Enhancement of Stroke Rehabilitation With Levodopa

NCT ID: NCT03735901

Last Updated: 2024-10-15

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 610 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-06-14
• Study Completion Date: 2029-06-30

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.

Conditions

Acute Stroke; Stroke Rehabilitation

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Experimental Intervention

White Investigational Medicinal Product (IMP)- capsules of a combination of IMP Levodopa 100mg/Carbidopa 25mg.

Group Type: ACTIVE_COMPARATOR

IMP Levodopa 100mg/Carbidopa 25mg

Intervention Type: DRUG

Study treatment will comprise 3 phases:

1. Dose escalation phase: On day 1-3, patients will receive IMP solely in the morning; on day 4-6 in the morning and at lunch time;

2. full study treatment phase: from day 7 to day 34, 3 times per day (tid).

3. Treatment will stop with a tapering phase: On day 35-37, patients will receive IMP in the morning and at lunch time; on day 38 and 39 solely in the morning.

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.

Group Type: PLACEBO_COMPARATOR

Matching placebo

Intervention Type: DRUG

Study treatment will comprise 3 phases:

1. Dose escalation phase: On day 1-3, patients will receive Placebo solely in the morning; on day 4-6 in the morning and at lunch time;

2. full study treatment phase: from day 7 to day 34, Placebo capsules 3 times per day (tid).

3. Treatment will stop with a tapering phase: On day 35-37, patients will receive Placebo in the morning and at lunch time; on day 38 and 39 solely in the morning.

Interventions

IMP Levodopa 100mg/Carbidopa 25mg

Study treatment will comprise 3 phases:

1. Dose escalation phase: On day 1-3, patients will receive IMP solely in the morning; on day 4-6 in the morning and at lunch time;

2. full study treatment phase: from day 7 to day 34, 3 times per day (tid).

3. Treatment will stop with a tapering phase: On day 35-37, patients will receive IMP in the morning and at lunch time; on day 38 and 39 solely in the morning.

Intervention Type: DRUG

Matching placebo

Study treatment will comprise 3 phases:

1. Dose escalation phase: On day 1-3, patients will receive Placebo solely in the morning; on day 4-6 in the morning and at lunch time;

2. full study treatment phase: from day 7 to day 34, Placebo capsules 3 times per day (tid).

3. Treatment will stop with a tapering phase: On day 35-37, patients will receive Placebo in the morning and at lunch time; on day 38 and 39 solely in the morning.

Intervention Type: DRUG

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Swiss National Science Foundation

OTHER

Sponsor Role: collaborator

University Hospital, Basel, Switzerland

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Stefan Engelter, Prof. MD

Role: PRINCIPAL_INVESTIGATOR

Felix-Platter Spital Basel

Locations

Kantonsspital Aarau, Neurozentrum

Aarau, , Switzerland

RehaClinic AG

Bad Zurzach, , Switzerland

Kantonsspital Baden

Baden, , Switzerland

Felix Platter Spital

Basel, , Switzerland

Stroke-Center Universitätsspital Basel

Basel, , Switzerland

Inselspital, Universitätsklinik für Neurologie

Bern, , Switzerland

Kantonsspital Graubünden, Departement Innere Medizin / Neurologie

Chur, , Switzerland

HFR Fribourg Hopital Cantonal, U. de Neurologie

Fribourg, , Switzerland

Centre hospitalier universitaire vaudois, Service de Neurologie

Lausanne, , Switzerland

HFR Meyriez-Murten, Clinique de Réhabilitation

Meyriez, , Switzerland

Kantonsspital Münsterlingen

Münsterlingen, , Switzerland

Reha Rheinfelden

Rheinfelden, , Switzerland

Kantonsspital St.Gallen, Klinik für Neurologie

Sankt Gallen, , Switzerland

Hôpital du Valais - Sion, Service de neurologie

Sion, , Switzerland

Hôpital du Valais - Sion

Sion, , Switzerland

Rehazentrum Valens, Klinik für Neurologie und Neurorehabilitation

Valens, , Switzerland

Cereneo Schweiz AG

Vitznau, , Switzerland

Zürcher RehaZentrum Wald

Wald, , Switzerland

Rheinburg Klinik AG

Walzenhausen, , Switzerland

Kantonsspital Winterthur

Winterthur, , Switzerland

Rehaklinik Zihlschlacht

Zihlschlacht, , Switzerland

Klinik Lengg AG

Zurich, , Switzerland

Head Stroke Center Klinik Hirslanden

Zurich, , Switzerland

Universitätsspital Zürich, Klinik für Neurologie

Zurich, , Switzerland

Countries

Switzerland

References

Engelter ST, Kaufmann JE, Zietz A, Luft AR, Polymeris A, Altersberger VL, Wiesner K, Wiegert M, Held JPO, Rottenberger Y, Schwarz A, Medlin F, Accolla EA, Foucras S, Kagi G, De Marchis GM, Politz S, Greulich M, Tarnutzer AA, Sturzenegger R, Katan M, Fischer U, Nedeltchev K, Schar J, Van Den Keybus Deglon K, Rapin PA, Salerno A, Seiffge DJ, Auer E, Lippert J, Bonati LH, Schuster-Amft C, Gaumann S, Chabwine JN, Humm A, Moller JC, Schweinfurther R, Bujan B, Jedrysiak P, Sandor PS, Gonzenbach R, Mylius V, Lutz D, Lienert C, Peters N, Michel P, Muri RM, Schadelin S, Hemkens LG, Ford GA, Lyrer PA, Gensicke H, Traenka C; ESTREL Investigators. Levodopa Added to Stroke Rehabilitation: The ESTREL Randomized Clinical Trial. JAMA. 2025 Sep 22:e2515185. doi: 10.1001/jama.2025.15185. Online ahead of print.

Reference Type: DERIVED

PMID: 40982270 (View on PubMed)

Other Identifiers

2018-02021; me16Engelter

Identifier Type: -

Identifier Source: org_study_id