Hemodialysis ComplicationESARHD-HFNCT04458285
Efficacy and Safety of Sacubitril/Valsartan in Maintenance Hemodialysis Patients With Heart Failure
A study testing Sacubitril / Valsartan Oral Tablet [Entresto] and Valsartan 80mg Tablet in people with Hemodialysis Complication and Heart Failure, run by Guangdong Provincial People's Hospital at 1 site in China.
Trial summary
Sacubitril/valsartan reduces the risk of cardiovascular mortality among patients with heart failure with reduced ejection fraction, and has been recently indicated as a new treatment option with a strong level of recommendation (class I, level of evidence B) in the main international guidelines. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Hemodialysis Complication, Heart Failure
- What is being tested?
- Sacubitril / Valsartan Oral Tablet [Entresto] and Valsartan 80mg Tablet
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 118 participants
- Where
- 1 siteChina
- Study dates
- 1 Jan 2020to 31 Dec 2020
- 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 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Written informed consent obtained before any study assessment is performed.
- End stage renal disease (ESRD) patients (eGFR<15ml/min/1.73m² as measured by the Chronic Kidney Disease Epidemiology Collaboration formula at screening) who have been receiving hemodialysis 3 times a week for at least 12 weeks before registration.
- Chronic heart failure (NYHA class ≥ II) with reduced ejection fraction, defined as known LVEF ≤ 50%.
- Mean sitting systolic blood pressure(msSBP)≥110 mmHg.
- Use of angiotensin-converting enzyme inhibitors/angiotensin receptor blocker for at least 2 weeks.
- Good compliance.
Who cannot join
- Acute renal failure with hemodialysis.
- Isolated right heart failure owing to pulmonary disease, primary cause of dyspnea due to noncardiac, non-HF causes such as acute or chronic respiratory disorders.
- Systolic blood pressure lower than 100 mmHg at screening (<95 mmHg at the randomization visit).
- Previous history of intolerance to recommended target doses of angiotensin receptor blockers.
- Significant laboratory abnormalities at screening interfering with assessment of study drug safety or efficacy (such as serum potassium>5.5 or <3.5mmol/L, serum sodium<130mmol/L or alanine aminotransferase or aspartate aminotransferase>2 times the upper limit of the normal range)
- History of hypersensitivity to any of the study drugs or their excipients or to drugs of similar chemical classes.
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- History of angioedema.
- Any medications that have potential for drug-drug interaction with LCZ696 will not be allowed during the study.
- Pregnant female.
- Use of sacubitril/valsartan prior to week-2.
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Guangdong Provincial People's Hospital
Guangzhou, Guangdong, 510080
Shuangxin Liu, Doctor, (+86)13543456446, 13543456446@139.com
Shuangxin Liu, Doctor
About this study
Official title: A Multi-center, Randomized, Open-label, Active-controlled, 12-week Study to Evaluate the Efficacy and Safety of Sacubitril/Valsartan in Maintenance Hemodialysis Patients With Heart Failure
Sacubitril/valsartan reduces the risk of cardiovascular mortality among patients with heart failure with reduced ejection fraction, and has been recently indicated as a new treatment option with a strong level of recommendation (class I, level of evidence B) in the main international guidelines. Cardiovascular disease (CVD) is the most common cause of death in end stage renal disease (ESRD) patients undergoing hemodialysis (HD). Hence, treatments to improve mortality and specifically cardiovascular outcomes in this population are greatly needed. So far, no data available about the efficacy and safety of sacubitril/valsartan in ESRD patients undergoing hemodialysis, although this medication was noted to be effective and comparably well tolerable in those with estimated glomerular filtration rate(eGFR) 20 to 60 mL/min/1.73 m2 in the United Kingdom Heart and Renal Protection-III trial.
The purpose of this open label, randomized controlled study with prospective data collection is to assess the efficacy and safety of sacubitril/valsartan in maintenance hemodialysis patients with heart failure.
- Conditions
- Hemodialysis Complication, Heart Failure
- Being tested
- Sacubitril / Valsartan Oral Tablet [Entresto], Valsartan 80mg Tablet
- Keywords
- Sacubitril/valsartan, valsartan, Hemodialysis, Heart failure
- Medical subject headings
- Heart Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Sacubitril / Valsartan Oral Tablet [Entresto]Drug
Also called LCZ696 100 mg tablet
Patients in experimental group will receive sacubitril/valsartan with the recommended starting dose: 50mg twice daily (if previous ACEI, ensure 36-hour washout period), after 2-4 weeks, the dose will be doubled to the target maintenance dose of 100mg twice daily(if tolerated) for 12 weeks.
