Low-dose Quadruple Combination Therapy in Patients With Hypertension (QUADUAL)

July 16, 2023 updated by: The Third Xiangya Hospital of Central South University

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

90

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
    • Hunan
      • Changsha, Hunan, China, 410013
        • The Third Xiangya Hospital of Central South University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years to 76 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Group A
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

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.
Experimental: Group B
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

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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Mean systolic blood pressure of 24-hour
Time Frame: Four weeks
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Mean systolic blood pressure of daytime and night
Time Frame: Four weeks
The reduction of mean systolic blood pressure of daytime and night in ABPM after 4 weeks of medication (from baseline).
Four weeks
Mean diastolic blood pressure of 24-hour, daytime and night
Time Frame: Four weeks
The reduction of mean diastolic blood pressure of 24-hour, daytime and night in ABPM after 4 weeks of medication (from baseline).
Four weeks
Morning blood pressure surge
Time Frame: Four weeks
The change of morning blood pressure surge in ABPM after 4 weeks of medication (from baseline).
Four weeks
Office blood pressure
Time Frame: Four weeks
The reduction of office blood pressure after 4 weeks of medication (from baseline).
Four weeks
Home blood pressure
Time Frame: Four weeks
The reduction of home blood pressure after 4 weeks of medication (from baseline).
Four weeks
Heart rate
Time Frame: Four weeks
The change in heart rate after 4 weeks of medication (from baseline).
Four weeks
Controlled rate of blood pressure
Time Frame: Four weeks
Controlled rate of blood pressure after 4 weeks of medication (from baseline).
Four weeks

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of participants with severe adverse events (SAE)
Time Frame: Four weeks
Percentage of participants with any SAE according to Good Clinical Practice definition.
Four weeks
Percentage of participants with side effects
Time Frame: Four weeks
Percentage of participants with occurrence of any potentially relevant side effect (pre-specified as in study protocol).
Four weeks
Rate of relevant side effects
Time Frame: Four weeks
Rate of relevant side effects (pre-specified as in study protocol) at the participant level.
Four weeks
Mean change in serum potassium
Time Frame: Four weeks
Mean change (from baseline) in serum potassium after 4 weeks of medication.
Four weeks
Mean change in serum sodium
Time Frame: Four weeks
Mean change (from baseline) in serum sodium after 4 weeks of medication.
Four weeks
Mean change in blood urea nitrogen
Time Frame: Four weeks
Mean change (from baseline) in blood urea nitrogen after 4 weeks of medication.
Four weeks
Mean change in serum creatinine
Time Frame: Four weeks
Mean change (from baseline) in serum creatinine after 4 weeks of medication.
Four weeks
Mean change in serum uric acid
Time Frame: Four weeks
Mean change (from baseline) in serum uric acid after 4 weeks of medication.
Four weeks
Mean change in serum glutamic-oxalacetic transaminase
Time Frame: Four weeks
Mean change (from baseline) in serum glutamic-oxalacetic transaminase after 4 weeks of medication.
Four weeks
Mean change in serum glutamic-pyruvic transaminase
Time Frame: Four weeks
Mean change (from baseline) in serum glutamic-pyruvic transaminase after 4 weeks of medication.
Four weeks
Mean change in serum bilirubin
Time Frame: Four weeks
Mean change (from baseline) in serum bilirubin (total and direct bilirubin) after 4 weeks of medication.
Four weeks
Mean change in blood glucose
Time Frame: Four weeks
Mean change (from baseline) in blood glucose after 4 weeks of medication.
Four weeks
Mean change in urinary protein
Time Frame: Four weeks
Mean change (from baseline) in urinary protein (-, +, ++, +++) after 4 weeks of medication.
Four weeks
Change in electrocardiogram QT Interval
Time Frame: Four weeks
Change (from baseline) in electrocardiogram QT Interval after 4 weeks of medication.
Four weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

The Third Xiangya Hospital of Central South University

Investigators

  • Principal Investigator: Weihong Jiang, Doctor, The Third Xiangya Hospital of Central South University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 13, 2022

Primary Completion (Actual)

July 4, 2023

Study Completion (Actual)

July 4, 2023

Study Registration Dates

First Submitted

May 6, 2022

First Submitted That Met QC Criteria

May 11, 2022

First Posted (Actual)

May 17, 2022

Study Record Updates

Last Update Posted (Actual)

July 18, 2023

Last Update Submitted That Met QC Criteria

July 16, 2023

Last Verified

July 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • R22023
  • MR-43-23-020339 (Registry Identifier: Medical Research Registration & Information System of China)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Study protocol and clinical study report will be shared by publishing way.

IPD Sharing Time Frame

When study protocol and clinical study report are accepted to publish, they will be available.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • CSR

Study Data/Documents

  1. Study Protocol
    Information identifier: PMID: 37276913

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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