ventricular Systolic Function, a Randomised Controlled Trial (SHORT Trial)

The SHORT trial compares the current standard optimization protocol to a shortened protocol in a randomized control trial.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

The SHORT trial compares the current standard optimization protocol to a shortened protocol in a randomized control trial. It assesses whether an accelerated protocol leads to faster optimization and a greater degree of optimization.

Study Type

Interventional

Enrollment (Actual)

60

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United Kingdom
    • Norfolk
      • King's Lynn, Norfolk, United Kingdom, PE30 4ET
        • Queen Elizabeth Hospital King's Lynn

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Ejection fraction of less than or equal to 40%
  • Increased NT-proBNP level:
  • ≥ 600 pg per milliliter or
  • ≥400 pg per milliliter if they had been hospitalized for heart failure within the previous 12 months or
  • patients with atrial fibrillation or atrial flutter on baseline electrocardiography were required to have an NT-pro BNP level of at least 900 pg per milliliter, regardless of their history of hospitalization for heart failure or
  • recent heart failure admission or clinical diagnosis of heart failure.
  • Patients who are either naïve to or taking no more than 25% target doses of Beta Blockers or ACEi or ARB before starting the trial.

Exclusion Criteria:

  • Systolic BP of less than 100 mmHg on 2 consecutive measurements
  • Estimated glomerular filtration rate (eGFR) less than 30 ml/min/1.73m2
  • Type 1 diabetes mellitus
  • Cognitive impairment that in the opinion of the investigator may lead the patient to be unable to understand and/or comply with the study medications, procedures and/or follow-up
  • Uncorrected primary valvular disease
  • Active malignancy treatment at time of visit 1
  • Women of child-bearing potential who are not willing to use a medically accepted method of contraception that is reliable in the judgement of the investigator*
  • Women who are pregnant or breastfeeding
  • History of angioedema, or hereditary or idiopathic angioedema
  • Severe hepatic impairment, biliary cirrhosis or cholestasis

  • Patients who are receiving treatment with an aliskiren-containing product who have diabetes mellitus or renal impairment (eGFR <60 ml/min/1.73 m2)

    • Highly effective methods of contraception include implants, injectables, combined oral contraceptives (the participant must have been on a stable dose for at least 3 months before entering the trial), intrauterine device, vasectomised partner, or true sexual abstinence (when this is the preferred and usual lifestyle of the patient and does not include periodic abstinence [e.g. calendar, ovulation, symptothermal or post-ovulation methods]). Use of such methods must be maintained throughout the trial and for 7 days after the end of the trial.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Streamlined protocol arm

Patients are optimized according to the accelerated protocol adapted from and based on the principles proposed by Prof McMurray and Prof Packer (Circulation 2021;143:875-877)

Visit 1: Low dose Beta Blocker started, SGLT2i started & Entresto* started

*The starting dose of Entresto will be determined by the baseline blood pressure (BP) (a dose of 24/26 mg twice daily (BD) is to be started if the systolic BP is less than 110 mmHg otherwise a dose of 49/51 mg BD is to be started)

Visit 2: MRA added if renal function and potassium levels permit (Beta Blocker increased if BP and pulse rate permit)

Visit 3: MRA/Entresto up-titrated if BP and renal function and potassium levels permit (Beta Blocker increased if BP and pulse rate permit)

Visit 4+: Beta Blocker increased if BP and pulse rate permit. Further visits may be required to facilitate a gentle up-titration of Beta Blockers.
Other: Streamlined protocol
A streamlined drug protocol for optimizing heart failure medication
Active Comparator: Standard Arm

Both the current European Society of Cardiology (ESC) and the National Institute of Health and Care Excellence (NICE) guidelines advise that chronic stable heart failure patients with severely impaired left ventricular systolic function should initially be optimized as follows:

Visit 1: Angiotensin-converting enzyme inhibitor (ACEi)/Angiotensin receptor blocker (ARB) and Low dose Beta blocker commenced Visit 2: ACEi/ARB up-titrated; (Beta Blocker up-titrated) Visit 3: ACEi/ARB up-titrated; (Beta Blocker up-titrated) Visit 4: Mineralocorticoid receptor antagonist (MRA) added Visit 5: MRA up-titrated Visit 6: Switch ACEi/ARB to Entresto 49/51 mg twice daily (BD) Visit 7: Modify Entresto dose to 97/103 mg BD Visit 8: Sodium-glucose cotransporter-2 inhibitor (SGLT2i) started
Other: Standard Protocol
Current standard optimization protocol as per NICE and ESC

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Time to point of optimization
Time Frame: Maximum follow-up 6 months

Do patients on the streamlined protocol reach the point of optimization* earlier?

*point of optimization is defined as the point in time at which no medication could be increased further either due to achievement of target doses or limited by symptoms, low heart rate, BP, or raised serum potassium or serum Creatinine.
Maximum follow-up 6 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of appointments required
Time Frame: Maximum follow-up 6 months
Do patients on the streamlined protocol require fewer appointments to reach the point of optimization?
Maximum follow-up 6 months
Composite of cardiovascular death and worsening heart failure
Time Frame: 6 months
Do patients on the streamlined protocol have a lower incidence of the composite endpoint of cardiovascular death and worsening heart failure (defined as hospitalization or an urgent visit resulting in intravenous therapy for heart failure)?
6 months
Degree of optimization reached
Time Frame: Maximum follow-up 6 months

1. Do patients on the streamlined protocol reach a greater "degree of optimization" **?

**degree of optimization is defined as the average percentage of the target doses reached across the four heart failure drug groups at the point of optimization.
Maximum follow-up 6 months
Number of Complications
Time Frame: Maximum follow-up 6 months
Is the streamlined protocol as safe as the current best practice protocol? The number of symptomatic hypotension requiring hospitalization and hyperkalaemia requiring hospitalization.
Maximum follow-up 6 months
Change in NT-pro BNP
Time Frame: 6 months
Do patients on the streamlined protocol have a greater decrease in N-terminal pro-B-type natriuretic peptide (NT-pro BNP) levels 6 months after the initial optimization appointment?
6 months
Symptomatic change
Time Frame: 6 months

5. Do patients on the streamlined protocol have a greater reduction in symptoms at 6 months after the initial optimization appointment? Use of the Kansas City Cardiomyopathy Questionaire score***.

***Kansas City Cardiomyopathy Questionaire score assesses health status of patients with heart failure via four domains: Physical Limitation, Symptom Frequency, Quality of Life and Social Limitations. Each domain provides an individual score from 0 to 100, with 0 denoting the worst and 100 the best possible health status.
6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

The Queen Elizabeth Hospital King's Lynn NHS Foundation Trust

Collaborators

Novartis Pharmaceuticals

Investigators

  • Principal Investigator: Rudolf M Duehmke, BSc MBBS PhD, The Queen Elizabeth Hospital King's Lynn NHS Foundation Trust

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 17, 2022

Primary Completion (Actual)

January 7, 2024

Study Completion (Actual)

January 7, 2024

Study Registration Dates

First Submitted

August 19, 2021

First Submitted That Met QC Criteria

August 19, 2021

First Posted (Actual)

August 25, 2021

Study Record Updates

Last Update Posted (Actual)

March 25, 2025

Last Update Submitted That Met QC Criteria

March 9, 2025

Last Verified

February 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Qehkl

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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