Rationale and design of "Can Very Low Dose Rivaroxaban (VLDR) in addition to dual antiplatelet therapy improve thrombotic status in acute coronary syndrome (VaLiDate-R)" study : A randomised trial modulating endogenous fibrinolysis in patients with acute coronary syndrome.

Impaired endogenous fibrinolysis is novel biomarker that can identify patients with ACS at increased cardiovascular risk. The addition of Very Low Dose Rivaroxaban (VLDR) to dual antiplatelet therapy has been shown to reduce cardiovascular events but at a cost of increased bleeding and is therefore not suitable for all-comers. Targeted additional pharmacotherapy with VLDR to improve endogenous fibrinolysis may improve outcomes in high-risk patients, whilst avoiding unnecessary bleeding in low-risk individuals. The VaLiDate-R study (ClinicalTrials.gov Identifier: NCT03775746, EudraCT: 2018-003299-11) is an investigator-initiated, randomised, open-label, single centre trial comparing the effect of 3 antithrombotic regimens on endogenous fibrinolysis in 150 patients with ACS. Subjects whose screening blood test shows impaired fibrinolytic status (lysis time > 2000s), will be randomised to one of 3 treatment arms in a 1:1:1 ratio: clopidogrel 75 mg daily (Group 1); clopidogrel 75 mg daily plus rivaroxaban 2.5 mg twice daily (Group 2); ticagrelor 90 mg twice daily (Group 3), in addition to aspirin 75 mg daily. Rivaroxaban will be given for 30 days. Fibrinolytic status will be assessed during admission and at 2, 4 and 8 weeks. The primary outcome measure is the change in fibrinolysis time from admission to 4 weeks follow-up, using the Global Thrombosis Test. If VLDR can improve endogenous fibrinolysis in ACS, future large-scale studies would be required to assess whether targeted use of VLDR in patients with ACS and impaired fibrinolysis can translate into improved clinical outcomes, with reduction in major adverse cardiovascular events in this high-risk cohort.

The Herts and Minds study: feasibility of a randomised controlled trial of Mentalization-Based Treatment versus usual care to support the wellbeing of children in foster care.

BACKGROUND: There is a lack of well-designed randomized controlled trials (RCTs) to investigate the efficacy of psychological therapies for children in foster care with emotional and behavioural difficulties. Mentalization-based therapy (MBT) focuses on supporting the carer-child relationship by promoting reflective capacity. This study examined the feasibility and acceptability of an RCT of MBT, delivered in a family-format, for children who are in foster care in the UK. METHOD: Herts and Minds was a phase II, blinded feasibility RCT with follow-up of at 12 and 24 weeks post-randomisation. Participants were children (age 5-16) in foster care referred to a targeted mental health service, who had some level of difficulty as identified by the Strengths and Difficulties Questionnaire (SDQ). Aims were to assess: the feasibility of recruitment processes and study uptake; capacity to train mental health practitioners to deliver MBT to an acceptable level of treatment integrity; establish acceptability and credibility of MBT as an intervention for children in foster care; establish feasibility and acceptability to participants of conducting an RCT; and estimate the likely treatment efficacy effect size. Participants were randomly allocated to either MBT (n = 15) or Usual Clinical Care (UCC) (n = 21) individually or in sibling groups. A range of qualitative and quantitative data was gathered to assess feasibility. RESULTS: Feasibility was established with regard to: capacity to recruit participants to a study; capacity to train mental health practitioners to deliver MBT to an acceptable level of treatment integrity; acceptability and credibility of MBT; and feasibility and acceptability to participants of conducting an RCT. A number of issues made it difficult to estimate a likely treatment efficacy effect size. CONCLUSION: With modifications, it is feasible to run an RCT of MBT for children in foster care. Both the therapy and research design were acceptable to participants, but modifications may be needed regarding both the timing of assessments and the identification of appropriate primary outcome measures. Given the lack of evidenced based therapies for this population, such a trial would be a significant contribution to the field. Findings may be useful for other groups planning clinical trials of psychological therapies for children in foster care. TRIAL REGISTRATION: ISRCTN 90349442 . The trial was retrospectively registered on 6 May 2016.

The Herts and minds study: evaluating the effectiveness of mentalization-based treatment (MBT) as an intervention for children in foster care with emotional and/or behavioural problems: a phase II, feasibility, randomised controlled trial.

BACKGROUND: A significant proportion of children in the social care system in England present with mental health problems, with the majority experiencing some form of emotional and behavioural difficulties. The most effective treatments for these children are currently unknown, partly due to a lack of robust, controlled studies. Researchers have identified a number of obstacles to conducting well-designed research with this population, making the need to test the feasibility of a randomised controlled trial especially important. METHODS/DESIGN: This protocol outlines a two-arm, randomised control feasibility trial to explore the acceptability and credibility of mentalization-based treatment (MBT) as a treatment for reducing emotional and behavioural difficulties in looked after children and to test the possibility of addressing a number of methodological challenges to conducting high-quality research with this population. MBT is a relatively new intervention which, in the adaptation of the model tested here, includes many of the features of therapy identified in NICE guidelines as necessary to support children in care. The two arms are MBT and usual clinical care (UCC). The study will take place in Hertfordshire Partnership University NHS Foundation Trust with follow-up at 12 and 24 weeks. DISCUSSION: This study will aim to ascertain whether it is worthwhile and feasible to progress to testing the intervention in a full-scale definitive randomised controlled trial (RCT). This study therefore has the potential to improve our understanding of the obstacles to conducting high-quality research with this very vulnerable population, and in the medium term, could help to improve the stability of foster placements and the emotional well-being of children in care. TRIAL REGISTRATION: ISRCTN90349442.