Efficacy and Safety of a Quadruple Ultra-low-dose Treatment for Hypertension

Hypertension Clinical Trial

— QUARTET USA  

Official title:

A Double Blind Randomized Controlled Trial to Assess the Efficacy and Safety of a Quadruple Ultra-low-dose Treatment for Hypertension (QUARTET USA)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03640312
• Other study ID #: 202203097-STU00205834
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: August 30, 2019
• Est. completion date: July 31, 2024

Study information

• Verified date: September 2023
• Source: Washington University School of Medicine
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 62
• Est. completion date: July 31, 2024
• Est. primary completion date: May 31, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Hypertension

Intervention

Drug:
• QUARTET LDQT
Ultra-low-dose combination therapy comprising four different blood pressure lowering drugs at 1/4 dosages. Taken once daily for 12 weeks.
• Candesartan
Standard monotherapy of 8mg candesartan. Taken once daily for 12 weeks.

Locations

Country	Name	City	State
United States	ACCESS Martin T. Russo Family Health Center	Bloomingdale	Illinois
United States	Ashland Family Health Center	Chicago	Illinois

Sponsors (3)

Lead Sponsor	Collaborator
Washington University School of Medicine	ACCESS Community Health Network, University of Sydney

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Percentage of Participants With Serious Adverse Events (SAEs)	Percentage of participants with any Serious Adverse Events (SAE) according to Good Clinical Practice definition: adverse events that result in death, are life threatening, require hospitalization or prolong existing hospitalization, result in persistent disability, result in congenital anomaly or birth defect, or unimportant medical event that requires intervention to prevent any of the above.	12 weeks
Other	Percentage of Participants With Potentially Related Adverse Events	Percentage of participants with occurrence of any potentially related adverse event (pre-specified as in study procedures). Defined as: At least possibly related to study drug.	12 weeks
Other	Rate of Adverse Events of Special Interest	Rate of pre-specified adverse events that are known side effects of active ingredients at the participant level.	12 weeks
Other	Mean Change in Serum Potassium	Mean change (from baseline) in continuous serum potassium.	12 weeks
Other	Mean Change in Serum Sodium	Mean change (from baseline) in continuous serum sodium.	12 weeks
Other	Mean Change in Blood Urea Nitrogen	Mean change (from baseline) in continuous blood urea nitrogen.	12 weeks
Other	Mean Change in Serum Creatinine	Mean change in continuous serum creatinine.	12 weeks
Primary	Change in Mean Systolic Blood Pressure	Mean change (from baseline) in automated office systolic blood pressure adjusted for baseline values.	12 weeks
Secondary	Mean Systolic Blood Pressure	Mean automated office systolic blood pressure adjusted for baseline values.	6 weeks
Secondary	Change in Mean Diastolic Blood Pressure	Mean change (from baseline) in automated office diastolic blood pressure adjusted for baseline values.	6 weeks
Secondary	Mean Diastolic Blood Pressure	Mean automated office diastolic blood pressure adjusted for baseline values.	6 weeks
Secondary	Proportion of Patients With Hypertension Control	Proportion of patients with hypertension control (percent with SBP < 130 mmHg and DBP <80 mmHg).	6 and 12 weeks
Secondary	Number of Patients Requiring Step up Treatment	Number of patients requiring step-up treatment.	6 weeks
Secondary	Proportion of Patients With Adverse Event Free Hypertension Control	Proportion of patients with adverse event free hypertension control (percent with SBP < 130 mmHg and DBP <80 mmHg).	12 weeks
Secondary	Medication Adherence	Medication adherence defined by objective pill counts	12 weeks
Secondary	Health-related Quality of Life	Mean change (from baseline) in health-related quality of life using Patient-Reported Outcomes Measurement Information System (PROMIS) Global Health instrument. PROMIS Global Health is a gauge of general health-care related quality of life. Possible PROMIS Global Physical Health and Global Mental Health scores range from 0-20, with 20 indicating best possible state of health. Raw scores are converted to T-scores to compare to a standardized population. A PROMIS T-score of 50 represents the mean of the population (SD = 10). Higher values here also indicate better health. A positive change in T score, as reported in this outcome measure, would represent an improvement in Global Physical Health or Global Mental Health at 12 weeks compared to baseline.	12 weeks
Secondary	Change in Mean Systolic Blood Pressure	Mean change (from baseline) in automated office systolic blood pressure adjusted for baseline values.	6 weeks