Indian Trial of Tranexamic Acid in Spontaneous Intracerebral Haemorrhage
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 发起方
- 入组人数
- 3,400
- 试验地点
- 93
- 主要终点
- Death
研究概览
简要总结
This multicenter, pragmatic randomized, open-label clinical trial aims to assess whether Tranexamic Acid improves outcomes in adult patients with spontaneous intracerebral haemorrhage.
The participants presenting within 4.5 hours of the onset of symptoms of stroke with intracerebral haemorrhage confirmed on Computed Tomography (CT Scan) will be randomized into two groups in a 1:1 ratio using a central online randomization. The treatment arm will consist of giving intravenously 2 grams of Tranexamic Acid in 100 ml 0.9% sodium chloride administered over 45 minutes. Control arm patients will receive standard of care treatment as per the institutional protocol. In both arms, intensive systolic blood pressure reduction to less than 140 mmHg will be done using antihypertensive medications, which has to be achieved within one hour and will be maintained over next seven days. The choice of antihypertensive drug will depend on the clinician's preference.
Both groups will have a repeat CT scan after 24 hours to check for any increase in the haematoma volume. Any deterioration in the neurological status will warrant urgent brain imaging. On day 7, the patient will be assessed for their NIHSS score and mRS score. On day 90, quality of life and the functional outcome will be assessed.
详细描述
Global Burden of Disease, Injury and Risk factors for hemorrhagic stroke 2010 estimated the burden of spontaneous intracranial haemorrhage (sICH) in India is profound (32 -49%) and it is associated with high mortality (up to 63 %) due to haematoma expansion which occurs in 38% of ICH within first few hours of presentation. Early administration of haemostatic drugs has been used in patients with trauma and was associated with improved outcomes. Similarly, if haemostatic drugs are administered early, which can be a simple and cost-effective intervention, may improve the functional outcomes in patients with sICH. Recently, the Tranexamic acid for hyperacute primary IntraCerebral Haemorrhage (TICH 2 trial), which was done to see the effectiveness of the administration of tranexamic acid on hematoma expansion and functional outcomes at three months in patients who presented with sICH within 8 hours of presentation of symptoms onset, showed a decrease in haematoma expansion but no improvement in functional outcome at 90 days. Further larger randomized control trials are required to ascertain the effect of early administration of Tranexamic acid (TXA) in sICH. In India patients present to hospitals in the early stages that have developed symptoms after sICH and we propose to study the effect of intravenous Tranexamic Acid for hyperacute primary intracerebral haemorrhage within 4.5 hours of sICH.
Trial Population:
This multi-centric study will be conducted at 50 stroke centres in India associated with the INSTRuCT Network. All patients presenting with symptoms of stroke to the hospital and admitted to the stroke units will be screened for eligibility and if met, will be included in the study. The INTRINSIC trial intends to recruit 3400 patients.
Trial Design:
INTRINSIC Trial will be a multicenter, randomized, open-label, clinical trial. The participants will be randomized into two groups in a 1:1 ratio using a central database of INSTRuCT central online randomization. The baseline characteristics will be adjusted to stroke severity using the NIHSS score and the volume of haematoma. The treatment arm will consist of giving intravenously 2 grams of Tranexamic Acid in 100 ml sodium chloride 0.9 % administered over 45 minutes. Control arm patients will receive standard of care management as per the institutional protocol. Both groups will have a repeat CT scan after 24 hours to check for any increase in the haematoma volume. Any deterioration in the Glasgow Coma Scale (GCS) will warrant urgent brain CT scans. Antihypertensive drugs used and their doses to control BP will be recorded for up to 7 days. On day 7, the patient will be assessed for their NIHSS score and mRS score. On day 90, quality of life and the functional outcome will be assessed.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Participant)
盲法说明
Open-label
入排标准
- 年龄范围
- 18 Years 至 99 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adult patients aged more than 18 years, presenting with non- traumatic intracerebral haemorrhage within 4.5 hours of onset of stroke symptoms
排除标准
- •Patients with ICH secondary to anticoagulation, thrombolysis, or known underlying structural abnormality such as arteriovenous malformation, aneurysm, tumor, venous thrombosis or due to known hereditary coagulation disorders.
- •Contraindication to TXA.
- •Concurrent participation in another trial.
- •Pre-stroke life expectancy <3 months (e.g. advanced metastatic cancer).
- •Glasgow coma scale (GCS) ⩽
- •ICH secondary to trauma.
- •Women of childbearing potential, pregnant, or breastfeeding at randomization.
- •Geographical or other factors that prohibit follow-upto 90 days.
- •Concurrent or planned treatment with any other hemostatic agents.
- •ICH volume >60 mL as measured by ABC/2 method.
研究组 & 干预措施
Intervention Arm
The treatment arm will consist of giving intravenously 2 grams of Tranexamic Acid in 100 ml sodium chloride 0.9 % administered over 45 minutes. Intensive systolic blood pressure reduction to less than 140 mmHg will be done using antihypertensive agents (intravenous and/or oral) which is to be achieved within one hour and has to be maintained over seven days. BP monitoring is done every 15 minutes in the first hour and thereafter every hour for the next six hours after the initiation of intensive BP control. The choice of antihypertensive will depend on the clinician's preference.
干预措施: Tranexamic acid injection (Drug)
Control Arm
The control arm will receive a standard of care management as per the institutional practice. Intensive systolic blood pressure reduction to less than 140 mmHg will be done using antihypertensive (intravenous and/or oral) which is to be achieved within one hour and has to be maintained over seven days. BP monitoring is done for every 15 minutes in the first hour and thereafter every hour for the next six hours after the initiation of intensive BP control. The choice of antihypertensive will depend on the clinician's preference.
结局指标
主要结局
Death
时间窗: 30 days
Death at day 30. Absolute difference of 3% between intervention and control arm for the number of participants that expired at day 30
次要结局
- Neurological impairment(7 days)
- Quality of life EQ-5D(90 days)
- modified Rankin Scale (mRS)(90 days)
- Change in hematoma volume(24 hours)
研究者
Jeyaraj D Pandian
Principal and Professor, Department of Neurology
Christian Medical College and Hospital, Ludhiana, India