Efficacy and Safety of Intravenous Tenecteplase Bolus in Acute Ischemic Stroke: Results of Two Open-Label, Multicenter Trials.

BACKGROUND: Tenecteplase (TNK-tPA) is a promising third-generation plasminogen activator, because of its greater fibrin specificity and longer half-life than alteplase. There is a paucity of studies on intravenous thrombolysis using TNK-tPA in developing countries. The present study has been undertaken to compare the efficacy and safety of TNK-tPA with alteplase. METHODS: Two studies were conducted. Study I was an open-label, randomized study in which two doses of TNK-tPA (0.1 and 0.2 mg/kg) were compared. Study II was an open-label study in which TNK-tPA 0.2 mg/kg bolus was compared with historical controls. The primary endpoint for study I and study II was an improvement of ≥ 8 points or a score of 0 on the National Institutes of Health Stroke Scale (NIHSS) [major neurological improvement (MNI)] at 24 h. Secondary endpoints for both studies were neurological improvement as assessed using the NIHSS score, modified Rankin Scale (mRS) score and the Barthel Index (BI) on days 7, 30 and 90. Minimal disability was defined as an mRS score of 0 or 1 and good functional recovery as a BI score of 50-90. Safety was assessed by the proportion of patients having symptomatic intracranial hemorrhage (sICH) within 36 h and asymptomatic intracranial hemorrhage at 48 h after treatment. RESULTS: In study I, 20 patients received 0.1 mg/kg and 30 received 0.2 mg/kg TNK-tPA. There was no significant difference in MNI at 24 h between 0.1 and 0.2 mg/kg TNK-tPA doses. The patients given 0.2 mg/kg TNK-tPA had a significantly better 3-month outcome (minimal disability, p = 0.007). There was no sICH in study I. In study II, 62 patients (one lost to follow-up) received 0.2 mg/kg TNK-tPA. MNI was noted in ten patients (16.4%), 3-month minimal disability was noted in 37 patients (60.7%), and good functional recovery was seen in 33 patients (54.1%). sICH occurred in one patient, and four patients died. Pooled data of patients in study I and study II receiving 0.2 mg/kg TNK-tPA were compared with data from the historical National Institute of Neurological Disorders and Stroke (NINDS) trial. For comparison, the primary endpoint of the NINDS trial (improvement on NIHSS of ≥ 4 points or a score of 0 at 24 h) was taken. The primary endpoint though was not significantly different (58.2% vs. 47%, p = 0.08), but with TNK-tPA, greater neurological improvement, minimal disability (70.3 vs. 39%, p < 0.001) and good functional recovery (36.3 vs. 16%, p < 0.001) was noted at 3 months. There was a lower incidence of sICH (1.1 vs. 6.4%, p = 0.05) and lower 3-month mortality (5.5 vs. 17%, p = 0.01) noted with TNK-tPA compared with alteplase. CONCLUSIONS: Intravenous TNK-tPA 0.2 mg/kg administered within 3 hours of symptom onset seems to be well tolerated and effective option in patients with acute ischemic stroke. TRIAL REGISTRATION: Clinical Trials Registry-India, www.ctri.nic.in ; unique identifiers: CTRI/2009/091/000251 and CTRI/2015/02/005556.

The differential effects of core stabilization exercise regime and conventional physiotherapy regime on postural control parameters during perturbation in patients with movement and control impairment chronic low back pain.

BACKGROUND: The purpose of the present study was to examine the differential effect of core stability exercise training and conventional physiotherapy regime on altered postural control parameters in patients with chronic low back pain (CLBP). As heterogeneity in CLBP population moderates the effect of intervention on outcomes, in this study, interventions approaches were used based on sub-groups of CLBP. METHODS: This was an allocation concealed, blinded, sequential and pragmatic control trial. Three groups of participants were investigated during postural perturbations: 1) CLBP patients with movement impairment (n = 15, MI group) randomized to conventional physiotherapy regime 2) fifteen CLBP patients with control impairment randomized to core stability group (CI group) and 3) fifteen healthy controls (HC). RESULTS: The MI group did not show any significant changes in postural control parameters after the intervention period however they improved significantly in disability scores and fear avoidance belief questionnaire work score (P < 0.05). The CI group showed significant improvements in Fx, Fz, and My variables (p < 0.013, p < 0.006, and p < 0.002 respectively with larger effect sizes: Hedges's g > 0.8) after 8 weeks of core stability exercises for the adjusted p values. Postural control parameters of HC group were analyzed independently with pre and post postural control parameters of CI and MI group. This revealed the significant improvements in postural control parameters in CI group compared to MI group indicating the specific adaptation to the core stability exercises in CI group. Though the disability scores were reduced significantly in CI and MI groups (p < 0.001), the post intervention scores between groups were not found significant (p < 0.288). Twenty percentage absolute risk reduction in flare-up rates during intervention was found in CI group (95% CI: 0.69-0.98). CONCLUSIONS: In this study core stability exercise group demonstrated significant improvements after intervention in ground reaction forces (Fz, Mz; g > 0.8) indicating changes in load transfer patterns during perturbation similar to HC group. TRIAL REGISTRATION: UTRN095032158-06012009423714.