Generated Narrative: ResearchStudy 367879 version: 32; Last updated: 2025-09-13 13:13:52+0000; Language: en Profile: StudyRegistryRecord Artifact Author: Computable Publishing®: ClinicalTrials.gov-to-FEvIR Converter: 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 2025-09-13. 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. PMID: 36116516; PMCID: PMC10236716. 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 * 62 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
Ultra-low-dose combination therapy comprising four different blood pressure lowering drugs at 1/4 dosages. Taken once daily for 12 weeks.
Standard monotherapy of 8mg candesartan. Taken once daily for 12 weeks.
Computable Publishing®: [System]-to-FEvIR Converter
NCT03640312 Comparison Group: 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.
NCT03640312 Comparison Group: Candesartan
Patients randomized to the comparison arm will take a once daily 8mg candesartan.
Washington University School of Medicine
Professor of Medicine and Global Health Center Co-Director
ACCESS Martin T. Russo Family Health Center
Computable Publishing®: ClinicalTrials.gov-to-FEvIR Converter
Efficacy and Safety of a Quadruple Ultra-low-dose Treatment for Hypertension
A Double Blind Randomized Controlled Trial to Assess the Efficacy and Safety of a Quadruple Ultra-low-dose Treatment for Hypertension (QUARTET USA)
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 2025-09-13. Available at: https://fevir.net/resources/ResearchStudy/367879. Computable resource at: https://fevir.net/resources/ResearchStudy/367879#json.
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; PMCID: PMC10236716.
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.
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.
IPDSharingDescription: Individual participant data will be shared through NHLBI BioLINCC.
IPDSharingInfoType: Statistical Analysis Plan (SAP)
IPDSharingInfoType: Informed Consent Form (ICF)
IPDSharingInfoType: Clinical Study Report (CSR)
IPDSharingTimeFrame: Data will be available within 1 year of study conclusion.
IPDSharingAccessCriteria: Access to study data will be managed through NHLBI BioLINCC
Oversight Classifier: oversightHasDmc True
Oversight Classifier: isFdaRegulatedDrug True
Oversight Classifier: isFdaRegulatedDevice False
Northwestern University Feinberg School of Medicine
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.
Candesartan: Patients randomized to the comparison arm will take a once daily 8mg candesartan.
Mean change (from baseline) in automated office systolic blood pressure adjusted for baseline values.
Mean automated office systolic blood pressure adjusted for baseline values.
Mean change (from baseline) in automated office diastolic blood pressure adjusted for baseline values.
Mean automated office diastolic blood pressure adjusted for baseline values.
Proportion of Patients With Hypertension Control
Proportion of patients with hypertension control (percent with SBP \< 130 mmHg and DBP \<80 mmHg).
Number of Patients Requiring Step up Treatment
Number of patients requiring step-up treatment.
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).
Medication adherence defined by objective pill counts
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.
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.
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.
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.
Mean change (from baseline) in continuous serum potassium.
Mean change (from baseline) in continuous serum sodium.
Mean change (from baseline) in continuous blood urea nitrogen.
Mean change in continuous serum creatinine.