The Danish Non-vitamin K Antagonist Oral Anticoagulation Study. A Cluster Randomized Study Comparing Safety and Efficacy of Edoxaban, Apixaban, Rivaroxaban and Dabigatran for Oral Anticoagulation in Patients With Venous Thromboembolism.
试验速览
- 阶段
- 4 期
- 状态
- 进行中（未招募）
- 入组人数
- 5,000
- 试验地点
- 26
- 主要终点
- Primary efficacy outcome: a composite endpoint of new venous thromboembolism or all-cause death.
研究概览
简要总结
No randomized head-to-head comparison between the individual Non-vitamin K Antagonist Oral Anticoagulants (NOAC) exists. The DANNOAC-VTE study is a nationwide cluster randomized cross-over study comparing efficacy and safety of the four NOACs, edoxaban, apixaban, rivaroxaban and dabigatran for oral anticoagulation in venous thromboembolism across Danish hospitals.
详细描述
No randomized head-to-head comparison between the individual Non-vitamin K Antagonist Oral Anticoagulants (NOAC) exists, but such data are warranted to evaluate if the four NOACs are equal in treatment of venous thromboembolism (VTE) without an additional cost of increased bleeding risk. Furthermore, classic randomized trials are highly selective, as elderly and/or fragile patients and patients with comorbidity are underrepresented. Therefore, there is a need of randomized trials that include a broader population of patients.
The DANNOAC-VTE study is a nationwide cluster randomized cross-over study comparing efficacy and safety of the four NOACs, edoxaban, apixaban, rivaroxaban and dabigatran for oral anticoagulation in VTE across Danish hospitals. The aim of the present study is to: 1) examine if the four NOACs are equally effective in treatment of VTE without increasing the risk of major bleeding requiring hospitalization; 2) conduct a randomized study that includes elderly and fragile patients and patients with comorbidity that would otherwise not be included in a traditional randomized clinical trial.
For a variety of reasons, Danish hospitals and clinicians often prefer one particular NOAC. This can make work simpler for the busy clinician, although there may also be economic advantages on a local or a regional larger scale. For a period of two years, this study will replace this individually or hospital preferred selection with a random selection. The hospitals and clinics that participate in this study will be randomly selected to primarily use one specific NOAC for 6 months at a time during a total period of two years. This only applies to patients with VTE that are selected by the physician to be eligible for NOAC treatment. VTE refers to deep vein thrombosis and pulmonary embolism, or a combination of both.
Endpoints
- Primary efficacy outcome: a composite endpoint of new venous thromboembolism or all-cause death.
- Secondary efficacy outcomes: Individually components of the primary endpoints; new venous thromboembolism or all-cause death.
- Primary safety outcome: bleeding requiring hospitalization.
- Other effect measures:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
盲法说明
The Outcome Assessor will only have a code of each drug and a code for each cluster. Therefore he will not know what drug the clusters have been using. The randomization key will be safely stored at servers at "Statens Serums Institute" (An institute under the Danish Ministry of Health). After the primary and secondary outcome have been evaluated data will be unblinded.
入排标准
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •A diagnosis of VTE in outpatient clinic or as discharge diagnosis after hospitalization.
- •A claimed prescription of a NOAC from a Danish pharmacy within 14 days of discharge or outpatient clinic visit.
排除标准
- •A prescription of a NOAC within 90 days prior to hospitalization or outpatient clinic visit for VTE.
- •Patients with NOAC preference apart from preference consistent with current cluster randomized NOAC.
- •Other contraindications mentioned in the "Summary of Product Characteristics" for the respective NOAC.
研究组 & 干预措施
Dabigatran
After randomization, the cluster will use dabigatran to all their patients with venous thromboembolism when possible for six months. Hereafter the cluster will use the other three NOACs for six months one at the time.
干预措施: Dabigatran Etexilate Oral Capsule (Drug)
Dabigatran
After randomization, the cluster will use dabigatran to all their patients with venous thromboembolism when possible for six months. Hereafter the cluster will use the other three NOACs for six months one at the time.
