The DARS trial was a multicentre, prospective, randomised, double-blinded, placebo-controlled trial of NHS PT and OT treatment alone compared with NHS PT and OT treatment in addition to up to 6 weeks of co-careldopa treatment for patients admitted to acute stroke services after new or recurrent stroke.64Outcome measures were obtained at 8 weeks, 6 months and 12 months following
randomisation.
Changes to trial design
Recruitment into the trial was lower than anticipated. Screening logs were reviewed during the early stages of recruitment, and after approximately 11 months of recruitment the following relaxations were made to the eligibility criteria to increase the number of potential patients who could participate in the trial without compromising the scientific validity of the research: (1) inclusion of patients with new or recurrent stroke (previously new stroke only) and (2) extension of the recruitment window from 2 weeks to 42 days post stroke.
Trial timelines
The original project plan was to deliver the project in 45 months. However, the recruitment and
implementation of the project were more challenging than anticipated and the funder granted a 21-month funded extension. The main reasons for the extension are outlined below:
(a) The initial setup time was prolonged as a result of a worldwide lack of availability of the
investigational medicinal product (IMP) (Sinemet), which delayed drug procurement for the recruiting sites. Thus, trial setup increased from 9 months to 16 months because of a global shortage of the active drug.
(b) Challenges in identifying and recruiting suitable people with stroke led to much lower recruitment estimates per centre than those envisaged by the sites at trial setup. Thus, many more centres than planned were required in order to recruit 572 patients within a reasonable time frame.
(c) Implementation of the DARS trial was challenging for the following reasons– the need to deliver seamless trial intervention across acute and community NHS trusts, the need to administer medication with therapy sessions in both hospital and community settings, and service reconfiguration during the recruitment period.
The impact of these challenges was not fully realised at the outset of the trial. These issues led to a delay in the start of the site setup and poor recruitment rates for the first few months.
Participants
Patient recruitment
Patients admitted to participating NHS stroke services after experiencing a new or recurrent stroke were screened for trial entry from admission up to 42 days post stroke. It is possible that a patient’s condition could improve during the 42 days post stroke and the patient was reviewed during this period to reassess eligibility. Screening logs were maintained for all patients admitted to stroke services after a new or recurrent stroke.
Potential patients were identified by local Stroke Research Network (SRN) staff in liaison with ward nurses and therapists, and were provided with verbal information about the trial. Patients interested in receiving further information were provided with a detailed patient information booklet and a patient digital versatile disc (DVD) that provided an overview of the trial and a visual aid to increase understanding of the implications of participating in the trial. The principal investigator (PI) (or medically qualified member of the trial team) obtained written informed consent. When the patient was able to comprehend but unable to sign or date the consent form, provision was made for completion of the consent form by an independent person.
Carer recruitment
Carers of eligible and consenting patients were approached and consented at the time of patient enrolment to provide information relating to carer burden.
Eligibility
Inclusion criteria
l New or recurrent clinically diagnosed ischaemic or haemorrhagic (excluding subarachnoid haemorrhage) stroke within 5 to 42 days prior to randomisation.
l Could not independently walk (that is, without the use of physical assistance)≥ 10 metres indoors. l Achieved a score of< 7 points on the RMI, scored by a professional.
l Were expected to need rehabilitation treatment. l Were≥ 18 years of age.
l Were able to give informed consent.
l Were able to access continuity of rehabilitation treatment following discharge from hospital (i.e. continuity of rehabilitation available within 5 days following discharge).
l Were expected to be able to comply with the treatment schedule.
l Were expected to be in hospital for at least their first two doses of trial medication.
Coenrolment into another trial was permitted if it had been agreed with the chief investigator of the relevant studies and provided that it would not confound the results of the DARS trial nor overburden the patient, attribution of AEs was not compromised and there were no potential interactions.
Exclusion criteria
l Not expected to survive for 2 months following stroke.
l A diagnosis of Parkinson’s disease, severe medical or surgical illness, or severe psychosis. l Known hypersensitivity or contraindications to co-careldopa.
l Symptomatic orthostatic hypotension.
l Required physical assistance from at least one person to walk prior to stroke due to pre-existing comorbidities (e.g. heart failure or osteoarthritis).
l Pregnancy, lactation or, in the case of women of child-bearing potential, unwillingness to use medically approved contraception during treatment and for 1 month after treatment had finished.
l Participation in another interventional drug or treatment therapy trial.
l Inability to walk≥ 10 metres indoors prior to stroke [with a walking aid if necessary, but without physical assistance, which, in this context, means help from one or more person(s)].
Potential trials for coenrolment with the DARS trial were considered by the chief investigator and trial management team if (1) it was agreed with the chief investigator of the relevant studies, (2) it did not confound the results of the DARS trial, (3) it did not overburden the patient, (4) attribution of causality to AEs was not compromised and (5) there were no potential interactions of trial interventions.
Carer eligibility
A carer was defined as an individual identified by the patient as their main informal carer who provides the patient with practical support a minimum of once per week. Carers had to provide written informed consent to be eligible for participation. Presence of a carer was not a prerequisite for patient enrolment.