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Cardiovascular Risk Reduction in Atrial Fibrillation Trial (CRAFT)

Primary Purpose

Atrial Fibrillation, Hypertension

Status
Recruiting
Phase
Not Applicable
Locations
China
Study Type
Interventional
Intervention
Intensive BP Control
Standard BP Control
Sponsored by
Beijing Anzhen Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Atrial Fibrillation focused on measuring Intensive blood pressure control, Cardiovascular events

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Screening and Run-in Assessment

All patients with documented AF (paroxysmal, persistent) and standard office SBP 140-179 mmHg if not on BP-lowering drugs or 125-164 mmHg with BP-lowering drugs, will be screened for inclusion into the run-in assessment phase.

The run-in assessment is for 2 weeks. In the run-in phase, patients should be treated according to guideline recommendation, with combined antihypertension agents. Patients should also be guided to measure and upload HBPM measurements correctly. BP measurements (3 readings in the morning and 3 readings in the evening) are required to be uploaded every day for a week before the end of run-in assessment. Patients with average home SBP 125-154 mmHg during the run-in assessment are considered eligible for study inclusion. If home SBP ≥155 mmHg or <125 mmHg at the time of run-in assessment, another 2 weeks run-in phase can be extended, during which time antihypertensive drugs can be titrated according to the BP lowering algorithm used in this study.

Inclusion Criteria

  1. Adults, ≥18 years old
  2. Documented AF: persistent atrial fibrillation or at least two episodes of intermittent atrial fibrillation in the previous 6 months.
  3. Home SBP 125-154 mmHg, defined as average of all SBP readings (at least 3 readings 1 min apart in the morning before taking antihypertensive drugs and evening before going to sleep) during the run-in assessment.
  4. One or more cardiovascular risk factors: (1) Prior history of thromboembolism: defined as any of the following criteria: a) ischemic stroke; b) transient ischemic attack (TIA); c) systemic embolism (SE); (2) Diabetes mellitus (DM): defined as any of the following criteria: a) use of oral hypoglycemic drugs or insulin; b) random blood glucose values ≥11.1 mmol/L in the presence of classic symptoms of hyperglycemia; c) fasting plasma glucose values ≥7.0 mmol/L; d) two-hour plasma glucose values ≥11.1 mmol/L during an oral glucose tolerance test; e) HbA1C values ≥6.5%; (3) Coronary artery disease or Peripheral artery disease: defined as any of the following criteria: a) Previous myocardial infarction (MI), percutaneous coronary intervention (PCI), coronary artery bypass grafting (CABG), carotid endarterectomy (CE), carotid stenting; b) Peripheral artery disease (PAD) with revascularization; c) Acute coronary syndrome with or without resting ECG change, ECG changes on a graded exercise test, or positive cardiac imaging study; d) At least a 50% diameter stenosis of a coronary, carotid, or lower extremity artery; e) Abdominal aortic aneurysm ≥5 cm with or without repair; (4) Chronic kidney disease (CKD): defined as estimated glomerular filtration rate (eGFR) 30-59ml/min/1.73m2 based on the latest lab value within the past 6 months; (5) Age ≥65 years old

