Efficacy of a Streamlined Heart Failure Optimization Protocol (SHORT)

The Queen Elizabeth Hospital King's Lynn NHS Foundation Trust

Status: Completed

Conditions: Heart Failure with Reduced Ejection Fraction; Chronic Heart Failure

Treatments: Other: Streamlined protocol; Other: Standard Protocol

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT05021419

Qehkl

Details and patient eligibility

About

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

Full 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.

Enrollment: 60 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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60 participants in 2 patient groups

Standard Arm

Active Comparator group

Description:

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

Treatment:

Other: Standard Protocol

Streamlined protocol arm

Experimental group

Description:

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.

Treatment:

Other: Streamlined protocol