Enhancement of Stroke Rehabilitation With Levodopa (ESTREL): a Randomized Placebo-controlled Trial
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 610
- 试验地点
- 24
- 主要终点
- Fugl-Meyer-Motor Assessment Score (FMMA)
研究概览
简要总结
Trial investigates the benefits and harms of Levodopa /Carbidopa 100/25mg compared to placebo (given in addition to standardized rehabilitation based on the principles of motor learning) and whether there is an association with a patient-relevant enhancement of functional recovery in acute stroke patients. Study participants will be randomized 1:1.
详细描述
Trial investigates whether Levodopa/Carbidopa compared to placebo given in addition to standardized rehabilitative therapy in patients with acute stroke is associated with
a) patient relevant improvements of physical function b) improvement in patient-self assessed general health aspects, pain, mood, anxiety, fatigue and social participation c) long-term sustainability of a patient-relevant improvement of motor function d) improvement of selective hand and wrist movement e) a higher rate of patients walking independently of the help of another person.
f) less severe impairment g) a higher level of activity of daily living h) improvements of quality of life (i) better cognitive performance (j) no signals of harms (i.e. indications for increased all-cause mortality, recurrent stroke, serious adverse events, and non-serious, pre-specified adverse events possibly related to the IMP)
Estrel-Longterm: optional prolongation of the observational study phase. To investigate the long-term outcomes of our study population the investigator aim to offer an optional prolongation of the observational phase to the participants through regular structured (once yearly) telephone visits.
The telephone visits will be carried out annually for the following 4 years.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
double-blind
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Acute ischemic or hemorrhagic (i.e. intracerebral hemorrhage excluding subarachnoid hemorrhage and cerebral venous sinus thrombosis) stroke ≤ 7 days prior to randomization
- •Clinically meaningful hemiparesis (i.e. scoring a total of ≥ 3 points on the following NIH stroke scale score items (i) motor arm, (ii) motor leg, (iii) limb ataxia; a distal arm paresis is equivalent to one of the aforementioned (i-iii))
- •Time of randomization ≥24-hours since thrombolysis or thrombectomy
- •In-hospital rehabilitation required
- •Capable to participate in standardized rehabilitation therapy
- •Informed consent of patient or next of kin
排除标准
- •Diagnosis of Parkinson's Disease
- •Use of Levodopa mandatory according to judgement of treating physician
- •Inability or unwillingness to comply with study procedures including adherence to study drug intake (orally, or via nasogastric tube or percutaneous endoscopic gastrostomy tube)
- •Severe aphasia (i.e. unable to follow two-stage-commands)
- •Previously dependent in the basal activities of daily living (defined as modified Ranking Scale prior to stroke > 3)
- •Pre-existing hemiparesis
- •Known hypersensitivity to Levodopa/Carbidopa and other contraindications for Levodopa/Carbidopa as outlined in the summary of product characteristics
- •Women who are pregnant or breast feeding, or who intend to become pregnant during the course of the study. Women of childbearing age must take a pregnancy test to be eligible for the study.
- •Lack of safe contraception, defined as: Female Participants of childbearing potential, not using and not willing to continue using a medically reliable method of contraception for the entire study duration, such as oral, injectable, or implantable contraceptives, or intrauterine contraceptive devices, or who are not using any other method considered sufficiently reliable by the Investigator in individual cases. Female Participants who are surgically sterilized / hysterectomized or post- menopausal for longer than 2 years are not considered as being of child- bearing potential.
研究组 & 干预措施
Experimental Intervention
White Investigational Medicinal Product (IMP)- capsules of a combination of IMP Levodopa 100mg/Carbidopa 25mg.
干预措施: IMP Levodopa 100mg/Carbidopa 25mg (Drug)
Control Intervention
Matching placebo, identical in aspect, texture, and taste when compared to the IMP. Procedures regarding route of administration, study treatment duration and treatment phases will be identical in the IMP- and the placebo-group.
干预措施: Matching placebo (Drug)
结局指标
主要结局
Fugl-Meyer-Motor Assessment Score (FMMA)
时间窗: Assessed 3 months +/- 14 days after randomization
FMMA is a stroke-specific impairment index designed to assess motor recovery. Scale items are scored on the basis of ability to complete the item using a 3-point ordinal scale (0=cannot perform; 1=performs partially and 2= performs fully). FMMA total scores range from 0 (no movements) to 100 (normal movements) with 66 points for movements of the upper limbs (FMMA-UE) and 34 for those of the lower limbs (FMMA-LE). A difference of 5.25 points for the upper extremity and 6 points for the lower extremity part of the score are described as minimal clinically important difference. For this study, based on these data, 6 points difference are considered a patient-relevant difference between both treatment groups for the primary endpoint.