Exclusion Criteria

  1. Successful AF ablation (no documented recurrence of AF, atrial flutter, or atrial tachycardia lasting >30s)
  2. Moderate-to-severe mitral stenosis, or mechanical heart valve replacement
  3. Home SBP ≥145 mmHg while already taking ≥4 full dose BP lowering agents, indicating resistant hypertension or poor adherence.
  4. Unable to upload home BP readings for at least 5 days during the run-in assessment.
  5. An indication for a specific BP lowering medication (e.g., beta-blocker following acute myocardial infarction) that the person is not taking, without evidence of intolerance. The screenee should be on the appropriate dose of such medication before assessing whether he/she meets the CRAFT inclusion criteria.
  6. Known secondary cause of hypertension that causes concern regarding safety of the protocol.
  7. One minute standing SBP < 110 mm Hg. Not applicable if unable to stand due to wheelchair use.
  8. Diagnosis of polycystic kidney disease
  9. Glomerulonephritis treated with or likely to be treated with immunosuppressive therapy
  10. eGFR <30 mL/min/1.73m2 or end-stage renal disease (ESRD)
  11. Cardiovascular event or procedure (as defined above as Coronary artery disease or Peripheral artery disease for study entry) or hospitalization for unstable angina within last 3 months
  12. Heart failure with reduced left ventricular ejection fraction (< 40%), or New York Heart Association Class III-IV
  13. Individuals who have been previously diagnosed with dementia by their physicians
  14. A medical condition likely to limit survival to less than 3 years, or a cancer diagnosed and treated within the past two years that, in the judgment of clinical study staff, would compromise a participant's ability to comply with the protocol and complete the trial.
  15. Any factors judged by the investigator to be likely to limit adherence to interventions. For example, active alcohol or substance abuse, significant memory or behavioural disorder.
  16. Currently participating in another clinical trial (intervention study). Note: Patient must wait until the completion of his/her activities or the completion of the other trial before being screened for CRAFT.
  17. Living in the same household as an already randomized CRAFT participant
  18. Any organ transplant
  19. Unintentional weight loss > 10% in last 6 months
  20. Pregnancy, currently trying to become pregnant, or of child-bearing potential and not using birth control

Sites / Locations

  • Beijing Anzhen HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Intensive BP Control

Standard BP Control

Arm Description

Participants randomized into the Intensive BP Control arm will have a goal of home SBP <120mmHg. For most participants in the Intensive Group, a two- or three-drug regimen should be initiated at randomization. Following the randomization visit, addition of another drug or medication dose titration is indicated if home SBP is ≥120 mmHg. Monthly visits will continue in the Intensive Group until home SBP <120 mmHg or no more titration planned. If the home SBP is not <120 mmHg at the every 6-month visit, then an antihypertensive drug from a class different from what is being taken should be added, rather than up-titration the dosage of previous drugs, unless there are compelling reasons against this practice.

Participants randomized into the Standard BP Control arm will have a goal of home SBP <135mmHg. The Standard BP protocol is designed to achieve a home SBP of 130-134 mmHg in as many participants as possible. Following the randomization visit, medication dose titration or addition of another drug is indicated if home SBP ≥135 mmHg. Monthly visits will continue in the Standard Group when home SBP ≥155 mmHg. Down titration (a reduction of the dose or number of antihypertensive drugs) should be carried out if the home SBP is <125 mmHg.

Outcomes

Primary Outcome Measures

Composite cardiovascular outcomes
Time to the first occurrence of a cardiovascular death, non-fatal stroke (ischemic or hemorrhagic), non-fatal myocardial infarction, or hospitalization for heart failure. All cardiovascular endpoint definitions are modifications based on 2017 SCTI definitions.

Secondary Outcome Measures

All-cause mortality
Time to all deaths.
Main secondary cardiovascular outcomes
Time to the first occurrence of the components of the primary outcome: cardiovascular death, stroke, myocardial infarction, hospitalization for heart failure.
Main secondary renal outcomes
Time to the first occurrence of chronic kidney disease progression or incident albuminuria.
Main secondary cognitive outcomes (CRAFT-Cog sub-study)
Decline in global cognitive function evaluated by the integrated and standardized z score of 5 cognitive domains. (Episodic memory, Processing speed, Working memory, Verbal ability, and Visual-spatial ability, measured by Basic Cognitive Ability Tests, a computerized cognitive testing system)
Change of the health state utility
Change of the health state utility (measured by the EuroQoL Group 5-Dimension Self-Report Questionnaire) from baseline to the end of the study.
Change of the self-report depression
Change of the depression (measured by the Patient Health Questionnaire-9) from baseline to the end of the study.
Change of the self-report anxiety
Change of the anxiety (measured by the Zung Self-rating Anxiety Scale) from baseline to the end of the study.
Change of the concern of falling
Change of the concern of falling (measured by the Short Fall Self-Efficacy Scale International) from baseline to the end of the study.
Change of the frailty
Change of the frailty (measured by the 5-item FRAIL scale) from baseline to the end of the study.

