Title: Does Levodopa (3,4-dihydroxy-L-phenylalanine) drug treatment in combination with routine NHS occupational and physi
Funder: Medical Research Council

Abstract: Scientific Abstract Design: A multicentre prospective randomised double blinded placebo controlled trial. 572 people with new stroke admitted to acute stroke services will be recruited. Setting: At least 8 UK stroke services within Stroke Local Research Networks(LRN) that have an acute inpatient rehabilitation facility and a service that allows rehabilitation treatments to be continued within the home setting. Target population: People with new stroke aged >=18 years, Rivermead Mobility Index(RMI) score <7 at time of recruitment(7-14 days post stroke). Exclusion criteria: Unlikely to survive more than 1 month, those requiring palliative care as advised by treating physician; Parkinsons disease; contraindications to L-dopa; unable to walk prior to stroke due to pre-existing co-morbidities(e.g. osteoarthritis). LRN staff will identify participants and consent. Intervention: L-dopa 100mg + carbidopa 25mg(as co-careldopa) will be given to patients as a single oral tablet 45-60 minutes before physical therapy or occupational therapy sessions (section 7.3) focused on motor skills(e.g. walking, dressing). Participants will be randomised equally between study drug and placebo within 7-14 days after stroke(stratification see section 5.1). Individual participant randomisation will be undertaken by the CTRU. The placebo will be given as an oral tablet 45-60 minutes before rehabilitation treatment. Production of trial medication blister packs will be formulated so placebo has the same appearance and packaging as active drug (Bilcare Ltd). Routine physical and occupational therapy will be administered to all patients in both groups. Treatments recorded using a standardized recording sheet. Phamacoadherence issues, see section 7. Outcomes: Primary outcome: The proportion of participants walking as defined by a score of 7 or above on the Rivermead Mobility Index, in the L-dopa and control intervention groups. This is a robust unambiguous clinical cut off indicator of L-dopa effect as it defines clearly the proportion of those walking at least 10 metres without assistance from another person, in the active and control groups at the primary end point (8 weeks) and the secondary end points (6,12 months). The RMI has been validated and extensively used in clinical studies. Secondary outcomes: (a) Barthel Index, self care dependency in stroke; (b)Motor Activity Log-28(AOU), functional upper limb activities; (c) Northwick Park Nursing Dependency measure, physical dependency from which care costs can be estimated; (d) Nottingham Extended Activities of Daily Living Scale, measures activities such as outdoor mobility and household tasks; (e) General Health Questionnaire 28, measures depression; (f) Caregiver Burden Index, measures carer strain; (g) EQ-5D, measure of health status for economic evaluation; (h) a proforma will be developed to record study drug adherence as part of rehabilitation treatment, type of rehabilitation treatment given, (i) Modified Rankin Scale to relate this study data to other clinical trials (see National Stroke Trials database), (j) RMI change score to capture changes in posture and movement, (k) Baseline routinely collected clinical data will be used to allow Edinburgh case mix adjuster to be completed and ensure that the the baseline clinical characteristics are comparable across the active and control groups. Data on concomitant medication will be recorded. We will also collect data on lesion location identified from routinely undertaken Brain CT scans at time of admission to stroke unit. We anticipate that this data would be available for the majority of patients recruited to the study. We will trial the use of a standardized proforma to collect the data on lesion location as part of the baseline assessment using the method described by Barber et al 2000. Follow up: Baseline assessments (prior to randomisation), 8 weeks (primary) after randomisation; 6 and 12 months after randomisation. 8 weeks was chosen as the


Research activity codes: 6.1 PHARMACEUTICALS
Health categories: STROKE