Efficacy of a Streamlined Heart Failure Optimization Protocol

NCT05021419 | Completed

• 1 other identifier: Qehkl
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Heart Failure with Reduced Ejection Fraction; Chronic Heart Failure

Keywords

Medication Sequencing; Optimization

Outcome Measures

Primary Outcomes (1)

• 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, BP, or raised serum potassium or serum Creatinine.

  Maximum follow-up 6 months

Secondary Outcomes (6)

• Degree of optimization reached

  Maximum follow-up 6 months

• Number of appointments required

  Maximum follow-up 6 months

• Number of Complications

  Maximum follow-up 6 months

• Change in NT-pro BNP

  6 months

• Symptomatic change

  6 months

Study Arms (2)

Standard Arm

ACTIVE COMPARATOR

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

Streamlined protocol arm

EXPERIMENTAL

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

Interventions

Streamlined protocol OTHER

A streamlined drug protocol for optimizing heart failure medication

Streamlined protocol arm

Standard Protocol OTHER

Current standard optimization protocol as per NICE and ESC

Standard Arm

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• The Queen Elizabeth Hospital King's Lynn NHS Foundation Trust: lead
• Novartis Pharmaceuticals: collaborator

Study Sites (1)

Queen Elizabeth Hospital King's Lynn

Kings Lynn, Norfolk, PE30 4ET, United Kingdom

Location

Related Publications (4)

• National Guideline Centre (UK). Chronic Heart Failure in Adults: Diagnosis and Management. London: National Institute for Health and Care Excellence (NICE); 2018 Sep. Available from http://www.ncbi.nlm.nih.gov/books/NBK536075/

  PMID: 30645061 BACKGROUND

• Ponikowski P, Voors AA, Anker SD, Bueno H, Cleland JGF, Coats AJS, Falk V, Gonzalez-Juanatey JR, Harjola VP, Jankowska EA, Jessup M, Linde C, Nihoyannopoulos P, Parissis JT, Pieske B, Riley JP, Rosano GMC, Ruilope LM, Ruschitzka F, Rutten FH, van der Meer P; ESC Scientific Document Group. 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC)Developed with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur Heart J. 2016 Jul 14;37(27):2129-2200. doi: 10.1093/eurheartj/ehw128. Epub 2016 May 20. No abstract available.

  PMID: 27206819 BACKGROUND

• McMurray JJV, Solomon SD, Inzucchi SE, Kober L, Kosiborod MN, Martinez FA, Ponikowski P, Sabatine MS, Anand IS, Belohlavek J, Bohm M, Chiang CE, Chopra VK, de Boer RA, Desai AS, Diez M, Drozdz J, Dukat A, Ge J, Howlett JG, Katova T, Kitakaze M, Ljungman CEA, Merkely B, Nicolau JC, O'Meara E, Petrie MC, Vinh PN, Schou M, Tereshchenko S, Verma S, Held C, DeMets DL, Docherty KF, Jhund PS, Bengtsson O, Sjostrand M, Langkilde AM; DAPA-HF Trial Committees and Investigators. Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction. N Engl J Med. 2019 Nov 21;381(21):1995-2008. doi: 10.1056/NEJMoa1911303. Epub 2019 Sep 19.

  PMID: 31535829 BACKGROUND

• McMurray JJV, Packer M. How Should We Sequence the Treatments for Heart Failure and a Reduced Ejection Fraction?: A Redefinition of Evidence-Based Medicine. Circulation. 2021 Mar 2;143(9):875-877. doi: 10.1161/CIRCULATIONAHA.120.052926. Epub 2020 Dec 30. No abstract available.

  PMID: 33378214 BACKGROUND

MeSH Terms

Interventions

AIEOP acute lymphoblastic leukemia protocol

Study Officials

• Rudolf M Duehmke, BSc MBBS PhD

  The Queen Elizabeth Hospital King's Lynn NHS Foundation Trust

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 19, 2021
• First Posted: August 25, 2021
• Study Start: July 17, 2022
• Primary Completion: January 7, 2024
• Study Completion: January 7, 2024
• Last Updated: March 12, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)