Efficacy and Safety of Sacubitril/Valsartan in Maintenance Hemodialysis Patients With Heart Failure

NCT ID: NCT04458285

Last Updated: 2020-10-06

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 118 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-01-01
• Study Completion Date: 2020-12-31

Brief 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. 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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Sacubitril/valsartan

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.

Group Type: EXPERIMENTAL

Sacubitril / Valsartan Oral Tablet [Entresto]

Intervention Type: DRUG

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

Patients in active comparator group will receive Valsartan with an dose of 80 mg once daily.

Group Type: ACTIVE_COMPARATOR

Valsartan 80mg Tablet

Intervention Type: DRUG

Patients in active comparator group will receive Valsartan with an dose of 80 mg once daily.

Interventions

Sacubitril / Valsartan Oral Tablet [Entresto]

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.

Intervention Type: DRUG

Valsartan 80mg Tablet

Patients in active comparator group will receive Valsartan with an dose of 80 mg once daily.

Intervention Type: DRUG

Other Intervention Names

LCZ696 100 mg tablet

Eligibility Criteria

Inclusion Criteria

• 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.

Exclusion Criteria

• 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.
• 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Guangdong Provincial People's Hospital

OTHER

Sponsor Role: lead

Responsible Party

ShuangXin Liu

Chief Physician

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Shuangxin Liu, Doctor

Role: PRINCIPAL_INVESTIGATOR

Guangdong Provincial People's Hospital

Locations

Guangdong Provincial People's Hospital

Guangzhou, Guangdong, China

Site Status: RECRUITING

Countries

China

Central Contacts

Faye Jiang, Doctor

Role: CONTACT

gdphgcp@gdph.org.cn

(+86)020-83525210

Facility Contacts

Shuangxin Liu, Doctor

Role: primary

13543456446@139.com

(+86)13543456446

References

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.

Reference Type: BACKGROUND

PMID: 25176015 (View on PubMed)

Haynes 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.

Reference Type: BACKGROUND

PMID: 30002098 (View on PubMed)

Velazquez 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.

Reference Type: BACKGROUND

PMID: 30415601 (View on PubMed)

Other Identifiers

20191025

Identifier Type: -

Identifier Source: org_study_id