Full Information

First Posted
March 29, 2020
Last Updated
July 31, 2023
Sponsor
Beijing Anzhen Hospital
Collaborators
Heart Health Research Center, The George Institute for Global Health, China, The George Institute for Global Health, Australia, Fukuoka University
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1. Study Identification

Unique Protocol Identification Number
NCT04347330
Brief Title
Cardiovascular Risk Reduction in Atrial Fibrillation Trial
Acronym
CRAFT
Official Title
Cardiovascular Risk Reduction in Atrial Fibrillation Trial
Study Type
Interventional

2. Study Status

Record Verification Date
July 2023
Overall Recruitment Status
Recruiting
Study Start Date
August 31, 2020 (Actual)
Primary Completion Date
August 2025 (Anticipated)
Study Completion Date
August 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Beijing Anzhen Hospital
Collaborators
Heart Health Research Center, The George Institute for Global Health, China, The George Institute for Global Health, Australia, Fukuoka University

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Atrial fibrillation (AF) is a serious public health problem because of its increasing incidence and prevalence in the aging population. AF is associated with elevated risks of death, stroke, coronary event, heart failure, cognitive decline, and chronic kidney disease. To identify preventive interventions for major cardiovascular events beyond effective anticoagulation should be a major priority in the treatment of AF patients. The CRAFT study is a 2-arm, multicenter, randomized clinical trial designed to test whether intensive blood pressure control will reduce the risk of major cardiovascular events in AF patients.
Detailed Description
The CRAFT trial will include approximately 6000 AF patients with home SBP 125-154 mmHg and at least another cardiovascular risk factor. The trial aims to compare the effects of randomization to a treatment program of an intensive SBP goal (target home SBP <120mmHg) with randomization to a treatment program of a standard goal (target home SBP <135mmHg). The primary hypothesis is that cardiovascular event rates will be lower in the intensive arm. Participants will be recruited over a 3-year period at approximately 100 to 150 clinical centres and the first patient will be followed for up to 5 years.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Atrial Fibrillation, Hypertension
Keywords
Intensive blood pressure control, Cardiovascular events

