UMIN-CTR Clinical Trial

Basic information
Public title	Effects of switching from sacubitril/valsartan to valsartan alone on plasma levels of natriuretic peptides and cardiac remodeling in heart failure with reduced ejection fraction
Acronym	SAVASAVA Study
Scientific Title	Effects of switching from sacubitril/valsartan to valsartan alone on plasma levels of natriuretic peptides and cardiac remodeling in heart failure with reduced ejection fraction
Scientific Title:Acronym	SAVASAVA Study
Region	Japan

Condition
Condition	Patients with heart failure who finished the PARALLEL-HF trial
Classification by specialty	Cardiology Adult
Classification by malignancy	Others
Genomic information	NO

Objectives
Narrative objectives1	To examine the impact of switching from angiotensin receptor-neprilysin inhibitor (ARNI) to angiotensin-receptor blocker (ARB) on plasma levels of natriuretic peptides and myocardial remodeling.
Basic objectives2	Safety
Basic objectives -Others
Trial characteristics_1
Trial characteristics_2
Developmental phase

Assessment
Primary outcomes	The primary endpoint was percent change (%Change) from baseline to week 24 in plasma A-, B-, and N-terminal pro-B-type natriuretic peptide (ANP, BNP, and NT-proBNP) levels.
Key secondary outcomes	The second endpoint was the change in echocardiographic parameters related to myocardial remodeling from the baseline to week 24.

Base
Study type	Observational

Study design
Basic design
Randomization
Randomization unit
Blinding
Control
Stratification
Dynamic allocation
Institution consideration
Blocking
Concealment

Intervention
No. of arms
Purpose of intervention
Type of intervention
Interventions/Control_1
Interventions/Control_2
Interventions/Control_3
Interventions/Control_4
Interventions/Control_5
Interventions/Control_6
Interventions/Control_7
Interventions/Control_8
Interventions/Control_9
Interventions/Control_10

Eligibility
Age-lower limit	20 years-old <
Age-upper limit	80 years-old >=
Gender	Male and Female
Key inclusion criteria	patients with chronic HF in our hospital participated in the PARALLEL-HF trial
Key exclusion criteria	Patients who did not consent to participate
Target sample size	11

Research contact person
Name of lead principal investigator	1st name Akihiro Middle name Last name Nakamura
Organization	Iwate Prefectural Central Hospital
Division name	Department of Cardiology
Zip code	020-0066
Address	1-4-1, Ueda, Morioka, Iwate
TEL	019-653-1151
Email	Akihironakamura0223@msn.com

Public contact
Name of contact person	1st name Akihiro Middle name Last name Nakamura
Organization	Iwate Prefectural Central Hospital
Division name	Department of Cardiology
Zip code	020-0066
Address	1-4-1, Ueda, Morioka, Iwate
TEL	019-653-1151
Homepage URL
Email	Akihironakamura0223@msn.com

Sponsor
Institute	Department of Cardiology, Iwate Prefectural Central Hospital
Institute
Department

Funding Source
Organization	Iwate Prefectural Central Hospital
Organization
Division
Category of Funding Organization	Local Government
Nationality of Funding Organization

Other related organizations
Co-sponsor
Name of secondary funder(s)

IRB Contact (For public release)
Organization	Iwate Prefectural Central Hospital
Address	1-4-4, Ueda, Morioka, Iwate
Tel	019-653-1151
Email	yoshiko-tanaka@pref.iwate.jp

Secondary IDs
Secondary IDs	NO
Study ID_1
Org. issuing International ID_1
Study ID_2
Org. issuing International ID_2
IND to MHLW

Institutions
Institutions

Other administrative information
Date of disclosure of the study information	2022 Year 08 Month 05 Day

Related information
URL releasing protocol	http://chuo-hp.jp/oshirase/chikentop/
Publication of results	Unpublished

Result
URL related to results and publications	http://chuo-hp.jp/oshirase/chikentop/
Number of participants that the trial has enrolled	11
Results	The %Change in ANP and NT-proBNP levels was significantly greater in the ARB-switch group than that in the ARNI-continue group, wheras that in BNP levels was not significantly different between the ARNI-continue and ARB-switch group. In the ARB-switch group, there was a significant increase from the baseline to week 24 in left ventricular (LV) end-systolic volume (p = 0.043) and LV peak-systolic wall stress (p = 0.012), and a trend toward a decrease in LV ejection fraction (p = 0.080).
Results date posted	2022 Year 08 Month 05 Day
Results Delayed	Delay expected
Results Delay Reason	No accept for any journals
Date of the first journal publication of results	2022 Year 12 Month 01 Day
Baseline Characteristics	The patient age of the ARB-switch group was significantly smaller than that of the ARNI-continue group (p = 0.028). No significant differences in sex, body mass index, body surface area, heart rate, BP, risk factors, biochemical data, and medications were not found between the two groups.
Participant flow	Despite the recommendation to continue the ARNI treatment, six of 11 patients desired the change from the treatment with ARNI to that with ARB because of medical costs or two weeks visit after the study. The remaining five patients wanted to continue the treatment with ARNI. After completed the core study between December 2020 and January 2021, two groups were enrolled in this study: five patients who requested the continuous treatment with ARNI: sacubitril valsartan of 400 mg/day (ARNI continue group);and six patients who requested the treatment with ARB: valsartan of 160 mg/day (ARB switch group).
Adverse events	In all patients, the ARNI or ARB treatment was not changed or discontinued during the study period. No patients were given additional medications for HF such as sodium-glucose cotransporter-2 inhibitors. Unplanned hospitalization due to worsening HF or other cardiovascular events was not observed in the both groups.
Outcome measures	Switching from ARNI to ARB may worsen HF due to returning to myocardial remodeling induced by a sustained decline in ANP levels.
Plan to share IPD	None
IPD sharing Plan description	None

Progress
Recruitment status	Completed
Date of protocol fixation	2020 Year 12 Month 01 Day
Date of IRB	2020 Year 12 Month 03 Day
Anticipated trial start date	2021 Year 01 Month 05 Day
Last follow-up date	2021 Year 07 Month 30 Day
Date of closure to data entry	2021 Year 08 Month 31 Day
Date trial data considered complete	2021 Year 09 Month 01 Day
Date analysis concluded	2022 Year 10 Month 01 Day

Other
Other related information	The follow-up visits were conducted at 4, 12, and 24 weeks

Management information
Registered date	2022 Year 08 Month 05 Day
Last modified on	2022 Year 08 Month 05 Day

Link to view the page
URL(English)	https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000055376