Clinical trial NCT05377203: Low-dose Quadruple Combination Therapy in Patients With Hypertension
Official title: Initial Treatment With a Single Capsule Containing Quadruple Combination of Half Doses of Blood Pressure Medicines Versus Standard Dose Dual Therapy in Patients With Hypertension: A Single-center, Randomized, Double-blind, Crossover Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Hypertension
Arterial Hypertension
Keywords: hypertension
combination therapy
low dose
randomized controlled trial
crossover design
Lead sponsor: The Third Xiangya Hospital of Central South University
Sponsor class: OTHER
First posted: 2022-05-17
Enrollment: 90
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: 2×2 crossover design
Primary purpose: TREATMENT

Brief summary: This study aims to compare the antihypertensive effect of initial treatment with a single capsule containing quadruple combination of half-dose of blood pressure medicines or standard dose dual combination in patients with hypertension.

Detailed description: This is a single-center, randomized, double-blind, crossover trial, planning to enroll 90 patients with grade 1 and 2 hypertension in the Third Xiangya Hospital of Central South University. The participants will be divided into two groups randomly and treated with half-dose quadruple antihypertensive therapy (irbesartan 75mg+ metoprolol 23.75mg+ amlodipine 2.5mg+ indapamide 1.25mg) or with full-dose dual antihypertensive therapy (irbesartan 150mg+ amlodipine 5mg) for four weeks. After washing out with placebo for two weeks, the participants of the two groups will exchange their medication and be treated for another four weeks. The changes of blood pressure (including 24-hour ambulatory blood pressure, office blood pressure, and home blood pressure) and related adverse effects of the two groups will be compared.

Eligibility criteria: Inclusion Criteria:

* Age ≥18 years, \< 80 years old；
* Have never taken antihypertensive medications or have not taken antihypertensive medications in the past 1 month；
* Patients with hypertension (meet the following two parameters to avoid white coat hypertension):a. Office Blood Pressure: systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg measured 3 times on different days;b. ABPM: average blood pressure of 24h ≥130/80 mmHg; Or average blood pressure of daytime ≥135/85 mmHg; Or average blood pressure of night ≥120/70 mmHg;
* Participate voluntarily and sign written informed consent.

Exclusion Criteria:

* Confirmed or highly suspected secondary hypertension, such as primary aldosteronism, Cushing's syndrome, pheochromocytoma or paraganglioma, aortic constriction, renal arterial stenosis, renal hypertension, hyperthyroidism, etc.;
* Severe hypertension: systolic blood pressure ≥180 mmHg and/or diastolic blood pressure ≥110 mmHg in the consulting room or hypertensive emergency or urgency at the time of visit;
* Differences in blood pressure of both upper limbs ≥20/10mmHg;
* Allergic to irbesartan, metoprolol, amlodipine, indapamide and sulfonamides;
* Cannot swallow tablets;
* Pregnant and lactating women;
* Possible reproductive needs during the trial;
* Uncorrected electrolyte disorder (serum potassium \> 5.5mmol/L or \< 3.5mmol/L, serum sodium \< 135mmol/L);
* Severe organ dysfunction, including impaired renal function (GFR \< 60mL /min/1.73m\^2), impaired liver function (aspartate aminotransferase or alanine aminotransferase ≥ 3 times the upper limit of normal), NYHF classification class IV for cardiac function;
* Comorbidities lead to inaccurate blood pressure measurement, such as arrhythmia, etc.;
* Comorbidities result in the prohibition or caution of the experimental drugs, such as: aortic stenosis, mitral valve stenosis, hypertrophic obstructive cardiomyopathy, bilateral renal artery stenosis or renal artery stenosis with solitary kidney, gout, hyperuricemia (serum uric acid \>420μmol/L in men or 360μmol/L in women), acute coronary syndrome, sick sinus syndrome, degree II-III of atrioventricular block, severe peripheral vascular disease with high risk of gangrene, history or family history of angioedema;
* Comorbidities affect the absorption, distribution, metabolism and excretion of the experimental drugs such as: gastrointestinal resection, gastrointestinal bypass surgery, sympathetic nerve resection or other operations, active inflammatory bowel disease, malignant tumors undergoing or planning to undergo radiotherapy or chemotherapy or targeted therapy, etc.;
* Medications in use or about to be used may lead to the prohibition or caution of experimental drugs: such as ACEI, Aliskiren, lithium agent, etc.;
* Medications in use or about to be used will interfere the results of this study, such as: hormones, Sacubitril valsartan and spironolactone for patients with chronic heart failure, Dapagliflozin and Liraglutide for patients with diabetes, and long-term medication for patients with chronic coronary heart disease, etc.;
* Not appropriate for antihypertensive therapies of this trial evaluated by physician;
* Participating in other clinical research that may affect the conduct of this study.

