Evidence mapPaperPMID 39881316Full record

Trial reportBMC medicine2025

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.

Xiexiong Zhao, Tao Liu, Qiong Yang, Guoping Yang, Xingli Li, Xiaohong Tang, Jingle Li, Zhongshu Liang, Anying Li, Lixiong Zeng and 12 more

Registry-linked trialAbstract readRandomized Controlled Trial
In one paragraph

Trial report in BMC medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05377203 (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), which is not on this map. Cited by 3 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed, 1 pooled it
field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT05377203 phase4completednot on this map

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

TypeinterventionalSponsorThe Third Xiangya Hospital of Central South UniversityRan2022 to 2023Enrolled90ConditionsHypertension, Arterial HypertensionArmsQuadruple combination of half doses therapy→Dual combination of standard dose therapy, Dual combination of standard dose therapy→ Quadruple combination of half doses therapy
3 · Its place in the literature

Who cites it

3 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Review
  3. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

22 authors.

Xiexiong ZhaoDepartment of Cardiology, The Third Xiangya Hospital of Central South University, Yuelu District, 138 Tongzipo Road, Changsha, 410013, Hunan, China.ORCID http://orcid.org/0000-0002-2570-7390
Tao LiuDepartment of Cardiology, The Third Xiangya Hospital of Central South University, Yuelu District, 138 Tongzipo Road, Changsha, 410013, Hunan, China.ORCID http://orcid.org/0000-0002-0776-2900
Qiong YangDepartment of Cardiology, The Third Xiangya Hospital of Central South University, Yuelu District, 138 Tongzipo Road, Changsha, 410013, Hunan, China.
Guoping YangCenter of Clinical Pharmacology, The Third Xiangya Hospital of Central South University, Changsha, China.
Xingli LiDepartment of Epidemiology, XiangYa School of Public Health, Changsha, China.
Xiaohong TangDepartment of Cardiology, The Third Xiangya Hospital of Central South University, Yuelu District, 138 Tongzipo Road, Changsha, 410013, Hunan, China.ORCID http://orcid.org/0000-0003-4240-3468
Jingle LiDepartment of Cardiology, The Third Xiangya Hospital of Central South University, Yuelu District, 138 Tongzipo Road, Changsha, 410013, Hunan, China.
Zhongshu LiangDepartment of Cardiology, The Third Xiangya Hospital of Central South University, Yuelu District, 138 Tongzipo Road, Changsha, 410013, Hunan, China.
Anying LiDepartment of Cardiology, The Third Xiangya Hospital of Central South University, Yuelu District, 138 Tongzipo Road, Changsha, 410013, Hunan, China.
Lixiong ZengDepartment of Cardiology, The Third Xiangya Hospital of Central South University, Yuelu District, 138 Tongzipo Road, Changsha, 410013, Hunan, China.
Juan WenDepartment of Cardiology, The Third Xiangya Hospital of Central South University, Yuelu District, 138 Tongzipo Road, Changsha, 410013, Hunan, China.
Xiaoyan WangDepartment of Cardiology, The Third Xiangya Hospital of Central South University, Yuelu District, 138 Tongzipo Road, Changsha, 410013, Hunan, China.
Liping PengDepartment of Cardiology, The Third Xiangya Hospital of Central South University, Yuelu District, 138 Tongzipo Road, Changsha, 410013, Hunan, China.
Wenjuan WangDepartment of Cardiology, The Third Xiangya Hospital of Central South University, Yuelu District, 138 Tongzipo Road, Changsha, 410013, Hunan, China.
Jingjing CaiDepartment of Cardiology, The Third Xiangya Hospital of Central South University, Yuelu District, 138 Tongzipo Road, Changsha, 410013, Hunan, China.
Ye ChenDepartment of Cardiology, The Third Xiangya Hospital of Central South University, Yuelu District, 138 Tongzipo Road, Changsha, 410013, Hunan, China.
Miao HuangDepartment of Cardiology, The Third Xiangya Hospital of Central South University, Yuelu District, 138 Tongzipo Road, Changsha, 410013, Hunan, China.
Ruixuan LiDepartment of Cardiology, The Third Xiangya Hospital of Central South University, Yuelu District, 138 Tongzipo Road, Changsha, 410013, Hunan, China.
Ru FuDepartment of Cardiology, The Third Xiangya Hospital of Central South University, Yuelu District, 138 Tongzipo Road, Changsha, 410013, Hunan, China.
Lin ZhaoDepartment of Cardiology, The Third Xiangya Hospital of Central South University, Yuelu District, 138 Tongzipo Road, Changsha, 410013, Hunan, China.
Xiaogang Li *Department of Cardiology, The Third Xiangya Hospital of Central South University, Yuelu District, 138 Tongzipo Road, Changsha, 410013, Hunan, China.
Weihong Jiang *Department of Cardiology, The Third Xiangya Hospital of Central South University, Yuelu District, 138 Tongzipo Road, Changsha, 410013, Hunan, China. jiangweihongdoc@163.com.ORCID http://orcid.org/0000-0001-8369-9694

