Tranexamic acid for intracerebral haemorrhage within 2 hours of onset: protocol of a phase II randomised placebo-controlled double-blind multicentre trial

RationaleHaematoma growth is common early after intracerebral haemorrhage (ICH), and is a key determinant of outcome. Tranexamic acid, a widely available antifibrinolytic agent with an excellent safety profile, may reduce haematoma growth.Methods and designStopping intracerebral haemorrhage with tranexamic acid for hyperacute onset presentation including mobile stroke units (STOP-MSU) is a phase II double-blind, randomised, placebo-controlled, multicentre, international investigator-led clinical trial, conducted within the estimand statistical framework.HypothesisIn patients with spontaneous ICH, treatment with tranexamic acid within 2 hours of onset will reduce haematoma expansion compared with placebo.Sample size estimatesA sample size of 180 patients (90 in each arm) would be required to detect an absolute difference in the primary outcome of 20% (placebo 39% vs treatment 19%) under a two-tailed significance level of 0.05. An adaptive sample size re-estimation based on the outcomes of 144 patients will allow a possible increase to a prespecified maximum of 326 patients.InterventionParticipants will receive 1 g intravenous tranexamic acid over 10 min, followed by 1 g intravenous tranexamic acid over 8 hours; or matching placebo.Primary efficacy measureThe primary efficacy measure is the proportion of patients with haematoma growth by 24±6 hours, defined as either ≥33% relative increase or ≥6 mL absolute increase in haematoma volume between baseline and follow-up CT scan.DiscussionWe describe the rationale and protocol of STOP-MSU, a phase II trial of tranexamic acid in patients with ICH within 2 hours from onset, based in participating mobile stroke units and emergency departments.

A RANDOMIZED CONTROLLED TRIAL OF CURCUMIN AND DICLOFENAC COMBINATION IN KNEE OSTEOARTHRITIS

Objective: The objective of the study was to evaluate pain relief and safety of the combination of curcumin and diclofenac versus diclofenac alone in the treatment of knee osteoarthritis (OA). Methods: 140 patients of knee OA meeting inclusion criteria were randomized to receive either curcumin 500 mg with diclofenac 50 mg twice daily or diclofenac 50 mg tablet al. one twice daily for 28 d. Patients were assessed at baseline, Day 14 and Day 28. Primary efficacy measure was severity of pain (VisualAnalogue Scale) at day 14 and day 28. Safety after treatment was evaluated by recording side effects and laboratory investigations. Results: Patients receiving curcumin plus diclofenac showed significantly superior improvement in severity of pain at each study visit (p<0.001) when compared to diclofenac. Adverse effects were significantly less in the curcumin plus diclofenac group (p<0.001). Conclusion: Combination of curcumin and diclofenac showed a significant improvement in pain on the basis of VAS when compared to diclofenac which may be due to the synergistic effect between curcumin and diclofenac

Agomelatine or placebo as adjunctive therapy to a mood stabiliser in bipolar I depression: Randomised double-blind placebo-controlled trial

BackgroundAdjunctive antidepressant therapy is commonly used to treat acute bipolar depression but few studies have examined this strategy.AimsTo examine the efficacy of agomelatine v. placebo as adjuncts to lithium or valproate in bipolar depression.MethodPatients who were currently depressed despite taking lithium or valproate for at least 6 weeks were randomised to treatment with agomelatine (n = 172) or placebo (n = 172) for 8 weeks of acute therapy and 44 weeks of continuation therapy (trial registration: ISRCTN28588282).ResultsNo significant differences in improvement of depressive symptoms were observed between the two groups either at 8 weeks or 52 weeks on the primary efficacy measure of change in Montgomery–Åsberg Depression Rating Scale scores from baseline to end-point. Adverse events including switches into mania/hypomania were low and similar in both groups.ConclusionsAgomelatine adjunctive therapy was not superior to placebo adjunctive therapy for acute bipolar depression.

FC03-04 - Lamotrigine treatment of acute alcohol hallucinosis comorbid depersonalizations disorders: A randomimized double-blind, placebo-controlled study

AimsWe compared the efficacy and safety of lamotrigine versus placebo for the treatment of acute alcohol hallucinosis comorbid depersonalization disorders.Methods10 days, randomized, double-blind, parallel study. A total of 40 patients with an ICD-10 diagnosis of acute alcohol hallucinosis comorbid depersonalization disorders were randomized to lamotrigine 300 mg/d (n = 40), or placebo (n = 40). The primary efficacy measure was the PANSS subscale for hallucinosis and Cambridge Depersonalization Scale (CDS).ResultsIamotrigine treated patients demonstrated a statistically significant greater improvement in PANSS subscale for hallucinosis and CDS than placebo-treated patients.ConclusionLamotrigine demonstrated greater efficacy than placebo in treatment of acute hallucinosis comorbid depersonalization disorders and was generally well tolerated.

Frovatriptan for the Acute Treatment of Migraine

Frovatriptan 2.5 mg has been investigated for the treatment of moderate or severe migraine attacks in six placebo-controlled, randomised controlled trials (RCTs). The mean headache relief (a decrease from moderate or severe to none or mild) was 43 % after frovatriptan and 24 % after placebo. The mean therapeutic gain (active minus placebo) was 19 % (95 % confidence interval 16–22 %). In one large comparative RCT, sumatriptan 100 mg was superior to frovatriptan 2.5 mg for headache relief at two hours (47 versus 37 %). In three cross-over RCTs in which the patients treated migraine attacks as early as possible, frovatriptan 2.5 mg was quite similar to zolmitriptan 2.5 mg, rizatriptan 10 mg and almotriptan 12.5 mg for preference – the primary efficacy measure. It is concluded that frovatriptan is not the triptan of first choice in established moderate to severe migraine attacks (based on systematic reviews and one comparative RCT). However, if the patients can treat their migraine attacks at the start of an attack (and are not triptan-resistant), then frovatriptan is a reasonable treatment choice among the triptans.

Olanzapine for the treatment of borderline personality disorder: variable dose 12-week randomised double-blind placebo-controlled study

BackgroundDespite the prevalence and clinical significance of borderline personality disorder, its treatment remains understudied.AimsTo evaluate treatment with variably dosed olanzapine in individuals with borderline personality disorder.MethodIn this 12-week randomised, double-blind trial, individuals received olanzapine (2.5–20 mg/day; n=155) or placebo (n=159) (trial registry: NCT00091650). The primary efficacy measure was baseline to end-point change on the Zanarini Rating Scale for Borderline Personality Disorder (ZAN–BPD) using last-observation-carried-forward methodology.ResultsBoth olanzapine and placebo groups showed significant improvements but did not differ in magnitude at end-point (76.56 v. 76.25, P=0.661). Response rates (50% reduction in ZAN–BPD) were 64.7% with olanzapine and 53.5% with placebo (P=0.062); however, time to response was significantly shorter for olanzapine (P=0.022). Weight gain was significantly greater (2.86 v. 70.35 kg, P50.001), with higher incidence of treatment-emergent abnormal high levels of prolactin for the olanzapine group.ConclusionsIndividuals treated with olanzapine and placebo showed significant but not statistically different improvements on overall symptoms of borderline personality disorder. The types of adverse events observed with olanzapine treatment appeared similar to those observed previously in adult populations.