A Double Blind Randomized Controlled Trial to Assess the Efficacy and Safety of a Quadruple Ultra-low-dose Treatment for Hypertension (QUARTET USA)
Trial Snapshot
- Phase
- Phase 2
- Status
- Completed
- Enrollment
- 62
- Locations
- 2
- Primary Endpoint
- Change in Mean Systolic Blood Pressure
Study Overview
Brief Summary
To investigate, in a double-blind randomized controlled trial, whether initiating treatment with ultra-low-dose quadruple-combination therapy ("LDQT") will lower office blood pressure more effectively, and with fewer side effects, compared to initiating standard dose monotherapy as per current guidelines in patients with hypertension.
Primary hypothesis: A combination pill comprising four types of blood pressure lowering medications, each at one-quarter standard doses, will lower office blood pressure more effectively than initiating patients with standard dose monotherapy as per contemporary clinical practice guideline recommendations.
Detailed Description
This trial will investigate whether initiating treatment with ultra-low-dose quadruple-combination therapy (LDQT; including candesartan 2 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 (candesartan 8 mg) in adults with raised blood pressure (SBP>130 mmHg or DBP>80 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.
The investigators 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 the investigators have previously successfully conducted clinical studies in this population.
While the investigators hypothesize this intervention will be easily implemented and efficacious for all patients and clinicians, the investigators will explore variation in treatment effect by potential moderating variables, including age, sex, race/ethnicity, and health literacy level. Beyond examining efficacy, the investigators 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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Adults (≥18 years)
- •Spanish or English speaker.
- •Previous documentation within the past 24 months of hypertension or high blood pressure (SBP 130-179 mmHg or DBP 80-109 mmHg) from general practitioner, pharmacist or health care professional (e.g., medical assistant, physician or nurse).
- •Either: 1) Untreated (automated) clinic SBP 140-179 or DBP 90-109 mmHg in the last 12 weeks, OR 2) Monotherapy with clinic SBP 130-159 or DBP 85-99 mmHg in the last 12 weeks.
- •Either: 1) Treatment naïve, OR 2) Currently not on treatment (not take in last 4 weeks), OR 3) Currently taking 1 BP lowering drug (ACE, ARB, CCB, thiazide- or thiazide-like diuretic, BB, MRA, alpha blocker) at any dose.
- •Research grade blood pressure measurement (baseline mean) SBP>= 115 mmHg and DBP >= 60 mmHg
Exclusion Criteria
- •Known contraindication to candesartan, amlodipine, indapamide or bisoprolol.
- •Previous diagnosis of coronary artery disease, stroke, or heart failure.
- •Presence of significant proteinuria (based on 3+ proteinuria via spot urinalysis or >300mg/dL of proteinuria based on random urinary albumin-to-creatinine ratio testing of 300 mg/g)
- •Evidence of secondary cause of hypertension e.g., renal artery stenosis; significant renal impairment (eGFR <50 ml/min/1.73 m2), raised serum potassium (above lab normal limit of 5.5 mEq/L).
- •Women who are pregnant, breast feeding or of childbearing potential and are not using and do not plan to continue using medically acceptable form of contraception throughout the study (pharmacological or barrier methods).
- •Concomitant illness, physical impairment or mental condition which in the opinion of the study team / primary care physician could interfere with the conduct of the study including outcome assessments.
- •Participation in a concurrent interventional medical investigation or pharmacologic clinical trial. Patients in observational, natural history or epidemiological studies not involving an intervention are eligible.
- •Participant's responsible primary care or other responsible physician believes it is not appropriate for participant to switch current monotherapy.
- •Inability or unwillingness to provide written informed consent.
- •Unable to complete study procedures.
Arms & Interventions
QUARTET LDQT
Patients randomized to the intervention arm will take a once daily ultra-low-dose quadruple combination therapy (QUARTET LDQT). The LDQT is an overencapsulated combination pill comprising four types of blood pressure lowering medications each at ¼ standard doses. QUARTET includes candesartan 2mg, amlodipine besylate 1.25mg, indapamide 0.625mg, and bisoprolol 2.5mg. The individual components are currently approved and marketed within the United States.
Intervention: QUARTET LDQT (Drug)
Candesartan
Patients randomized to the comparison arm will take a once daily 8mg candesartan.
Intervention: Candesartan (Drug)
Outcomes
Primary Outcomes
Change in Mean Systolic Blood Pressure
Time Frame: 12 weeks
Mean change (from baseline) in automated office systolic blood pressure adjusted for baseline values.
Secondary Outcomes
- Mean Diastolic Blood Pressure(6 weeks)
- Proportion of Patients With Hypertension Control(6 and 12 weeks)
- Proportion of Patients With Adverse Event Free Hypertension Control(12 weeks)
- Mean Systolic Blood Pressure(6 weeks)
- Change in Mean Diastolic Blood Pressure(6 weeks)
- Health-related Quality of Life(12 weeks)
- Change in Mean Systolic Blood Pressure(6 weeks)
- Number of Patients Requiring Step up Treatment(6 weeks)
- Medication Adherence(12 weeks)
Investigators
Mark Huffman
Professor of Medicine and Global Health Center Co-Director
Washington University School of Medicine