Cardiovascular Risk Reduction in Atrial Fibrillation Trial (CRAFT)

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.

Study Overview

• Status: Recruiting
• Conditions: Hypertension; Atrial Fibrillation
• Intervention / Treatment: Drug: Intensive BP Control; Drug: Standard BP Control

Detailed Description

The CRAFT trial will include approximately 1675 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 4-year period at approximately 100 to 150 clinical centres and the first patient will be followed for up to 5 years.

• Study Type: Interventional
• Enrollment (Estimated): 1675
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Xin Du, Doctor; Phone Number: 86-10-64420102; Email: duxinheart@sina.com
• Study Contact Backup: Name: Chao Jiang, Doctor; Phone Number: 86-10-84005361; Email: superj@zju.edu.cn

Study Locations

• China
  • Beijing, China
    • Recruiting
    • Beijing Anzhen Hospital
    • Contact: Xin Du, MD, PhD
    • Contact: Chao Jiang, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intensive BP Control; 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.	Drug: Intensive BP Control; 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.; Other Names: Control of home SBP to a target of 120mmHg
Active Comparator: Standard BP Control; 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.	Drug: Standard BP Control; 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.; Other Names: Control of home SBP to a target of 135mmHg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hierarchical composite cardiovascular outcomes	a hierarchical composite of cardiovascular death, number of strokes, time to first stroke, number of MI, time to first MI, number of HF, and time to first HF	5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
All-cause mortality	Time to all deaths.	5 years
Main secondary renal outcomes	Time to the first occurrence of chronic kidney disease progression or incident albuminuria.	5 years
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.	5 years
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.	5 years
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.	5 years
Change of the frailty	Change of the frailty (measured by the 5-item FRAIL scale) from baseline to the end of the study.	5 years
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.	5 years
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.	5 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Major bleeding	Time to the first major bleeding (ISTH definition).	5 years
Peripheral arterial disease	Time to the first peripheral arterial disease, including systemic embolism, carotid and peripheral revascularization, abdominal aortic aneurysm repair, and other objectively defined PAD events.	5 years
Coronary revascularization	Time to the first occurrence of percutaneous coronary intervention or coronary artery bypass grafting	5 years

Collaborators and Investigators

• Sponsor: Beijing Anzhen Hospital
• Collaborators: The George Institute for Global Health, Australia; The George Institute for Global Health, China; Fukuoka University; Heart Health Research Center
• Investigators: Principal Investigator: Craig S Anderson, Doctor, The George Institute for Global Health, China; Heart Health Research Centre; Principal Investigator: Jianzeng Dong, Doctor, Beijing Anzhen Hospital; The First Affiliated Hospital of Zhengzhou University; Principal Investigator: Changsheng Ma, Doctor, Beijing Anzhen Hospital

Study record dates

Study Major Dates

• Study Start (Actual): August 31, 2020
• Primary Completion (Estimated): June 1, 2024
• Study Completion (Estimated): December 1, 2025

Study Registration Dates

• First Submitted: March 29, 2020
• First Submitted That Met QC Criteria: April 12, 2020
• First Posted (Actual): April 15, 2020

Study Record Updates

• Last Update Posted (Estimated): December 11, 2023
• Last Update Submitted That Met QC Criteria: December 4, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: Cardiovascular events; Intensive blood pressure control
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Arrhythmias, Cardiac; Atrial Fibrillation
• Other Study ID Numbers: 2020-005

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No