Trials under the INSTRuCT Network
To begin with the INSTRuCT network will focus on stroke clinical trials a minimum of 4-5 in the area of acute stroke, secondary prevention and rehabilitation. INSTRUcT will collaborate with professional, industry, academic and funding bodies (within and outside the country) to enhance and increase Indian stroke clinical trials.
ENCHANTED
Enhanced Control of Hypertension and Thrombolysis Stroke study (ENCHANTED) Funded by NHRMC, Australia. ENCHANTED was an independent, investigator initiated, international collaborative, quasi-factorial randomised controlled trial involving a package of 2 linked comparative treatment arms, which aimed to address 4 key questions in patients eligible for thrombolysis in the hyperacute phase of ischaemic stroke. Worldwide, 2227 patients were recruited between March 2017 and April 2018. Of these 35 were contributed from India from 15 centres of the INSTRuCT Network.
Results: The BP intensive lowering arm ( < 140 mm Hg) was not shown to be superior to guideline recommended BP lowering (< 180 mm Hg) for primary disability outcome. The results have been published in the Lancet.
Read the full publication here.
SPRINT India
The Secondary Prevention By Structured Semi-Interactive Stroke Prevention Package in INDIA (SPRINT INDIA) Trial will be carried out to assess the role of a structured semi-interactive stroke prevention package to reduce the risk of recurrent strokes, myocardial infarction and death in patients with sub-acute stroke after one month.
Read the full publications here:
RESTORE
AyuRvedic TrEatment in the Rehabilitation of IschemicSTrOke Patients in India: A Randomized controllEd trial (RESTORE) for a) finding out the safety and efficacy of Ayurvedic treatment in the rehabilitation of stroke patients b) comparing the efficacy of Ayurvedic treatment over conventional physiotherapy in the rehabilitation of stroke patients.
Trials under Phase-II of the INSTRuCT Network
INTRINSIC
In the INTRINSIC Trial, we seek to investigate the effectiveness of intravenous TXA for hyperacute primary ICH within 4.5 hrs by reducing death at 7 days. INTRINSIC Trial will be a randomised controlled trial at INSTRuCT Centres in India which will recruit 3,600 participants aged ≥ 18 years with primary ICH presenting within 4.5 hrs of symptoms onset and Glasgow Come Scale >7. Patients with traumatic haemorrhage, subarachnoid haemorrhage, ICH due to bleeding disorders and patients who will be surgically managed will be excluded. Computerized randomization (1:1) using a central database of INSTRuCT will be done. After 24hrs all patients will undergo a repeat CT scan of the brain to assess the hematoma expansion. The primary outcome will be mortality at 7 days and the secondary outcome will be assessed by mRS (modified Rankin Scale) at 3 months.
STENOSIS
Longterm Single versus Dual Antiplatelet Therapy In Patients With Intracranial Atherosclerotic Disease: A Randomized Trial. (STENOSIS)
The exact duration of dual antiplatelet therapy is uncertain among patients with ischemic stroke due to symptomatic intracranial stenosis due to intracranial atherosclerotic disease (ICAD). Current recommendations, based on the SAMPRISS trial suggest that three months of dual antiplatelet therapy (DAPT) using aspirin and clopidogrel with optimisation of risk factor control seems the correct approach. The current trial aims to study whether a total of 12 months of DAPT with aspirin and clopidogrel is superior to three months of DAPT among patients with a recent ischemic stroke due to symptomatic and significant intracranial atherosclerotic disease (>or=50% stenosis). All patients with a recent ischemic stroke due to ICAD and started on DAPT within 15 days of their stroke onset will be randomised after 3 months of receiving DAPT in a 1:1 fashion with either continuation of DAPT or aspirin and placebo for an extended period of 9 months. The primary efficacy outcome includes recurrence of ischemic stroke at 12 months and primary safety outcome any minor or major bleeding. The secondary outcome includes a composite of any myocardial infarction or death due to any vascular cause. A sample size of 2200 patients is planned for the study.
