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Prospective a multicenter, open-label, parallel group comparative, trial to evaluate the antihypertensive efficacy and safety of Sacubitril/Valsartan and Amlodipine besylate in patients with essential hypertension (PARASOL study)

PARASOL study (PARASOL study)

359

Of 422 screened patients, 359 were randomized. A total of 181 patients were allocated to the sacubitril/valsartan group, and the remaining 178 patients were allocated to the amlodipine group. However, the actual number of patients in each group was 182 and 177, respectively, due to a prescription error. In the sacubitril/valsartan group, 136 (76.0%) were males and 43 (24.0%) were females. In the amlodipine group, 130 (73.9%) were males and 46 (26.1%) were females. The average age was 58.4 in the sacubitril/valsartan group and 58.0 in the amlodipine group. Mean BMI was 25.86 kg/m2 in sacubitril/valsartan group, and 25.53 kg/m2 in amlodipine group. Regarding hypertension grade, 48.6% were grade I, 39.7% were grade II in the sacubitril/valsartan group, 47.2% were grade I, and 40.9% were grade II in the amlodipine group. For nocturnal hypertension type, 63.7% were Dippers, and 35.8% were No-Dippers in the sacubitril/valsartan group, 54.0% were Dippers, and 45.5% were non-dippers in the amlodipine group. The proportion of patients who had a treatment history for hypertension was 73.7% in the sacubitril/valsartan group and 70.5% in the amlodipine group. The mean duration of hypertension was 1632.1 days in the sacubitril/valsartan group and 1564.6 days in the amlodipine group.

Of 359 randomized patients, 349 completed the study treatment, and 10 discontinued it. One patient in the sacubitril/valsartan group discontinued due to an adverse event, dizziness. The remaining six patients in the sacubitril/valsartan group and three patients in the amlodipine group discontinued due to investigators' decisions for reasons other than AEs/patients' reasons.

A total of 21 adverse events (AEs) related to the study were reported in 13 patients (7.1%) in the sacubitril/valsartan group, and 11 AEs were reported in 11 patients (6.2%) in the amlodipine group. A total of 21 AEs related to the test drug were reported in 14 patients (7.7%) in the sacubitril/valsartan group, and 12 AEs related to the control drug were reported in 9 patients (5.1%) in the amlodipine group.

As the primary endpoint analysis, the mean 24-hour SBP reduction in sacubitril/valsartan was confirmed to be non-inferior to that in amlodipine [between-treatment difference -0.62 mmHg (95% confidential interval -3.23 to 1.98; p=0.003 for non-inferiority; independent t-test with non-inferiority margin 3.0 mmHg)]. As for secondary endpoint analysis, no significant differences were observed in changes from baseline in 24-hour SBP, DBP or pulse pressure. No between-treatment differences were observed regarding morning, daytime and nighttime BPs, as well as office BPs. The BP control rates (24-hour BP, office BP and wrist BP) at Week 8 also showed no treatment differences.

This study assessed the efficacy and safety of sacubitril/valsartan versus amlodipine in patients with essential hypertension. The mean change in 24-hour SBP in sacubitril/valsartan was non-inferior to that in amlodipine, and the difference in the incidence of drug-related AEs was not significant. These results suggest that the BP-lowering effect of sacubitril/valsartan is comparable to amlodipine, and there are no marked differences in tolerability between them.

Jan. 31, 2025

Dec. 04, 2024

https://onlinelibrary.wiley.com/doi/10.1111/jch.14938

No

No

https://jrct.mhlw.go.jp/latest-detail/jRCTs051220165

Yamamoto Koichi

Osaka University Hospital

2-15 Yamadaoka, Suita, Osaka

kyamamoto@geriat.med.osaka-u.ac.jp

Yamamoto Koichi

Osaka University Hospital

2-15 Yamadaoka, Suita, Osaka

+81-6-6879-3852

kyamamoto@geriat.med.osaka-u.ac.jp

Complete

Feb. 07, 2023

Interventional

randomized controlled trial

open(masking not used)

active control

parallel assignment

treatment purpose

(1)Patients at the age of 18 to 79 at the time of obtaining consent.
(2)Patients with essential hypertension who are 150-179 mmHg on office systolic blood pressure.
(3)Patients who have not taken antihypertensives for 28 days or more before enrollment.
(4)Subjects of Wrist blood pressure monitors:Patients with a wrist circumference of 13.5-21.5 cm.

(1)Patients who are 110 mmHg or higher on office diastolic blood pressure.
(2)Patients who cannot go to hospital by themselves.
(3)Female patiens who are breastfeeding, pregnant or who may become pregnant.
(4)Patients with a history of angioedema (whether drug-related or not).
(5)Patients with moderate or higher liver dysfunction (Child-Pugh classification B or higher).
(6)Patients with a history of sensitivity to dihydropyridine.
(7)Patients with a diagnosis or history of secondary hypertension (Renal Parenchymal Hypertension, Renovascular Hypertension (unilateral or bilateral renal artery stenosis), Coarctation of the aorta, Primary Aldosteronism, Cushing disease, Pheochromocytoma, Polycystic kidney disease, and Drug-Induced Hypertension, etc.).
(8)Patients with renal disease with eGFR less than 30 diagnosed as G3a or higher in CKD severity classification.
(9)Patients with a diagnosis or history of stroke (including lacunar infarction).
(10)Patients with a serum potassium level of 5.5 mmol/L or higher.
(11)Patients with a diagnosis of white coat hypertension.
(12)Patients who are working night shifts.
(13)Patients with an arm circumference greater than 38 cm.
(14)Patients who are judged by the investigator or subinvestigators to be not suitable for participation in the study due to various other reasons.

Both

essential hypertension

Test drug administration group:
Sacubitril/Valsartan is administered orally once daily after breakfast for 10 weeks.
Control drug administration group:
Amlodipine besylate is administered orally once daily after breakfast for 10 weeks.

Blood pressure change in 24-hour SBP from baseline to Week 8.

(1)Blood pressure change in 24-hour SBP from baseline to Week 8.
(2)Blood pressure change in 24-hour DBP from baseline to Week 8.
(3)Blood pressure change in 24-hour PP from baseline to Week 8.
(4)Blood pressure change in 24-hour SBP/DBP on early morning/daytime/nighttime from baseline to Week 8.
(5)Blood pressure change in office blood pressure (SBP, DBP) from baseline to Week 8.
(6)Achievement rate of antihypertensive target at 8 Weeks of administration.
(7)Blood pressure change in nighttime from baseline to Week 8 using a Wrist blood pressure monitor.
(8)ABPM and Wrist blood pressure monitor, comparison of blood pressure values in each measurement.
(9)Number of adverse events and their frequency.
(10)Blood pressure change in office blood pressure (SBP, DBP) from baseline to Week 4.

+81-6-6210-8296

Jan. 24, 2023

none