Valsartan 80mg TabletDrug
Patients in active comparator group will receive Valsartan with an dose of 80 mg once daily.
| Study group | Role | What they receive |
|---|---|---|
| Sacubitril/valsartan | Experimental | Patients in experimental group will receive sacubitril/valsartan with the recommended starting dose: 50mg twice daily (if previous angiotensin converting enzyme inhibitor(ACEI), ensure 36-hour washout period), after 2-4 weeks, the dose will be doubled to the target maintenance dose of 100mg twice daily(if tolerated) for 12 weeks. Receives: Drug: Sacubitril / Valsartan Oral Tablet [Entresto] |
| Valsartan | Active comparator | Patients in active comparator group will receive Valsartan with an dose of 80 mg once daily. Receives: Drug: Valsartan 80mg Tablet |
What is being measured
The primary outcome is the main question the study is designed to answer.
Left ventricular ejection fraction (LVEF)
Change from baseline in left ventricular ejection fraction (LVEF) between baseline and end of study
Measured: 12 weeks
Secondary outcomes (14)
N terminal pro B type natriuretic peptide (NT-prpBNP)
Blood samples will be collected for analysis of concentration of N terminal pro B type natriuretic peptide (NT-proBNP) every 2 weeks.
Measured: 12 weeks
Left ventricular end diastolic volume (LVEDV)
LVEDV is measured as baseline and after 12 weeks follow-up.
Measured: 12 weeks
Left atrial volume (LAV)
LAV is measured as baseline and after 12 weeks follow-up.
Measured: 12 weeks
The ratio of mitral early diastolic blood flow peak and mitral annulus velocity (E/E')
E/E' is measured as baseline and after 12 weeks follow-up.
Measured: 12 weeks
Pulmonary Artery Pressure
Pulmonary Artery Pressure is measured as baseline and after 12 weeks follow-up.
Measured: 12 weeks
Concentration of high-sensitivity serum troponin T
Blood samples will be collected for analysis of concentration of serum troponin every 4 weeks.
Measured: 12 weeks
NYHA functional classification
NYHA functional classification is assessed from baseline and 12 weeks follow-up.
Measured: 12 weeks
Minnesota Heart Failure Quality of Life Questionnaire (LiHFe)
Change in health status is assessed using the disease-specific Minnesota Heart Failure Quality of Life Questionnaire.
Measured: 12 weeks
Systolic and diastolic blood pressure
Systolic and diastolic blood pressure will be measured every 2 weeks.
Measured: 12 weeks
Concentration of postassium
Blood samples will be collected for analysis of concentration of postassium every 2 weeks.
Measured: 12 weeks
Electrocardiogram(ECG)
ECG QT Interval analysis was performed at baseline and 12 weeks follow-up.
Measured: 12 weeks
Estimated glomerular filtration rate(eGFR)
Change in estimated glomerular filtration rate(eGFR)
Measured: 12 weeks
Incidence of Angioedema
Incidence of Angioedema during the study period 12 weeks.
Measured: 12 weeks
Concentration of alanine aminotransferase or aspartate aminotransferase
Blood samples will be collected for analysis of concentration of alanine aminotransferase or aspartate aminotransferase every 2 weeks.
Measured: 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Jul 2020
- Study start1 Jan 2020
- Primary completion31 Dec 2020 (estimated)
- Study completion31 Dec 2020 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Hemodialysis ComplicationStudies of the same condition, open and under way.
- More trials run by Guangdong Provincial People's HospitalThe sponsor's other registered studies.
- 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
- 118 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Guangdong Provincial People's Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, ShuangXin Liu, Guangdong Provincial People's Hospital
- Investigators
- Shuangxin Liu, Doctor, Principal investigator, Guangdong Provincial People's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04458285
- Sponsor's protocol ID
- 20191025
- Acronym
- ESARHD-HF
- Status last verified
- Jul 2020
- First submitted
- 26 Jun 2020
- Last updated
- 6 Oct 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
McMurray JJ, Packer M, Desai AS, Gong J, Lefkowitz MP, Rizkala AR, Rouleau JL, Shi VC, Solomon SD, Swedberg K, Zile MR; PARADIGM-HF Investigators and Committees. Angiotensin-neprilysin inhibition versus enalapril in heart failure. N Engl J Med. 2014 Sep 11;371(11):993-1004. doi: 10.1056/NEJMoa1409077. Epub 2014 Aug 30.
