Clinical trial NCT04347330: Cardiovascular Risk Reduction in Atrial Fibrillation Trial
Official title: Cardiovascular Risk Reduction in Atrial Fibrillation Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Atrial Fibrillation
Hypertension
Keywords: Intensive blood pressure control
Cardiovascular events
Lead sponsor: Beijing Anzhen Hospital
Sponsor class: OTHER
Collaborators: name: Heart Health Research Center
name: The George Institute for Global Health, China
name: The George Institute for Global Health, Australia
name: Fukuoka University
First posted: 2020-04-15
Enrollment: 1675
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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 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.

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

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

Primary outcomes:
measure: Hierarchical composite cardiovascular outcomes
timeFrame: 5 years
Secondary outcomes:
measure: All-cause mortality
timeFrame: 5 years
measure: Main secondary cardiovascular outcomes
timeFrame: 5 years
measure: Main secondary renal outcomes
timeFrame: 5 years
measure: Change of the health state utility
timeFrame: 5 years
measure: Change of the self-report depression
timeFrame: 5 years
measure: Change of the self-report anxiety
timeFrame: 5 years
measure: Change of the concern of falling
timeFrame: 5 years
measure: Change of the frailty
timeFrame: 5 years
Other outcomes:
measure: Major bleeding
timeFrame: 5 years
measure: Peripheral arterial disease
timeFrame: 5 years
measure: Coronary revascularization
timeFrame: 5 years
Locations:
city: Beijing
country: China
facility: Beijing Anzhen Hospital
Study officials:
affiliation: Beijing Anzhen Hospital
name: Changsheng Ma, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: The George Institute for Global Health, China; Heart Health Research Centre
name: Craig S Anderson, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: Beijing Anzhen Hospital; The First Affiliated Hospital of Zhengzhou University
name: Jianzeng Dong, Doctor
role: PRINCIPAL_INVESTIGATOR
References: