Efficacy and Safety of a Quadruple Ultra-low-dose Treatment for Hypertension - Evidence Based Medicine on FHIR Implementation Guide v1.0.0-ballot2

Evidence Based Medicine on FHIR Implementation Guide, published by HL7 International / Clinical Decision Support. This guide is not an authorized publication; it is the continuous build for version 1.0.0-ballot2 built by the FHIR (HL7® FHIR® Standard) CI Build. This version is based on the current content of https://github.com/HL7/ebm/ and changes regularly. See the Directory of published versions

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

version: 29; Last updated: 2025-08-18 13:22:42+0000

Profile: StudyRegistryRecord

ResearchStudy Study Registration
activity: Registration submission
actual: true
period: 2018-08-15 --> (ongoing)

ResearchStudy Study Registration
activity: Results submission
actual: true
period: 2023-05-31 --> (ongoing)

ResearchStudy Study Registration
activity: Registration submission Quality Check
actual: true
period: 2018-08-17 --> (ongoing)

ResearchStudy Study Registration
activity: Results submission Quality Check
actual: true
period: 2023-09-20 --> (ongoing)

ResearchStudy Study Registration
activity: Record Verification
actual: true
period: ?? --> 2024-12

ResearchStudy Study Registration
activity: Update submission
actual: true
period: ?? --> 2024-12-16

ResearchStudy Study Registration
activity: Registration posting
actual: true
period: 2018-08-21 --> (ongoing)

ResearchStudy Study Registration
activity: Results posting
actual: true
period: 2023-09-22 --> (ongoing)

ResearchStudy Study Registration
activity: Primary outcome data collection
actual: true
period: ?? --> 2022-05-31

ResearchStudy Study Registration
activity: Update posting
actual: true
period: ?? --> 2025-01-03

Artifact Author: Computable Publishing®: ClinicalTrials.gov-to-FEvIR Converter:

ArtifactPublicationStatus: Active

url: https://fevir.net/resources/ResearchStudy/367879

identifier: FEvIR Object Identifier/367879, https://clinicaltrials.gov/NCT03640312 (use: official, ), 202203097-STU00205834, FEvIR Linking Identifier/NCT03640312 FHIR Transform

name: NCT03640312_FHIR_Transform

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

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

label
type: Acronym
value: QUARTET USA

citeAs:

Efficacy and Safety of a Quadruple Ultra-low-dose Treatment for Hypertension [Database Entry: FHIR ResearchStudy Resource]. Contributors: Computable Publishing®: ClinicalTrials.gov-to-FEvIR Converter [Authors/Creators]. In: Fast Evidence Interoperability Resources (FEvIR) Platform, FOI 367879. Revised 2025-08-18. Available at: https://fevir.net/resources/ResearchStudy/367879. Computable resource at: https://fevir.net/resources/ResearchStudy/367879#json.

relatesTo
type: Transforms
target: https://clinicaltrials.gov/api/v2/studies/NCT03640312?format=json

relatesTo
type: Transformed With
target: null @ https://fevir.net/resources/Project/29885

relatesTo
type: Cites
target: 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.

relatesTo
type: Documentation
target: application/pdf @ https://cdn.clinicaltrials.gov/large-docs/12/NCT03640312/Prot_001.pdf

relatesTo
type: Documentation
target: application/pdf @ https://cdn.clinicaltrials.gov/large-docs/12/NCT03640312/SAP_002.pdf

relatesTo
type: Documentation
target: application/pdf @ https://cdn.clinicaltrials.gov/large-docs/12/NCT03640312/ICF_000.pdf

status: Active

primaryPurposeType: Treatment

phase: Phase 2

studyDesign: Design Masking: Quadruple, Blinding of study participants, Blinding of intervention providers, Blinding of data analysts, Blinding of outcome assessors, randomized assignment, Parallel cohort design, interventional research

condition: Hypertension

keyword: Hypertension, Blood Pressure

descriptionSummary:

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.

site:

