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QUADUAL: Low-dose Quadruple Combination Therapy in Patients With Hypertension

Sponsor
The Third Xiangya Hospital of Central South University (Other)
Overall Status
Recruiting
CT.gov ID
NCT05377203
Collaborator
(none)
90
Enrollment
1
Location
2
Arms
12.6
Anticipated Duration (Months)
7.1
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
  • Drug: Quadruple combination of half doses therapy→Dual combination of standard dose therapy
  • Drug: Dual combination of standard dose therapy→ Quadruple combination of half doses therapy
 Phase 4

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 Design

Study Type:
Interventional
Anticipated Enrollment :
90 participants
Allocation:
Randomized
Intervention Model:
Crossover Assignment
Intervention Model Description:
2×2 crossover design2×2 crossover design
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:
Persons except who make masking plan and conduct medicine coding, are all masked.
Primary Purpose:
Treatment
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
Actual Study Start Date :
Jul 13, 2022
Anticipated Primary Completion Date :
Aug 1, 2023
Anticipated Study Completion Date :
Aug 1, 2023

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures

  1. Mean systolic blood pressure of 24-hour [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).

Secondary Outcome Measures

  1. Mean systolic blood pressure of daytime and night [Four weeks]

    The reduction of mean systolic blood pressure of daytime and night in ABPM after 4 weeks of medication (from baseline).

  2. Mean diastolic blood pressure of 24-hour, daytime and night [Four weeks]

    The reduction of mean diastolic blood pressure of 24-hour, daytime and night in ABPM after 4 weeks of medication (from baseline).

  3. Morning blood pressure surge [Four weeks]

    The change of morning blood pressure surge in ABPM after 4 weeks of medication (from baseline).

  4. Office blood pressure [Four weeks]

    The reduction of office blood pressure after 4 weeks of medication (from baseline).

  5. Home blood pressure [Four weeks]

    The reduction of home blood pressure after 4 weeks of medication (from baseline).

  6. Heart rate [Four weeks]

    The change in heart rate after 4 weeks of medication (from baseline).

  7. Controlled rate of blood pressure [Four weeks]

    Controlled rate of blood pressure after 4 weeks of medication (from baseline).

Other Outcome Measures

  1. Percentage of participants with severe adverse events (SAE) [Four weeks]

    Percentage of participants with any SAE according to Good Clinical Practice definition.

  2. Percentage of participants with side effects [Four weeks]

    Percentage of participants with occurrence of any potentially relevant side effect (pre-specified as in study protocol).

  3. Rate of relevant side effects [Four weeks]

    Rate of relevant side effects (pre-specified as in study protocol) at the participant level.

  4. Mean change in serum potassium [Four weeks]

    Mean change (from baseline) in serum potassium after 4 weeks of medication.

  5. Mean change in serum sodium [Four weeks]

    Mean change (from baseline) in serum sodium after 4 weeks of medication.

  6. Mean change in blood urea nitrogen [Four weeks]

    Mean change (from baseline) in blood urea nitrogen after 4 weeks of medication.

  7. Mean change in serum creatinine [Four weeks]

    Mean change (from baseline) in serum creatinine after 4 weeks of medication.

  8. Mean change in serum uric acid [Four weeks]

    Mean change (from baseline) in serum uric acid after 4 weeks of medication.

  9. Mean change in serum glutamic-oxalacetic transaminase [Four weeks]

    Mean change (from baseline) in serum glutamic-oxalacetic transaminase after 4 weeks of medication.

  10. Mean change in serum glutamic-pyruvic transaminase [Four weeks]

    Mean change (from baseline) in serum glutamic-pyruvic transaminase after 4 weeks of medication.

  11. Mean change in serum bilirubin [Four weeks]

    Mean change (from baseline) in serum bilirubin (total and direct bilirubin) after 4 weeks of medication.

  12. Mean change in blood glucose [Four weeks]

    Mean change (from baseline) in blood glucose after 4 weeks of medication.

  13. Mean change in urinary protein [Four weeks]

    Mean change (from baseline) in urinary protein (-, +, ++, +++) after 4 weeks of medication.

  14. Change in electrocardiogram QT Interval [Four weeks]

    Change (from baseline) in electrocardiogram QT Interval after 4 weeks of medication.

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years to 80 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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.

Contacts and Locations

Locations

Site City State Country Postal Code
1 The Third Xiangya Hospital of Central South University Changsha Hunan China 410013

Sponsors and Collaborators

  • The Third Xiangya Hospital of Central South University

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

Responsible Party:
The Third Xiangya Hospital of Central South University
ClinicalTrials.gov Identifier:
NCT05377203
Other Study ID Numbers:
  • R22023
First Posted:
May 17, 2022
Last Update Posted:
Jul 15, 2022
Last Verified:
May 1, 2022
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by The Third Xiangya Hospital of Central South University
hypertension
combination therapy
low dose
randomized controlled trial
crossover design
Additional relevant MeSH terms:
Hypertension

Study Results

No Results Posted as of Jul 15, 2022