Efficacy of a Streamlined Heart Failure Optimization Protocol

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

Detailed Description
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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.

Official Title
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Efficacy of a Streamlined Heart Failure Optimisation pRoTocol for Patients With Severely Impaired Left Ventricular Systolic Function, a Randomised Controlled Trial (SHORT Trial).

Conditions
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Heart Failure With Reduced Ejection Fraction, Chronic Heart Failure

Intervention / Treatment
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* Other: Streamlined protocol
* Other: Standard Protocol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Ejection fraction of less than 35% Increased NT-pro BNP levels > 600 pg per milliliter or ≥400 pg per milliliter if they had been hospitalized for heart failure within the previous 12 months. Patients with atrial fibrillation or atrial flutter on baseline electrocardiography were required to have an NT-proBNP level of at least 900 pg per milliliter, regardless of their history of hospitalization for heart failure. Exclusion Criteria: 1. Systolic BP of less than 100 mmHg on 2 consecutive measurements 2. eGFR less than 30 ml/min/1.73m2 3. Type 1 diabetes mellitus 4. 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 5. Uncorrected primary valvular disease 6. Active malignancy treatment at time of visit 1 7. 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 8. Women who are pregnant or breastfeeding -

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Standard Arm<br>Active Comparator: Standard Arm Both the current the European society of cardiology guidelines and National Institute of Health and Care Excellence currently advise that chronic stable heart failure patients with severely impaired left ventricular systolic function should initially be optimized as follows: Visit 1: ACEi/ARB and Low Betablocker commenced Visit 2: ACEi/ARB up-titrated; (Beta Blocker up-titrated) Visit 3: ACEi/ARB up-titrated; (Beta Blocker up-titrated) Visit 4: Switch ACEi/ARB to Entresto 100mg Visit 5: Modify Entresto dose to 200mg Visit 6: MRA Added Visit 7: MRA up-titrated Visit 8: SGLT2i started | Other: Standard Protocol<br>* Current standard optimization protocol as per NICE and ESC<br>|
| Experimental: Streamlined protocol arm<br>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 100 mg bd started Visit 2: MRA Added if renal function and potassium levels permit (Betablocker increased if BP and pulse rate permit) Visit 3: MRA up-titrated if BP and renal function and potassium levels permit (Betablocker increased if BP and pulse rate permit) Visit 4+: Betablocker increased if BP and pulse rate permit. Further visits may be required to facilitate a gentle up-titration of betablockers. | Other: Streamlined protocol<br>* A streamlined drug protocol for optimizing heart failure medication<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to point of optimization | 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, blood pressure, or raised serum potassium or serum Creatinine. | Maximum follow-up 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Degree of optimization reached | 1. Do patients on the streamlined protocol reach a greater degree of optimization **? ** degree of optimization defined as the average percentage of the target doses reached across the four heart failure medication drug groups at the point of optimization | Maximum follow-up 6 months | 
| Number of appointments required | Do patients on the streamlined protocol require fewer appointments to reach the point of optimization? | Maximum follow-up 6 months | 
| Number of Complications | Is the streamlined protocol as safe as the current best practice protocol? Number of symptomatic hypotension requiring hospitalization and Hyperkalaemia requiring hospitalization. | Maximum follow-up 6 months | 
| Change in NT-pro BNP | Do patients on the streamlined protocol have greater decrease in NT-pro BNP levels at 6 months after initial optimization appointment? | 6 months | 
| Symptomatic change | 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. | 6 months | 
| Composite of cardiovascular death and worsening heart failure | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Medication Sequencing, Optimization