Location ACCESS Martin T. Russo Family Health Center
Location Ashland Family Health Center

classifier: IPDSharing: Yes, IPDSharingDescription: Individual participant data will be shared through NHLBI BioLINCC., IPDSharingInfoType: Study Protocol, IPDSharingInfoType: Statistical Analysis Plan (SAP), IPDSharingInfoType: Informed Consent Form (ICF), IPDSharingInfoType: Clinical Study Report (CSR), IPDSharingInfoType: Analytic Code, IPDSharingTimeFrame: Data will be available within 1 year of study conclusion., IPDSharingAccessCriteria: Access to study data will be managed through NHLBI BioLINCC, Has Results: True, Oversight Classifier: oversightHasDmc True, Oversight Classifier: isFdaRegulatedDrug True, Oversight Classifier: isFdaRegulatedDevice False, AgreementPISponsorEmployee: False, AgreementRestrictiveAgreement: False

associatedParty
name: Washington University School of Medicine
role: Sponsor
classifier: OTHER

associatedParty
name: Mark Huffman
role: Principal investigator
party: PractitionerRole

associatedParty
name: Washington University School of Medicine
role: Lead sponsor
classifier: OTHER

associatedParty
name: ACCESS Community Health Network
role: Collaborator
classifier: OTHER

associatedParty
name: University of Sydney
role: Collaborator
classifier: OTHER

associatedParty
name: Mark D Huffman, PhD, MD
role: Principal investigator
party: Northwestern University Feinberg School of Medicine

associatedParty
name: Jody D Ciolino, PhD
role: Principal investigator
party: Overall Study Officials:

progressStatus
state: Completed

progressStatus
state: Overall study
actual: true
period: 2019-08-30 --> 2024-07-31

Recruitments

ActualNumber

Eligibility

NCT03640312 Eligibility Criteria

comparisonGroup
eligibility: 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.

comparisonGroup
eligibility: Candesartan: Patients randomized to the comparison arm will take a once daily 8mg candesartan.

objective
type: Primary
OutcomeMeasures
- Name Type Description Endpoint
* Change in Mean Systolic Blood Pressure Primary
Mean change (from baseline) in automated office systolic blood pressure adjusted for baseline values.

EvidenceVariable Change in Mean Systolic Blood Pressure (NCT03640312)

objective
type: Secondary
outcomeMeasure
name: Mean Systolic Blood Pressure
type: Secondary
description:
Mean automated office systolic blood pressure adjusted for baseline values.

endpoint: EvidenceVariable Mean Systolic Blood Pressure (NCT03640312)
outcomeMeasure
name: Change in Mean Diastolic Blood Pressure
type: Secondary
description:
Mean change (from baseline) in automated office diastolic blood pressure adjusted for baseline values.

endpoint: EvidenceVariable Change in Mean Diastolic Blood Pressure (NCT03640312)
outcomeMeasure
name: Mean Diastolic Blood Pressure
type: Secondary
description:
Mean automated office diastolic blood pressure adjusted for baseline values.

endpoint: EvidenceVariable Mean Diastolic Blood Pressure (NCT03640312)
outcomeMeasure
name: Proportion of Patients With Hypertension Control
type: Secondary
description:
Proportion of patients with hypertension control (percent with SBP < 130 mmHg and DBP <80 mmHg).

endpoint: EvidenceVariable Proportion of Patients With Hypertension Control (NCT03640312)
outcomeMeasure
name: Number of Patients Requiring Step up Treatment
type: Secondary
description:
Number of patients requiring step-up treatment.

endpoint: EvidenceVariable Number of Patients Requiring Step up Treatment (NCT03640312)
outcomeMeasure
name: Proportion of Patients With Adverse Event Free Hypertension Control
type: Secondary
description:
Proportion of patients with adverse event free hypertension control (percent with SBP < 130 mmHg and DBP <80 mmHg).

endpoint: EvidenceVariable Proportion of Patients With Adverse Event Free Hypertension Control (NCT03640312)
outcomeMeasure
name: Medication Adherence
type: Secondary
description:
Medication adherence defined by objective pill counts

endpoint: EvidenceVariable Medication Adherence (NCT03640312)
outcomeMeasure
name: Health-related Quality of Life
type: Secondary
description:
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.

endpoint: EvidenceVariable Health-related Quality of Life (NCT03640312)
outcomeMeasure
name: Change in Mean Systolic Blood Pressure
type: Secondary
description:
Mean change (from baseline) in automated office systolic blood pressure adjusted for baseline values.