REOPEN
Randomised Trial of Biosimilar TNK Versus tPA during Endovascular Therapy (EVT) For Acute Ischemic Stroke Due To Large Vessel Occlusions (REOPEN)
Acute ischemic stroke (AIS) due to large vessel occlusions (LVO) is a serious and potentially disabling situation. Bridging therapy with intravenous (IV) thrombolysis and endovascular treatment (EVT) is the current standard of care in LVO’s. However, an incompletely answered question is whether one the thrombolytic agent is better over another during the bridging therapy. This is an open-label, superiority driven, randomised controlled trial with blinded outcome analysis (PROBE design). All eligible patients (as per inclusion and exclusion criteria) and presenting within 4.5 hours of AIS due to proximal large vessel occlusion will be randomised in a 1:1 fashion to either biosimilar TNK (0.25mg/kg, max 20 mg) or TPA (0.9mg/kg, max 90mg) prior to the treatment with EVT. Patients will be assessed for outcomes at 3 months using mRS score and recanalization at first of angiography and at the end of the procedure using TICI (thrombolysis in cerebral ischemia) score. Safety outcomes will be assessed for any major or minor intracranial or systemic bleeding. A sample size of 372 patients is planned for the study
MOBILITY
Mobile Medical Application based Post Stroke care Strategy ( MOBILITY ) for survivors and their caregivers: A Randomized Controlled Trial Informal caregivers of stroke patients who are usually family members have little or no skills to care the stroke patients at home. It has been well reported that the quality of life of stroke survivors is adversely affected due to dependency on untrained caregivers and morbidity. An initial pilot study using Medical Application based Post Stroke care Strategy (MAPSS) shows a signal of efficacy in reducing post stroke complications which is now being tested in a large clinical trial.
Aim and Objectives: To train the caregivers of stroke patients using a mobile application which has elaborative post stroke care strategies which would help them in caring the patients at home so that bedridden stroke survivors would face a substantially lesser post stroke morbidity and mortality.
Methods: A multicentric randomized (PROBE design) study. The bedridden stroke patients and their primary caregivers will be recruited after screening for inclusion and exclusion criteria following an informed written consent. Major Inclusions: Recent (< 3 month) acute ischemic \ haemorrhagic \ undifferentiated stroke, Stroke survivors with significant residual disability (requiring help from another person for everyday activities) \ bedridden patients (mRS>3), caregivers willing and able to provide care to the patients after discharge and caregivers \ patients must have a smartphone \ tablet with internet facility and should be competent as well as willing to use an app as a health care tool. After baseline assessment of patients and their primary caregivers using screening tool, participants will be randomized into 2 study groups i.e. control group (the patients of this group will be provided booklet on stroke information and link of care videos to their smartphone) and intervention group (the patients of this group will be provided booklet on stroke information along with the smartphone app). Participating centers will be provided with the mobile application link and app will be available in multiple languages. The recruitment of patients will be carried out for a period of around 24 months and follow up at 3 months and 6 months after recruitment in the study. Expected Outcomes: Development of bed-sore, aspiration pneumonia, catheter associated urinary tract infection (CAUTI), shoulder pain (>=5 score on Numerical rating scale (NRS>=5)), deep vein thrombosis (DVT) within first 3 months after recruitment in the study will be assessed.
Primary Outcome: Incidence of bed-sore reduction will be taken as primary outcome. Caregiver stress index (CSI) score will be assessed by using modified caregiver strain index (MCSI), Health related Quality of life of patients (score) will be assessed by using VAS of EQ-5D scale, Functional status \ disability level of the patients will be assessed by using modified Rankin Scale (mRS), Stroke severity level will be assessed by using National institute of health and stroke scale (NIHSS), Number of hospital visits and hospitalization will be assessed by using validated semi structured interview schedule, Cost effectiveness will be assessed by validated tools.