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

NCT03640312 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: 202203097-STU00205834
• Study Type: interventional
• Target: 62
• Locations: 1 country
• Sites: 2

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.

Conditions

Hypertension

Keywords

Hypertension; Blood Pressure

Outcome Measures

Primary Outcomes (1)

• Change in Mean Systolic Blood Pressure

  Mean change (from baseline) in automated office systolic blood pressure adjusted for baseline values.

  12 weeks

Secondary Outcomes (9)

• Mean Systolic Blood Pressure

  6 weeks

• Change in Mean Diastolic Blood Pressure

  6 weeks

• Mean Diastolic Blood Pressure

  6 weeks

• Proportion of Patients With Hypertension Control

  6 and 12 weeks

• Number of Patients Requiring Step up Treatment

  6 weeks

Other Outcomes (7)

• Percentage of Participants With Serious Adverse Events (SAEs)

  12 weeks

• Percentage of Participants With Potentially Related Adverse Events

  12 weeks

• Rate of Adverse Events of Special Interest

  12 weeks

Study Arms (2)

QUARTET LDQT

EXPERIMENTAL

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.

Drug: QUARTET LDQT

Candesartan

ACTIVE COMPARATOR

Patients randomized to the comparison arm will take a once daily 8mg candesartan.

Drug: Candesartan

Interventions

QUARTET LDQT DRUG

Ultra-low-dose combination therapy comprising four different blood pressure lowering drugs at 1/4 dosages. Taken once daily for 12 weeks.

QUARTET LDQT

Candesartan DRUG

Standard monotherapy of 8mg candesartan. Taken once daily for 12 weeks.

Candesartan

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Washington University School of Medicine: lead
• ACCESS Community Health Network: collaborator
• University of Sydney: collaborator

Study Sites (2)

ACCESS Martin T. Russo Family Health Center

Bloomingdale, Illinois, 60108, United States

Location

Ashland Family Health Center

Chicago, Illinois, 60609, United States

Location

Related Publications (3)

• Huffman MD, Baldridge AS, Lazar D, Abbas H, Mejia J, Flowers FM, Quintana A, Jackson A, Kandula NR, Lloyd-Jones DM, Persell SD, Khan SS, Paparello JJ, Chopra A, Tripathi P, Vu MH, Chow CK, Ciolino JD. Efficacy and safety of a four-drug, quarter-dose treatment for hypertension: the QUARTET USA randomized trial. Hypertens Res. 2024 Jun;47(6):1668-1677. doi: 10.1038/s41440-024-01658-y. Epub 2024 Apr 8.

  PMID: 38584159 DERIVED

• Sanuade OA, Jacobson TA, Quintana A, Flowers FM, Abbasi H, Vu MH, Baldridge AS, Mejia J, Lazar D, Ciolino JD, Huffman MD, Kandula NR. Process Evaluation of a Double-Blind Randomized Controlled Trial to Assess the Efficacy and Safety of a Quadruple Ultra-Low-Dose Treatment for Hypertension Within a Federally Qualified Health Center Network (QUARTET USA). J Am Heart Assoc. 2024 Jan 2;13(1):e032236. doi: 10.1161/JAHA.123.032236. Epub 2023 Dec 29.

  PMID: 38156601 DERIVED

• Baldridge AS, Huffman MD, Lazar D, Abbas H, Flowers FM, Quintana A, Jackson A, Khan SS, Chopra A, Vu M, Tripathi P, Jacobson T, Sanuade OA, Kandula NR, Persell SD, Paparello JJ, Rosul LL, Mejia J, Lloyd-Jones DM, Chow CK, Ciolino JD. Efficacy and safety of a quadruple ultra-low-dose treatment for hypertension (QUARTET USA): Rationale and design for a randomized controlled trial. Am Heart J. 2022 Dec;254:183-193. doi: 10.1016/j.ahj.2022.09.004. Epub 2022 Sep 15.

  PMID: 36116516 DERIVED

MeSH Terms

Conditions

Hypertension

Interventions

candesartan

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases

Results Point of Contact

• Title: Guhan Iyer
• Organization: Washington University in St. Louis

guhaniyer@wustl.edu

3147479487

Study Officials

• Mark D Huffman, PhD, MD

  Northwestern University Feinberg School of Medicine

  PRINCIPAL INVESTIGATOR

• Jody D Ciolino, PhD

  Overall Study Officials:

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine and Global Health Center Co-Director

Study Record Dates

• First Submitted: August 15, 2018
• First Posted: August 21, 2018
• Study Start: August 30, 2019
• Primary Completion: May 31, 2022
• Study Completion: July 31, 2024
• Last Updated: January 3, 2025
• Results First Posted: September 22, 2023

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: Data will be available within 1 year of study conclusion.
• Access Criteria: Access to study data will be managed through NHLBI BioLINCC

Locations

US (2)