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
Outcomes Assessor
Allocation
Randomized
Enrollment
6000 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Intensive BP Control
Arm Type
Experimental
Arm Description
Participants randomized into the Intensive BP Control arm will have a goal of home SBP <120mmHg. For most participants in the Intensive Group, a two- or three-drug regimen should be initiated at randomization. Following the randomization visit, addition of another drug or medication dose titration is indicated if home SBP is ≥120 mmHg. Monthly visits will continue in the Intensive Group until home SBP <120 mmHg or no more titration planned. If the home SBP is not <120 mmHg at the every 6-month visit, then an antihypertensive drug from a class different from what is being taken should be added, rather than up-titration the dosage of previous drugs, unless there are compelling reasons against this practice.
Arm Title
Standard BP Control
Arm Type
Active Comparator
Arm Description
Participants randomized into the Standard BP Control arm will have a goal of home SBP <135mmHg. The Standard BP protocol is designed to achieve a home SBP of 130-134 mmHg in as many participants as possible. Following the randomization visit, medication dose titration or addition of another drug is indicated if home SBP ≥135 mmHg. Monthly visits will continue in the Standard Group when home SBP ≥155 mmHg. Down titration (a reduction of the dose or number of antihypertensive drugs) should be carried out if the home SBP is <125 mmHg.
Intervention Type
Drug
Intervention Name(s)
Intensive BP Control
Other Intervention Name(s)
Control of home SBP to a target of 120mmHg
Intervention Description
Participants in the Intensive group have a goal of home SBP <120 mm Hg. The CRAFT BP treatment protocol is flexible in terms of the choice and doses of antihypertensive medications, but there should be preferences among the drug classes, based on CVD outcome trials results and current guidelines. Use of once-daily antihypertensive agents will be encouraged unless alternative frequency is indicated/necessary. Combination of different classes of agents are encouraged to achieve the home SBP goal. Medications will not be provided by the CRAFT study.
Intervention Type
Drug
Intervention Name(s)
Standard BP Control
Other Intervention Name(s)
Control of home SBP to a target of 135mmHg
Intervention Description
Participants in the Standard group has a goal of home SBP <135 mmHg. The same principle of BP treatment in the Intensive BP arm will be used for the Standard BP arm. Medications will not be provided by the CRAFT study.
Primary Outcome Measure Information:
Title
Composite cardiovascular outcomes
Description
Time to the first occurrence of a cardiovascular death, non-fatal stroke (ischemic or hemorrhagic), non-fatal myocardial infarction, or hospitalization for heart failure. All cardiovascular endpoint definitions are modifications based on 2017 SCTI definitions.
Time Frame
5 years
Secondary Outcome Measure Information:
Title
All-cause mortality
Description
Time to all deaths.
Time Frame
5 years
Title
Main secondary cardiovascular outcomes
Description
Time to the first occurrence of the components of the primary outcome: cardiovascular death, stroke, myocardial infarction, hospitalization for heart failure.
Time Frame
5 years
Title
Main secondary renal outcomes
Description
Time to the first occurrence of chronic kidney disease progression or incident albuminuria.
Time Frame
5 years
Title
Main secondary cognitive outcomes (CRAFT-Cog sub-study)
Description
Decline in global cognitive function evaluated by the integrated and standardized z score of 5 cognitive domains. (Episodic memory, Processing speed, Working memory, Verbal ability, and Visual-spatial ability, measured by Basic Cognitive Ability Tests, a computerized cognitive testing system)
Time Frame
2 years
Title
Change of the health state utility
Description
Change of the health state utility (measured by the EuroQoL Group 5-Dimension Self-Report Questionnaire) from baseline to the end of the study.
Time Frame
5 years
Title
Change of the self-report depression
Description
Change of the depression (measured by the Patient Health Questionnaire-9) from baseline to the end of the study.
Time Frame
5 years
Title
Change of the self-report anxiety
Description
Change of the anxiety (measured by the Zung Self-rating Anxiety Scale) from baseline to the end of the study.
Time Frame
5 years
Title
Change of the concern of falling
Description
Change of the concern of falling (measured by the Short Fall Self-Efficacy Scale International) from baseline to the end of the study.
Time Frame
5 years
Title
Change of the frailty
Description
Change of the frailty (measured by the 5-item FRAIL scale) from baseline to the end of the study.
Time Frame
5 years
Other Pre-specified Outcome Measures:
Title
Major bleeding
Description
Time to the first major bleeding (ISTH definition).
Time Frame
5 years
Title
Peripheral arterial disease
Description
Time to the first peripheral arterial disease, including systemic embolism, carotid and peripheral revascularization, abdominal aortic aneurysm repair, and other objectively defined PAD events.
Time Frame
5 years
Title
Coronary revascularization
Description
Time to the first occurrence of percutaneous coronary intervention or coronary artery bypass grafting
Time Frame