Primary outcomes:
measure: Mean systolic blood pressure of 24-hour
timeFrame: Four weeks
Secondary outcomes:
measure: Mean systolic blood pressure of daytime and night
timeFrame: Four weeks
measure: Mean diastolic blood pressure of 24-hour, daytime and night
timeFrame: Four weeks
measure: Morning blood pressure surge
timeFrame: Four weeks
measure: Office blood pressure
timeFrame: Four weeks
measure: Home blood pressure
timeFrame: Four weeks
measure: Heart rate
timeFrame: Four weeks
measure: Controlled rate of blood pressure
timeFrame: Four weeks
Other outcomes:
measure: Percentage of participants with severe adverse events (SAE)
timeFrame: Four weeks
measure: Percentage of participants with side effects
timeFrame: Four weeks
measure: Rate of relevant side effects
timeFrame: Four weeks
measure: Mean change in serum potassium
timeFrame: Four weeks
measure: Mean change in serum sodium
timeFrame: Four weeks
measure: Mean change in blood urea nitrogen
timeFrame: Four weeks
measure: Mean change in serum creatinine
timeFrame: Four weeks
measure: Mean change in serum uric acid
timeFrame: Four weeks
measure: Mean change in serum glutamic-oxalacetic transaminase
timeFrame: Four weeks
measure: Mean change in serum glutamic-pyruvic transaminase
timeFrame: Four weeks
measure: Mean change in serum bilirubin
timeFrame: Four weeks
measure: Mean change in blood glucose
timeFrame: Four weeks
measure: Mean change in urinary protein
timeFrame: Four weeks
measure: Change in electrocardiogram QT Interval
timeFrame: Four weeks
Locations:
city: Changsha
country: China
facility: The Third Xiangya Hospital of Central South University
state: Hunan
Study officials:
affiliation: The Third Xiangya Hospital of Central South University
name: Weihong Jiang, Doctor
role: PRINCIPAL_INVESTIGATOR
References:
citation: Joint Committee for Guideline Revision. 2018 Chinese Guidelines for Prevention and Treatment of Hypertension-A report of the Revision Committee of Chinese Guidelines for Prevention and Treatment of Hypertension. J Geriatr Cardiol. 2019 Mar;16(3):182-241. doi: 10.11909/j.issn.1671-5411.2019.03.014. No abstract available.
citation: Unger T, Borghi C, Charchar F, Khan NA, Poulter NR, Prabhakaran D, Ramirez A, Schlaich M, Stergiou GS, Tomaszewski M, Wainford RD, Williams B, Schutte AE. 2020 International Society of Hypertension Global Hypertension Practice Guidelines. Hypertension. 2020 Jun;75(6):1334-1357. doi: 10.1161/HYPERTENSIONAHA.120.15026. Epub 2020 May 6. No abstract available.
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citation: An J, Luong T, Qian L, Wei R, Liu R, Muntner P, Brettler J, Jaffe MG, Moran AE, Reynolds K. Treatment Patterns and Blood Pressure Control With Initiation of Combination Versus Monotherapy Antihypertensive Regimens. Hypertension. 2021 Jan;77(1):103-113. doi: 10.1161/HYPERTENSIONAHA.120.15462. Epub 2020 Nov 16.
citation: Visseren FLJ, Mach F, Smulders YM, Carballo D, Koskinas KC, Back M, Benetos A, Biffi A, Boavida JM, Capodanno D, Cosyns B, Crawford C, Davos CH, Desormais I, Di Angelantonio E, Franco OH, Halvorsen S, Hobbs FDR, Hollander M, Jankowska EA, Michal M, Sacco S, Sattar N, Tokgozoglu L, Tonstad S, Tsioufis KP, van Dis I, van Gelder IC, Wanner C, Williams B; ESC National Cardiac Societies; ESC Scientific Document Group. 2021 ESC Guidelines on cardiovascular disease prevention in clinical practice. Eur Heart J. 2021 Sep 7;42(34):3227-3337. doi: 10.1093/eurheartj/ehab484. No abstract available.