Funding

the Key Research and Development program of Hunan Province 2022SK2029the National Natural Science Foundation of China Projects 81800271
6 · The paper itself

Abstract

backgroundGuidelines recognized dual combination in initial antihypertensive therapy. Studies found that low-dose quadruple combination were superior to monotherapy. However, whether low-dose quadruple therapy is better than dual combination is unknown.

methodsA randomized blinded crossover trial was conducted to compare the efficacy and safety of low-dose quadruple antihypertensives (irbesartan 75 mg + metoprolol 23.75 mg + amlodipine 2.5 mg + indapamide 1.25 mg) with standard-dose dual antihypertensives (irbesartan 150 mg + amlodipine 5 mg), both in a single pill, in the initial treatment of patients with mild to moderate hypertension. Patients were randomly assigned in a 1:1 ratio to two crossover sequences. Each sequence received four-weeks of either half-dose quadruple antihypertensives or standard-dose dual antihypertensives, followed by a two-week washout and crossover for four-weeks. Participants and researchers were blinded. The main outcomes were the reduction of blood pressure and safety outcomes. Analyses were per intention to treat.

resultsA total of 90 eligible participants were randomized between July 13, 2022, and April 20, 2023. The mean age was 43.88 years (SD 10.31), and 25.6% were women. The mean baseline 24-h blood pressure was 145.59/93.84 mm Hg. Compared to the standard-dose dual treatment, the half-dose quadruple treatment resulted in a further reduction in mean 24-h blood pressure by 4.72/4.17 mm Hg (P < 0.001 for both systolic and diastolic blood pressure), mean daytime blood pressure by 5.52/4.73 mm Hg (P < 0.001 for both), mean nighttime blood pressure by 2.37/2.25 mm Hg (P = 0.034 and 0.014, respectively), and mean office blood pressure by 2.91/1.73 mm Hg (P < 0.001 and 0.014, respectively). Apart from significant increases of fasting blood glucose (P = 0.029) and blood uric acid (P < 0.001) in the half-dose quadruple group, no other adverse events or changes in laboratory values differed significantly between the two treatments.

conclusionsInitiating treatment with half-dose quadruple combination therapy was more effective in lowering blood pressure than standard-dose dual therapy. The safety of half-dose quadruple therapy was comparable.

trial registrationClinicalTrials.gov Identifier: NCT05377203.

Indexed as

AmlodipineAntihypertensive AgentsHypertensionMetoprololAdultAgedBlood PressureCapsulesCross-Over StudiesDrug Therapy, CombinationFemaleHumansIndapamideMaleMiddle AgedTreatment OutcomeAmlodipineAntihypertensive AgentsCapsulesIndapamideMetoprololAntihypertensiveHypertensionLow-dose combinationRandomized controlled trial

Identifiers

PMID39881316
PMCPMC11780824

What Socratic holds

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LicenceCC BY-NC-ND
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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.