Low-dose Quadruple Combination Therapy in Patients With Hypertension

NCT05377203 | Completed Phase 4 DMC

• 2 other identifiers: R22023MR-43-23-020339
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 1

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.

Conditions

Hypertension; Arterial Hypertension

Keywords

hypertension; combination therapy; low dose; randomized controlled trial; crossover design

Outcome Measures

Primary Outcomes (1)

• Mean systolic blood pressure of 24-hour

  The reduction of mean systolic blood pressure of 24-hour in Ambulatory Blood Pressure Monitoring (ABPM) after 4 weeks of medication (from baseline).

  Four weeks

Secondary Outcomes (7)

• Mean systolic blood pressure of daytime and night

  Four weeks

• Mean diastolic blood pressure of 24-hour, daytime and night

  Four weeks

• Morning blood pressure surge

  Four weeks

• Office blood pressure

  Four weeks

• Home blood pressure

  Four weeks

Other Outcomes (14)

• Percentage of participants with severe adverse events (SAE)

  Four weeks

• Percentage of participants with side effects

  Four weeks

• Rate of relevant side effects

  Four weeks

Study Arms (2)

Group A

EXPERIMENTAL

Quadruple combination of half doses therapy for 4 weeks→Wash out for 2 weeks →Dual combination of standard dose therapy for 4 weeks.

Drug: Quadruple combination of half doses therapy→Dual combination of standard dose therapy

Group B

EXPERIMENTAL

Dual combination of standard dose therapy for 4 weeks→Wash out for 2 weeks →Quadruple combination of half doses therapy for 4 weeks.

Drug: Dual combination of standard dose therapy→ Quadruple combination of half doses therapy

Interventions

Quadruple combination of half doses therapy→Dual combination of standard dose therapy DRUG

Quadruple combination of half doses therapy: a single capsule containing quadruple combination of half doses of blood pressure medicines (amlodipine besylate tablet 2.5mg, amlodipine besylate tablet simulator 2.5mg, irbesartan tablets 75mg, irbesartan tablets simulator 75mg, metoprolol succinate sustained-release tablets 23.75mg, indapamide tablets 1.25mg), take orally, one capsule once a day. Dual combination of standard dose therapy: a single capsule containing dual combination of standard dose of blood pressure medicines (amlodipine besylate tablets 2.5mg×2, irbesartan tablets 75mg×2, metoprolol succinate sustained-release tablets simulator 23.75mg, indapamide tablets simulator 1.25mg), take orally, one capsule once a day.

Group A

Dual combination of standard dose therapy→ Quadruple combination of half doses therapy DRUG

Dual combination of standard dose therapy: a single capsule containing dual combination of standard dose of blood pressure medicines (amlodipine besylate tablets 2.5mg×2, irbesartan tablets 75mg×2, metoprolol succinate sustained-release tablets simulator 23.75mg, indapamide tablets simulator 1.25mg), take orally, one capsule once a day. Quadruple combination of half doses therapy: a single capsule containing quadruple combination of half doses of blood pressure medicines (amlodipine besylate tablet 2.5mg, amlodipine besylate tablet simulator 2.5mg, irbesartan tablets 75mg, irbesartan tablets simulator 75mg, metoprolol succinate sustained-release tablets 23.75mg, indapamide tablets 1.25mg), take orally, one capsule once a day.

Group B

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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;

Sponsors & Collaborators

• The Third Xiangya Hospital of Central South University: lead

Study Sites (1)

The Third Xiangya Hospital of Central South University

Changsha, Hunan, 410013, China

Location

Related Publications (9)

• 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.

  PMID: 31080465 BACKGROUND

• 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.

  PMID: 32370572 BACKGROUND

• Lu J, Lu Y, Wang X, Li X, Linderman GC, Wu C, Cheng X, Mu L, Zhang H, Liu J, Su M, Zhao H, Spatz ES, Spertus JA, Masoudi FA, Krumholz HM, Jiang L. Prevalence, awareness, treatment, and control of hypertension in China: data from 1.7 million adults in a population-based screening study (China PEACE Million Persons Project). Lancet. 2017 Dec 9;390(10112):2549-2558. doi: 10.1016/S0140-6736(17)32478-9. Epub 2017 Nov 5.

  PMID: 29102084 BACKGROUND

• Chow CK, Gupta R. Blood pressure control: a challenge to global health systems. Lancet. 2019 Aug 24;394(10199):613-615. doi: 10.1016/S0140-6736(19)31293-0. Epub 2019 Jul 18. No abstract available.

  PMID: 31327567 BACKGROUND

• 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.

  PMID: 33190560 BACKGROUND

• 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.

  PMID: 34458905 BACKGROUND

• Zhao X, Liu T, Yang Q, Yang G, Li X, Tang X, Li J, Liang Z, Li A, Zeng L, Wen J, Wang X, Peng L, Wang W, Cai J, Chen Y, Huang M, Li R, Fu R, Zhao L, Li X, Jiang W. Initial treatment with a single capsule containing half-dose quadruple therapy vs standard-dose dual therapy in hypertensive patients (QUADUAL): a randomized, blinded, crossover trial. BMC Med. 2025 Jan 29;23(1):56. doi: 10.1186/s12916-025-03892-8.

  PMID: 39881316 DERIVED

• Zhao X, Li X, Liu T, Yang G, Chen Y, Huang M, Zhao L, Li X, Jiang W. Initial treatment with a single capsule containing half-dose quadruple therapy versus standard-dose dual therapy in hypertensive patients (QUADUAL): statistical analysis plan for a randomized, blinded, crossover trial. Trials. 2024 Jan 13;25(1):45. doi: 10.1186/s13063-023-07803-1.

  PMID: 38218924 DERIVED

• Zhao X, Chen Y, Yang G, Li X, Tang X, Yang Q, Peng L, Li J, Liang Z, Li A, Wang W, Huang M, Liu T, Li X, Jiang W. Initial treatment with a single capsule containing half-dose quadruple therapy vs standard-dose dual therapy in hypertensive patients (QUADUAL): Study protocol for a randomized, blinded, crossover trial. Am Heart J. 2023 Oct;264:10-19. doi: 10.1016/j.ahj.2023.05.019. Epub 2023 Jun 4.

  PMID: 37276913 DERIVED

MeSH Terms

Conditions

Hypertension

Interventions

Therapeutics

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases

Study Officials

• Weihong Jiang, Doctor

  The Third Xiangya Hospital of Central South University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Persons except who make masking plan and conduct medicine coding, are all masked.
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 2×2 crossover design

Study Record Dates

• First Submitted: May 6, 2022
• First Posted: May 17, 2022
• Study Start: July 13, 2022
• Primary Completion: July 4, 2023
• Study Completion: July 4, 2023
• Last Updated: July 18, 2023

Record last verified: 2023-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, CSR
• Time Frame: When study protocol and clinical study report are accepted to publish, they will be available.

Locations

CN (1)