endpoint: EvidenceVariable Change in Mean Systolic Blood Pressure (NCT03640312)

objective
type: Exploratory
outcomeMeasure
name: Percentage of Participants With Serious Adverse Events (SAEs)
type: Exploratory
description:
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.

endpoint: EvidenceVariable Percentage of Participants With Serious Adverse Events (SAEs) (NCT03640312)
outcomeMeasure
name: Percentage of Participants With Potentially Related Adverse Events
type: Exploratory
description:
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.

endpoint: EvidenceVariable Percentage of Participants With Potentially Related Adverse Events (NCT03640312)
outcomeMeasure
name: Rate of Adverse Events of Special Interest
type: Exploratory
description:
Rate of pre-specified adverse events that are known side effects of active ingredients at the participant level.

endpoint: EvidenceVariable Rate of Adverse Events of Special Interest (NCT03640312)
outcomeMeasure
name: Mean Change in Serum Potassium
type: Exploratory
description:
Mean change (from baseline) in continuous serum potassium.

endpoint: EvidenceVariable Mean Change in Serum Potassium (NCT03640312)
outcomeMeasure
name: Mean Change in Serum Sodium
type: Exploratory
description:
Mean change (from baseline) in continuous serum sodium.

endpoint: EvidenceVariable Mean Change in Serum Sodium (NCT03640312)
outcomeMeasure
name: Mean Change in Blood Urea Nitrogen
type: Exploratory
description:
Mean change (from baseline) in continuous blood urea nitrogen.

endpoint: EvidenceVariable Mean Change in Blood Urea Nitrogen (NCT03640312)
outcomeMeasure
name: Mean Change in Serum Creatinine
type: Exploratory
description:
Mean change in continuous serum creatinine.

endpoint: EvidenceVariable Mean Change in Serum Creatinine (NCT03640312)

result: Results Section for NCT03640312

Generated Narrative: EvidenceVariable #NCT03640312-drug------quartet-ldqt

Profile: VariableDefinition
name: NCT03640312_drug______quartet_ldqt
title: QUARTET LDQT
status: Active
description:
Ultra-low-dose combination therapy comprising four different blood pressure lowering drugs at 1/4 dosages. Taken once daily for 12 weeks.

handling: boolean variable
classifier: Intervention Type: DRUG

Generated Narrative: EvidenceVariable #NCT03640312-drug------candesartan

Profile: VariableDefinition
name: NCT03640312_drug______candesartan
title: Candesartan
status: Active
description:
Standard monotherapy of 8mg candesartan. Taken once daily for 12 weeks.

handling: boolean variable
classifier: Intervention Type: DRUG

Generated Narrative: Group #NCT03640312-comparison-group-0

Artifact Author: Computable Publishing®: [System]-to-FEvIR Converter:
identifier: FEvIR Linking Identifier/NCT03640312-comparison-group-0
title: NCT03640312 Comparison Group: QUARTET LDQT
status: Active
description:
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.

membership: Conceptual
code: Experimental
Characteristics
- Code Value[x] Exclude
* Exposed to Drug: QUARTET LDQT false

Generated Narrative: Group #NCT03640312-comparison-group-1

Artifact Author: Computable Publishing®: [System]-to-FEvIR Converter:
identifier: FEvIR Linking Identifier/NCT03640312-comparison-group-1
title: NCT03640312 Comparison Group: Candesartan
status: Active
description:
Patients randomized to the comparison arm will take a once daily 8mg candesartan.

membership: Conceptual
code: Active Comparator
Characteristics
- Code Value[x] Exclude
* Exposed to Drug: Candesartan false

Generated Narrative: PractitionerRole #NCT03640312-ResponsibleParty-0

practitioner: Mark Huffman
organization: Washington University School of Medicine
code: Professor of Medicine and Global Health Center Co-Director

Generated Narrative: Location #NCT03640312-Location-0

name: ACCESS Martin T. Russo Family Health Center
address: Bloomingdale Illinois 60108 United States
Positions
- Longitude Latitude
* -88.0809 41.95753

Generated Narrative: Location #NCT03640312-Location-1

name: Ashland Family Health Center
address: Chicago Illinois 60609 United States
Positions
- Longitude Latitude
* -87.65005 41.85003