干预措施: Rivaroxaban Oral Tablet (Drug)
Dabigatran
After randomization, the cluster will use dabigatran to all their patients with venous thromboembolism when possible for six months. Hereafter the cluster will use the other three NOACs for six months one at the time.
干预措施: Edoxaban Oral Tablet (Drug)
Dabigatran
After randomization, the cluster will use dabigatran to all their patients with venous thromboembolism when possible for six months. Hereafter the cluster will use the other three NOACs for six months one at the time.
干预措施: Apixaban Oral Tablet (Drug)
Rivaroxaban
After randomization, the cluster will use rivaroxaban to all their patients with venous thromboembolism when possible for six months. Hereafter the cluster will use the other three NOACs for six months one at the time.
干预措施: Dabigatran Etexilate Oral Capsule (Drug)
Rivaroxaban
After randomization, the cluster will use rivaroxaban to all their patients with venous thromboembolism when possible for six months. Hereafter the cluster will use the other three NOACs for six months one at the time.
干预措施: Rivaroxaban Oral Tablet (Drug)
Rivaroxaban
After randomization, the cluster will use rivaroxaban to all their patients with venous thromboembolism when possible for six months. Hereafter the cluster will use the other three NOACs for six months one at the time.
干预措施: Edoxaban Oral Tablet (Drug)
Rivaroxaban
After randomization, the cluster will use rivaroxaban to all their patients with venous thromboembolism when possible for six months. Hereafter the cluster will use the other three NOACs for six months one at the time.
干预措施: Apixaban Oral Tablet (Drug)
Edoxaban
After randomization, the cluster will use edoxaban to all their patients with venous thromboembolism when possible for six months. Hereafter the cluster will use the other three NOACs for six months one at the time.
干预措施: Dabigatran Etexilate Oral Capsule (Drug)
Edoxaban
After randomization, the cluster will use edoxaban to all their patients with venous thromboembolism when possible for six months. Hereafter the cluster will use the other three NOACs for six months one at the time.
干预措施: Rivaroxaban Oral Tablet (Drug)
Edoxaban
After randomization, the cluster will use edoxaban to all their patients with venous thromboembolism when possible for six months. Hereafter the cluster will use the other three NOACs for six months one at the time.
干预措施: Edoxaban Oral Tablet (Drug)
Edoxaban
After randomization, the cluster will use edoxaban to all their patients with venous thromboembolism when possible for six months. Hereafter the cluster will use the other three NOACs for six months one at the time.
干预措施: Apixaban Oral Tablet (Drug)
Apixaban
After randomization, the cluster will use apixaban to all their patients with venous thromboembolism when possible for six months. Hereafter the cluster will use the other three NOACs for six months one at the time.
干预措施: Dabigatran Etexilate Oral Capsule (Drug)
Apixaban
After randomization, the cluster will use apixaban to all their patients with venous thromboembolism when possible for six months. Hereafter the cluster will use the other three NOACs for six months one at the time.
干预措施: Rivaroxaban Oral Tablet (Drug)
Apixaban
After randomization, the cluster will use apixaban to all their patients with venous thromboembolism when possible for six months. Hereafter the cluster will use the other three NOACs for six months one at the time.
干预措施: Edoxaban Oral Tablet (Drug)
Apixaban
After randomization, the cluster will use apixaban to all their patients with venous thromboembolism when possible for six months. Hereafter the cluster will use the other three NOACs for six months one at the time.
干预措施: Apixaban Oral Tablet (Drug)
结局指标
主要结局
Primary efficacy outcome: a composite endpoint of new venous thromboembolism or all-cause death.
时间窗: 6 months.
First occurrence of new venous thromboembolism or all-cause death. Information of endpoints and comorbidity is obtained from the Danish National Patient Register based on ICD-10 diagnostic codes and information of vital status and date of death will be obtained from the Central Person Register. Information of prescribed drug will be obtained using information from the Danish Registry of Medicinal Product Statistics.
次要结局
- Secondary efficacy outcome: All-cause death.(6 months.)
- Primary safety outcome: bleeding requiring hospitalization.(6 months.)
- Secondary efficacy outcome: New venous thromboembolism.(6 months.)
研究者
Gunnar Gislason
MD,PhD
University Hospital, Gentofte, Copenhagen