Heart Failure with Reduced Ejection FractionSHORTNCT05021419
Efficacy of a Streamlined Heart Failure Optimization Protocol
A study testing Streamlined protocol and Standard Protocol in people with Heart Failure with Reduced Ejection Fraction and Chronic Heart Failure, run by The Queen Elizabeth Hospital King's Lynn NHS Foundation Trust at 1 site in United Kingdom.
Trial summary
The SHORT trial compares the current standard optimization protocol to a shortened protocol in a randomized control trial. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Heart Failure with Reduced Ejection Fraction, Chronic Heart Failure
- What is being tested?
- Streamlined protocol and Standard Protocol
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 17 Jul 2022to 7 Jan 2024
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
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- 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 locations and contacts
1 site in 1 country.
United Kingdom1 site
Queen Elizabeth Hospital King's Lynn
Kings Lynn, Norfolk, PE30 4ET
About this study
Official title: 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.
Read the 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.
- Being tested
- Streamlined protocol, Standard Protocol
- Keywords
- Medication Sequencing, Optimization
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Streamlined protocolOther
A streamlined drug protocol for optimizing heart failure medication
Standard ProtocolOther
Current standard optimization protocol as per NICE and ESC
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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. Receives: Other: Streamlined protocol |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Maximum follow-up 6 months
Secondary outcomes (6)
Degree of optimization reached
- 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.
Measured: Maximum follow-up 6 months
Number of appointments required
Do patients on the streamlined protocol require fewer appointments to reach the point of optimization?
Measured: Maximum follow-up 6 months
Number of Complications
Is the streamlined protocol as safe as the current best practice protocol? The number of symptomatic hypotension requiring hospitalization and hyperkalaemia requiring hospitalization.
Measured: Maximum follow-up 6 months
Change in NT-pro BNP
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?
Measured: 6 months
Symptomatic change
- 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.
Measured: 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)?
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Aug 2021
- Study start17 Jul 2022
- Primary completion7 Jan 2024
- Study completion7 Jan 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Heart Failure with Reduced Ejection FractionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 60 participants (actual)
Sponsor and investigators
- Lead sponsor
- The Queen Elizabeth Hospital King's Lynn NHS Foundation Trust
- Sponsor type
- University, hospital or other
- Collaborators
- Novartis Pharmaceuticals
- Responsible party
- Sponsor
- Investigators
- Rudolf M Duehmke, BSc MBBS PhD, Principal investigator, The Queen Elizabeth Hospital King's Lynn NHS Foundation Trust
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05021419
- Sponsor's protocol ID
- Qehkl
- Acronym
- SHORT
- Status last verified
- Feb 2025
- First submitted
- 19 Aug 2021
- Last updated
- 12 Mar 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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/
PubMed 30645061Ponikowski 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.
PubMed 27206819McMurray 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.
PubMed 31535829McMurray 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.
PubMed 33378214
Study at a glance
From the registry record, last updated by the sponsor on 12 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy of a Streamlined Heart Failure Optimisation PRoTocol for Patients with Severely Impaired Left Ventricular Systolic Function, a Randomised Controlled Trial (SHORT Trial)
- ClinicalTrials.gov ID
- NCT05021419
- Acronym / sponsor ID
- SHORT / Qehkl
- Keywords
- Medication Sequencing, Optimization
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 60 participants (actual)
- Lead sponsor
- The Queen Elizabeth Hospital King's Lynn NHS Foundation TrustUniversity, hospital or other
- Collaborators
- Novartis Pharmaceuticals
- Study start
- 17 Jul 2022 (actual)
- Primary completion
- 7 Jan 2024 (actual)
- Study completion
- 7 Jan 2024 (actual)
- First posted
- 25 Aug 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The SHORT trial compares the current standard optimization protocol to a shortened protocol in a randomized control trial.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Standard Arm | Active comparator | Other: Standard ProtocolBoth 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 |
| Streamlined protocol arm | Experimental | Other: Streamlined protocolPatients 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (12 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Streamlined protocolA streamlined drug protocol for optimizing heart failure medication | Other | Streamlined protocol arm |
| Standard ProtocolCurrent standard optimization protocol as per NICE and ESC | Other | Standard Arm |
Primary outcome
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.
6 secondary outcomes
Degree of optimization reached
Time frame: Maximum follow-up 6 months
Number of appointments required
Time frame: Maximum follow-up 6 months
Number of Complications
Time frame: Maximum follow-up 6 months
Change in NT-pro BNP
Time frame: 6 months
Symptomatic change
Time frame: 6 months
Composite of cardiovascular death and worsening heart failure
Time frame: 6 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Mar 2025.
- Background: PubMed 30645061National 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/
- Background: PubMed 27206819Ponikowski 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.
- Background: PubMed 31535829McMurray 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.
- Background: PubMed 33378214McMurray 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Rudolf M Duehmke, BSc MBBS PhD principal investigator
The Queen Elizabeth Hospital King's Lynn NHS Foundation Trust
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Streamlined protocol and Standard Protocol in people with Heart Failure with Reduced Ejection Fraction and Chronic Heart Failure, run by The Queen Elizabeth Hospital King's Lynn NHS Foundation Trust at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Time to point of optimization (time frame: Maximum follow-up 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05021419, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Mar 2025; AzTrials last refreshed its copy on 27 Oct 2026.