次要结局
- NIH-Stroke Scale Score (NIHSS)(Assessed at Day 0 (Randomization), 5 weeks after randomization, 3 months +/- 14 days after randomization, 6 months +/- 20 days after randomization and 12 months +/- 30 days after randomization)
- Modified Rankin Scale Score (mRS)(Assessed at Day 0 (Randomization), 5 weeks after randomization, 3 months +/- 14 days after randomization, 6 months +/- 20 days after randomization and 12/24/36/48/60 months +/- 30 days after randomization)
- Stroke rehabilitation outcomes for disease specific morbidity and quality of life - PROMIS 29(Assessed 5 weeks after randomization, 3 months +/- 14 days after randomization, 6 months +/- 20 days after randomization and 12 months +/- 30 days after randomization)
- Stroke rehabilitation outcomes for disease specific morbidity and quality of life - PROMIS 10(Assessed 5 weeks after randomization, 3 months +/- 14 days after randomization, 6 months +/- 20 days after randomization and 12/24/36/48/60 months +/- 30 days after randomization)
- Patient-reported assessment of relevance of motor improvement(Assessed 5 weeks after randomization, 3 months +/- 14 days after randomization, 6 months +/- 20 days after randomization and 12/24/36/48/60 months +/- 30 days after randomization)
- Rivermead Mobility Index (RMI)(Assessed at Day 0 (Randomization), 5 weeks after randomization, 3 months +/- 14 days after randomization, 6 months +/- 20 days after randomization and 12/24/36/48/60 months +/- 30 days after randomization)
- Mortality (of any cause)(Throughout the whole study period from Day 1 to Visit 12/24/36/48/60 months +/- 30 days after randomization)
- Recurrent stroke (any type)(Throughout the whole study period from Day 1 to Visit 12/24/36/48/60 months +/- 30 days after randomization)
- Pre- specified Adverse Events of Interest(Throughout the study period from Day 1 to Visit 3 ( 3 months +/- 14 days after randomization))
- Motricity Index (MI)(Assessed at Day 0 (Randomization), 5 weeks after randomization, 3 months +/- 14 days after randomization, 6 months +/- 20 days after randomization and 12 months +/- 30 days after randomization)
- Trunk Control Test (TCT)(Assessed at Day 0 (Randomization), 5 weeks after randomization, 3 months +/- 14 days after randomization, 6 months +/- 20 days after randomization and 12 months +/- 30 days after randomization)
- Action Research Arm Test (ARAT)(Assessed at Day 0 (Randomization), 5 weeks after randomization, 3 months +/- 14 days after randomization, 6 months +/- 20 days after randomization and 12 months +/- 30 days after randomization)
- Box- and Block Test (BBT)(Assessed at Day 0 (Randomization), 5 weeks after randomization, 3 months +/- 14 days after randomization, 6 months +/- 20 days after randomization and 12 months +/- 30 days after randomization)
- Functional Ambulation Categories (FAC)(Assessed at Day 0 (Randomization), 5 weeks after randomization, 3 months +/- 14 days after randomization, 6 months +/- 20 days after randomization and 12/24/36/48/60 months +/- 30 days after randomization)
- Ten-Meter Walk Test (10MWT)(Assessed at Day 0 (Randomization), 5 weeks after randomization, 3 months +/- 14 days after randomization, 6 months +/- 20 days after randomization and 12 months +/- 30 days after randomization)
- Jamar dynamometer testing (JDT)(Assessed at Day 0 (Randomization), 5 weeks after randomization, 3 months +/- 14 days after randomization, 6 months +/- 20 days after randomization and 12 months +/- 30 days after randomization)
- Montreal Cognitive Assessment (MoCA)(Assessed at Day 0 (Randomization), 5 weeks after randomization, 3 months +/- 14 days after randomization, 6 months +/- 20 days after randomization and 12 months +/- 30 days after randomization)
- Fugl-Meyer-Motor Assessment Score (FMMA)(Assessed at Day 0 (Randomization), 5 weeks after randomization, 6 months +/- 20 days after randomization and 12 months +/- 30 days after randomization)
- Daily activity measurement with movement sensor(Assessed at Day 0 (Randomization), 5 weeks after randomization, 3 months +/- 14 days after randomization, 6 months +/- 20 days after randomization and 12 months +/- 30 days after randomization)
- Serious Adverse Event (SAE)(Throughout the study period from Day 1 to Visit 3 ( 3 months +/- 14 days after randomization))