PubMed 25176015Haynes R, Judge PK, Staplin N, Herrington WG, Storey BC, Bethel A, Bowman L, Brunskill N, Cockwell P, Hill M, Kalra PA, McMurray JJV, Taal M, Wheeler DC, Landray MJ, Baigent C. Effects of Sacubitril/Valsartan Versus Irbesartan in Patients With Chronic Kidney Disease. Circulation. 2018 Oct 9;138(15):1505-1514. doi: 10.1161/CIRCULATIONAHA.118.034818.
PubMed 30002098Velazquez EJ, Morrow DA, DeVore AD, Duffy CI, Ambrosy AP, McCague K, Rocha R, Braunwald E; PIONEER-HF Investigators. Angiotensin-Neprilysin Inhibition in Acute Decompensated Heart Failure. N Engl J Med. 2019 Feb 7;380(6):539-548. doi: 10.1056/NEJMoa1812851. Epub 2018 Nov 11.
PubMed 30415601
Study at a glance
From the registry record, last updated by the sponsor on 6 Oct 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multi-center, Randomized, Open-label, Active-controlled, 12-week Study to Evaluate the Efficacy and Safety of Sacubitril/Valsartan in Maintenance Hemodialysis Patients With Heart Failure
- ClinicalTrials.gov ID
- NCT04458285
- Acronym / sponsor ID
- ESARHD-HF / 20191025
- Conditions
- Hemodialysis Complication, Heart Failure
- Keywords
- Sacubitril/valsartan, valsartan, Hemodialysis, Heart failure
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 118 participants (estimated)
- Lead sponsor
- Guangdong Provincial People's HospitalUniversity, hospital or other
- Study start
- 1 Jan 2020 (actual)
- Primary completion
- 31 Dec 2020 (estimated)
- Study completion
- 31 Dec 2020 (estimated)
- First posted
- 7 Jul 2020 (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.
Sacubitril/valsartan reduces the risk of cardiovascular mortality among patients with heart failure with reduced ejection fraction, and has been recently indicated as a new treatment option with a strong level of recommendation (class I, level of evidence B) in the main international guidelines. Cardiovascular disease (CVD) is the most common cause of death in end stage renal disease (ESRD) patients undergoing hemodialysis (HD). Hence, treatments to improve mortality and specifically cardiovascular outcomes in this population are greatly needed. So far, no data available about the efficacy and safety of sacubitril/valsartan in ESRD patients undergoing hemodialysis, although this medication was noted to be effective and comparably well tolerable in those with estimated glomerular filtration rate(eGFR) 20 to 60 mL/min/1.73 m2 in the United Kingdom Heart and Renal Protection-III trial.
The purpose of this open label, randomized controlled study with prospective data collection is to assess the efficacy and safety of sacubitril/valsartan in maintenance hemodialysis patients with heart failure.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Sacubitril/valsartan | Experimental | Drug: Sacubitril / Valsartan Oral Tablet [Entresto]Patients in experimental group will receive sacubitril/valsartan with the recommended starting dose: 50mg twice daily (if previous angiotensin converting enzyme inhibitor(ACEI), ensure 36-hour washout period), after 2-4 weeks, the dose will be doubled to the target maintenance dose of 100mg twice daily(if tolerated) for 12 weeks. |
| Valsartan | Active comparator | Drug: Valsartan 80mg TabletPatients in active comparator group will receive Valsartan with an dose of 80 mg once daily. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Written informed consent obtained before any study assessment is performed.
- End stage renal disease (ESRD) patients (eGFR<15ml/min/1.73m² as measured by the Chronic Kidney Disease Epidemiology Collaboration formula at screening) who have been receiving hemodialysis 3 times a week for at least 12 weeks before registration.
- Chronic heart failure (NYHA class ≥ II) with reduced ejection fraction, defined as known LVEF ≤ 50%.
- Mean sitting systolic blood pressure(msSBP)≥110 mmHg.
- Use of angiotensin-converting enzyme inhibitors/angiotensin receptor blocker for at least 2 weeks.
Key exclusion criteria (10 listed)
- Acute renal failure with hemodialysis.
- Isolated right heart failure owing to pulmonary disease, primary cause of dyspnea due to noncardiac, non-HF causes such as acute or chronic respiratory disorders.
