Clinical trial NCT03735901: Enhancement of Stroke Rehabilitation With Levodopa
Official title: Enhancement of Stroke Rehabilitation With Levodopa (ESTREL): a Randomized Placebo-controlled Trial
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Acute Stroke
Stroke Rehabilitation
Keywords: Levodopa / Carbidopa
Fugl-Meyer-Motor-Assessment (FMMA)
Acute ischemic stroke
Acute hemorrhagic stroke
Rehabilitation
Recovery
Randomized controlled trial
Lead sponsor: University Hospital, Basel, Switzerland
Sponsor class: OTHER
Collaborators: name: Swiss National Science Foundation
First posted: 2018-11-08
Enrollment: 610
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Study participants will be randomized 1:1
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Fugl-Meyer-Motor Assessment Score (FMMA)
timeFrame: Assessed 3 months +/- 14 days after randomization
Secondary outcomes:
measure: NIH-Stroke Scale Score (NIHSS)
timeFrame: 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
measure: Modified Rankin Scale Score (mRS)
timeFrame: 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
measure: Stroke rehabilitation outcomes for disease specific morbidity and quality of life - PROMIS 29
timeFrame: Assessed 5 weeks after randomization, 3 months +/- 14 days after randomization, 6 months +/- 20 days after randomization and 12 months +/- 30 days after randomization
measure: Stroke rehabilitation outcomes for disease specific morbidity and quality of life - PROMIS 10
timeFrame: 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
measure: Patient-reported assessment of relevance of motor improvement
timeFrame: 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
measure: Rivermead Mobility Index (RMI)
timeFrame: 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
measure: Mortality (of any cause)
timeFrame: Throughout the whole study period from Day 1 to Visit 12/24/36/48/60 months +/- 30 days after randomization
measure: Recurrent stroke (any type)
timeFrame: Throughout the whole study period from Day 1 to Visit 12/24/36/48/60 months +/- 30 days after randomization
measure: Pre- specified Adverse Events of Interest
timeFrame: Throughout the study period from Day 1 to Visit 3 ( 3 months +/- 14 days after randomization)
measure: Motricity Index (MI)
timeFrame: 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
measure: Trunk Control Test (TCT)
timeFrame: 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
measure: Action Research Arm Test (ARAT)
timeFrame: 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
measure: Box- and Block Test (BBT)
timeFrame: 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
measure: Functional Ambulation Categories (FAC)
timeFrame: 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
measure: Ten-Meter Walk Test (10MWT)
timeFrame: 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
measure: Jamar dynamometer testing (JDT)
timeFrame: 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
measure: Montreal Cognitive Assessment (MoCA)
timeFrame: 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
measure: Daily activity measurement with movement sensor
timeFrame: 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
measure: Serious Adverse Event (SAE)
timeFrame: Throughout the study period from Day 1 to Visit 3 ( 3 months +/- 14 days after randomization)
measure: Fugl-Meyer-Motor Assessment Score (FMMA)
timeFrame: Assessed at Day 0 (Randomization), 5 weeks after randomization, 6 months +/- 20 days after randomization and 12 months +/- 30 days after randomization
Other outcomes:
Locations:
city: Aarau
country: Switzerland
facility: Kantonsspital Aarau, Neurozentrum
city: Bad Zurzach
country: Switzerland
facility: RehaClinic AG
city: Baden
country: Switzerland
facility: Kantonsspital Baden
city: Basel
country: Switzerland
facility: Felix Platter Spital
city: Basel
country: Switzerland
facility: Stroke-Center Universitätsspital Basel
city: Bern
country: Switzerland
facility: Inselspital, Universitätsklinik für Neurologie
city: Chur
country: Switzerland
facility: Kantonsspital Graubünden, Departement Innere Medizin / Neurologie
city: Fribourg
country: Switzerland
facility: HFR Fribourg Hopital Cantonal, U. de Neurologie
city: Lausanne
country: Switzerland
facility: Centre hospitalier universitaire vaudois, Service de Neurologie
city: Meyriez
country: Switzerland
facility: HFR Meyriez-Murten, Clinique de Réhabilitation
city: Münsterlingen
country: Switzerland
facility: Kantonsspital Münsterlingen
city: Rheinfelden
country: Switzerland
facility: Reha Rheinfelden
city: Sion
country: Switzerland
facility: Hôpital du Valais - Sion, Service de neurologie
city: Sion
country: Switzerland
facility: Hôpital du Valais - Sion
city: St.Gallen
country: Switzerland
facility: Kantonsspital St.Gallen, Klinik für Neurologie
city: Valens
country: Switzerland
facility: Rehazentrum Valens, Klinik für Neurologie und Neurorehabilitation
city: Vitznau
country: Switzerland
facility: Cereneo Schweiz AG
city: Wald
country: Switzerland
facility: Zürcher RehaZentrum Wald
city: Walzenhausen
country: Switzerland
facility: Rheinburg Klinik AG
city: Winterthur
country: Switzerland
facility: Kantonsspital Winterthur
city: Zihlschlacht
country: Switzerland
facility: Rehaklinik Zihlschlacht
city: Zürich
country: Switzerland
facility: Klinik Lengg AG
city: Zürich
country: Switzerland
facility: Head Stroke Center Klinik Hirslanden
city: Zürich
country: Switzerland
facility: Universitätsspital Zürich, Klinik für Neurologie
Study officials:
affiliation: Felix-Platter Spital Basel
name: Stefan Engelter, Prof. MD
role: PRINCIPAL_INVESTIGATOR
References: