# A double-blind randomized controlled trial to assess the efficacy and safety of a quadruple ultra-low-dose treatment for hypertension (QUARTET USA)

> **NIH NIH R33** · NORTHWESTERN UNIVERSITY · 2021 · $1,104,047

## Abstract

PROJECT SUMMARY/ABSTRACT
 The proposed application will investigate whether initiating treatment with ultra-low-dose quadruple-
combination therapy (LDQT; including irbesartan 37.5 mg, amlodipine 1.25 mg, indapamide 0.625 mg, and
bisoprolol 2.5 mg) will lower automated office blood pressure and 24-hour ambulatory blood pressure at 12
weeks more effectively, and with no increase in side effects, compared to initiating standard dose monotherapy
(irbesartan 150 mg) in adults with raised blood pressure (SBP>140 mmHg or DBP>90 mmHg) and without
cardiovascular disease. Our preliminary data from a short-term (4-week) crossover trial of 18 participants
suggest that LDQT lowers office blood pressure by 22/13 mmHg on average compared with placebo with no
difference in serious adverse events. Effects on 24-hour ambulatory blood pressure were similar.
 We will perform this phase II, single site, randomized controlled trial in a network of federally qualified
health centers in Chicago because this population bears a disproportionate burden of blood pressure related
diseases, and we have previously successfully conducted clinical studies in this population. This new and
simpler treatment paradigm has potential to eliminate blood pressure disparities in this population, which
provides the motivation for this proposal. While we hypothesize this intervention will be easily implemented and
efficacious for all patients and clinicians, we will explore variation in treatment effect by potential moderating
variables, including age, sex, race/ethnicity, and health literacy level. Beyond examining efficacy, we also plan
to assess feasibility of implementing this intervention in a clinical setting by simultaneously evaluating
implementation outcomes of acceptability, preferences, and lessons of LDQT among patients and clinicians.
 Two early stage investigators will lead the study team with relevant, complementary clinical trial experience
in cardiovascular medicine and biostatistics, which provide a strong foundation for this proposal. Our team will
leverage internal and external experience and resources in cardiovascular research, combination drug therapy,
and implementation science to study a novel intervention in a high-burden, low-resource population from a
single site through this phase II trial. We plan to pool the present trial data with that of similar trial conducted in
Australia (led by one of the study team members in this proposal) to examine the robustness and
generalizability of our study results.
Relevance
 This proposal aims to create, evaluate, and demonstrate successful implementation of an ultra-low dose
quadruple combination drug therapy that is simpler, more efficacious, and safer than standard therapy for
patients and their doctors. If successful, then the proposal will lay the framework for a larger multi-site phase III
randomized controlled trial with goal of confirming efficacy and safety in a larger population, with the ultimate
goal of a comple...

## Key facts

- **NIH application ID:** 10021704
- **Project number:** 5R33HL139852-03
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** Jody D. Ciolino
- **Activity code:** R33 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $1,104,047
- **Award type:** 5
- **Project period:** 2018-06-15 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10021704

## Citation

> US National Institutes of Health, RePORTER application 10021704, A double-blind randomized controlled trial to assess the efficacy and safety of a quadruple ultra-low-dose treatment for hypertension (QUARTET USA) (5R33HL139852-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10021704. Licensed CC0.

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