- Systolic blood pressure lower than 100 mmHg at screening (<95 mmHg at the randomization visit).
- Previous history of intolerance to recommended target doses of angiotensin receptor blockers.
- Significant laboratory abnormalities at screening interfering with assessment of study drug safety or efficacy (such as serum potassium>5.5 or <3.5mmol/L, serum sodium<130mmol/L or alanine aminotransferase or aspartate aminotransferase>2 times the upper limit of the normal range)
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 |
|---|---|---|
| Sacubitril / Valsartan Oral Tablet [Entresto]Also: LCZ696 100 mg tabletPatients in experimental group will receive sacubitril/valsartan with the recommended starting dose: 50mg twice daily (if previous ACEI, ensure 36-hour washout period), after 2-4 weeks, the dose will be doubled to the target maintenance dose of 100mg twice daily(if tolerated) for 12 weeks. | Drug | Sacubitril/valsartan |
| Valsartan 80mg TabletPatients in active comparator group will receive Valsartan with an dose of 80 mg once daily. | Drug | Valsartan |
Primary outcome
Left ventricular ejection fraction (LVEF)
Time frame: 12 weeks
Change from baseline in left ventricular ejection fraction (LVEF) between baseline and end of study
14 secondary outcomes
N terminal pro B type natriuretic peptide (NT-prpBNP)
Time frame: 12 weeks
Left ventricular end diastolic volume (LVEDV)
Time frame: 12 weeks
Left atrial volume (LAV)
Time frame: 12 weeks
The ratio of mitral early diastolic blood flow peak and mitral annulus velocity (E/E')
Time frame: 12 weeks
Pulmonary Artery Pressure
Time frame: 12 weeks
Concentration of high-sensitivity serum troponin T
Time frame: 12 weeks
NYHA functional classification
Time frame: 12 weeks
Minnesota Heart Failure Quality of Life Questionnaire (LiHFe)
Time frame: 12 weeks
Systolic and diastolic blood pressure
Time frame: 12 weeks
Concentration of postassium
Time frame: 12 weeks
Electrocardiogram(ECG)
Time frame: 12 weeks
Estimated glomerular filtration rate(eGFR)
Time frame: 12 weeks
Incidence of Angioedema
Time frame: 12 weeks
Concentration of alanine aminotransferase or aspartate aminotransferase
Time frame: 12 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Oct 2020.
- Background: PubMed 25176015McMurray JJ, Packer M, Desai AS, Gong J, Lefkowitz MP, Rizkala AR, Rouleau JL, Shi VC, Solomon SD, Swedberg K, Zile MR; PARADIGM-HF Investigators and Committees. Angiotensin-neprilysin inhibition versus enalapril in heart failure. N Engl J Med. 2014 Sep 11;371(11):993-1004. doi: 10.1056/NEJMoa1409077. Epub 2014 Aug 30.
- Background: PubMed 30002098Haynes R, Judge PK, Staplin N, Herrington WG, Storey BC, Bethel A, Bowman L, Brunskill N, Cockwell P, Hill M, Kalra PA, McMurray JJV, Taal M, Wheeler DC, Landray MJ, Baigent C. Effects of Sacubitril/Valsartan Versus Irbesartan in Patients With Chronic Kidney Disease. Circulation. 2018 Oct 9;138(15):1505-1514. doi: 10.1161/CIRCULATIONAHA.118.034818.
- Background: PubMed 30415601Velazquez EJ, Morrow DA, DeVore AD, Duffy CI, Ambrosy AP, McCague K, Rocha R, Braunwald E; PIONEER-HF Investigators. Angiotensin-Neprilysin Inhibition in Acute Decompensated Heart Failure. N Engl J Med. 2019 Feb 7;380(6):539-548. doi: 10.1056/NEJMoa1812851. Epub 2018 Nov 11.
- 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.
Shuangxin Liu, Doctor principal investigator
Guangdong Provincial People's Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Sacubitril / Valsartan Oral Tablet [Entresto] and Valsartan 80mg Tablet in people with Hemodialysis Complication and Heart Failure, run by Guangdong Provincial People's Hospital at 1 site in China.
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 6 inclusion and 10 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: status not confirmed, as of the sponsor's last update on 6 Oct 2020. 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 China. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Faye Jiang, Doctor ((+86)020-83525210, gdphgcp@gdph.org.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Left ventricular ejection fraction (LVEF) (time frame: 12 weeks). 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 NCT04458285, which also lists 3 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 6 Oct 2020.