5 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Screening and Run-in Assessment All patients with documented AF (paroxysmal, persistent) and standard office SBP 140-179 mmHg if not on BP-lowering drugs or 125-164 mmHg with BP-lowering drugs, will be screened for inclusion into the run-in assessment phase. The run-in assessment is for 2 weeks. In the run-in phase, patients should be treated according to guideline recommendation, with combined antihypertension agents. Patients should also be guided to measure and upload HBPM measurements correctly. BP measurements (3 readings in the morning and 3 readings in the evening) are required to be uploaded every day for a week before the end of run-in assessment. Patients with average home SBP 125-154 mmHg during the run-in assessment are considered eligible for study inclusion. If home SBP ≥155 mmHg or <125 mmHg at the time of run-in assessment, another 2 weeks run-in phase can be extended, during which time antihypertensive drugs can be titrated according to the BP lowering algorithm used in this study. Inclusion Criteria Adults, ≥18 years old Documented AF: persistent atrial fibrillation or at least two episodes of intermittent atrial fibrillation in the previous 6 months. Home SBP 125-154 mmHg, defined as average of all SBP readings (at least 3 readings 1 min apart in the morning before taking antihypertensive drugs and evening before going to sleep) during the run-in assessment. One or more cardiovascular risk factors: (1) Prior history of thromboembolism: defined as any of the following criteria: a) ischemic stroke; b) transient ischemic attack (TIA); c) systemic embolism (SE); (2) Diabetes mellitus (DM): defined as any of the following criteria: a) use of oral hypoglycemic drugs or insulin; b) random blood glucose values ≥11.1 mmol/L in the presence of classic symptoms of hyperglycemia; c) fasting plasma glucose values ≥7.0 mmol/L; d) two-hour plasma glucose values ≥11.1 mmol/L during an oral glucose tolerance test; e) HbA1C values ≥6.5%; (3) Coronary artery disease or Peripheral artery disease: defined as any of the following criteria: a) Previous myocardial infarction (MI), percutaneous coronary intervention (PCI), coronary artery bypass grafting (CABG), carotid endarterectomy (CE), carotid stenting; b) Peripheral artery disease (PAD) with revascularization; c) Acute coronary syndrome with or without resting ECG change, ECG changes on a graded exercise test, or positive cardiac imaging study; d) At least a 50% diameter stenosis of a coronary, carotid, or lower extremity artery; e) Abdominal aortic aneurysm ≥5 cm with or without repair; (4) Chronic kidney disease (CKD): defined as estimated glomerular filtration rate (eGFR) 30-59ml/min/1.73m2 based on the latest lab value within the past 6 months; (5) Age ≥65 years old Exclusion Criteria Successful AF ablation (no documented recurrence of AF, atrial flutter, or atrial tachycardia lasting >30s) Moderate-to-severe mitral stenosis, or mechanical heart valve replacement Home SBP ≥145 mmHg while already taking ≥4 full dose BP lowering agents, indicating resistant hypertension or poor adherence. Unable to upload home BP readings for at least 5 days during the run-in assessment. An indication for a specific BP lowering medication (e.g., beta-blocker following acute myocardial infarction) that the person is not taking, without evidence of intolerance. The screenee should be on the appropriate dose of such medication before assessing whether he/she meets the CRAFT inclusion criteria. Known secondary cause of hypertension that causes concern regarding safety of the protocol. One minute standing SBP < 110 mm Hg. Not applicable if unable to stand due to wheelchair use. Diagnosis of polycystic kidney disease Glomerulonephritis treated with or likely to be treated with immunosuppressive therapy eGFR <30 mL/min/1.73m2 or end-stage renal disease (ESRD) Cardiovascular event or procedure (as defined above as Coronary artery disease or Peripheral artery disease for study entry) or hospitalization for unstable angina within last 3 months Heart failure with reduced left ventricular ejection fraction (< 40%), or New York Heart Association Class III-IV Individuals who have been previously diagnosed with dementia by their physicians A medical condition likely to limit survival to less than 3 years, or a cancer diagnosed and treated within the past two years that, in the judgment of clinical study staff, would compromise a participant's ability to comply with the protocol and complete the trial. Any factors judged by the investigator to be likely to limit adherence to interventions. For example, active alcohol or substance abuse, significant memory or behavioural disorder. Currently participating in another clinical trial (intervention study). Note: Patient must wait until the completion of his/her activities or the completion of the other trial before being screened for CRAFT. Living in the same household as an already randomized CRAFT participant Any organ transplant Unintentional weight loss > 10% in last 6 months Pregnancy, currently trying to become pregnant, or of child-bearing potential and not using birth control
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Xin Du, Doctor
Phone
86-10-64420102
Email
duxinheart@sina.com
First Name & Middle Initial & Last Name or Official Title & Degree
Chao Jiang, Doctor
Phone
86-10-84005361
Email
superj@zju.edu.cn
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Changsheng Ma, Doctor
Organizational Affiliation
Beijing Anzhen Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Craig S Anderson, Doctor
Organizational Affiliation
The George Institute for Global Health, China; Heart Health Research Centre
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Jianzeng Dong, Doctor
Organizational Affiliation
Beijing Anzhen Hospital; The First Affiliated Hospital of Zhengzhou University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Beijing Anzhen Hospital
City
Beijing
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Xin Du, MD, PhD
First Name & Middle Initial & Last Name & Degree
Chao Jiang, MD

12. IPD Sharing Statement

Plan to Share IPD
No

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Cardiovascular Risk Reduction in Atrial Fibrillation Trial

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