scholarly journals Effect of Combined Treatment with MLC601 (NeuroAiDTM) and Rehabilitation on Post-Stroke Recovery: The CHIMES and CHIMES-E Studies

2018 ◽  
Vol 46 (1-2) ◽  
pp. 82-88 ◽  
Author(s):  
Nijasri C. Suwanwela ◽  
Christopher L.H. Chen ◽  
Chun Fan Lee ◽  
Sherry H. Young ◽  
San San Tay ◽  
...  
Keyword(s):  
Treatment Effect ◽  
Treatment Time ◽  
Controlled Trial ◽  
Combined Treatment ◽  
Functional Independence ◽  
Stroke Recovery ◽  
Double Blind ◽  
Stroke Treatment ◽  
Rehabilitation Programs ◽  
Sustained Effects

Background and Purpose: MLC601 has been shown in preclinical studies to enhance neurorestorative mechanisms after stroke. The aim of this post hoc analysis was to assess whether combining MLC601 and rehabilitation has an effect on improving functional outcomes after stroke. Methods: Data from the CHInese Medicine NeuroAiD Efficacy on Stroke (CHIMES) and CHIMES-Extension (CHIMES-E) studies were analyzed. CHIMES-E was a 24-month follow-up study of subjects included in CHIMES, a multi-centre, double-blind placebo-controlled trial which randomized subjects with acute ischemic stroke, to either MLC601 or placebo for 3 months in addition to standard stroke treatment and rehabilitation. Subjects were stratified according to whether they received or did not receive persistent rehabilitation up to month (M)3 (non- randomized allocation) and by treatment group. The modified Rankin Scale (mRS) and Barthel Index were assessed at month (M) 3, M6, M12, M18, and M24. Results: Of 880 subjects in CHIMES-E, data on rehabilitation at M3 were available in 807 (91.7%, mean age 61.8 ± 11.3 years, 36% female). After adjusting for prognostic factors of poor outcome (age, sex, pre-stroke mRS, baseline National Institute of Health Stroke Scale, and stroke onset-to-study-treatment time), subjects who received persistent rehabilitation showed consistently higher treatment effect in favor of MLC601 for all time points on mRS 0–1 dichotomy analysis (ORs 1.85 at M3, 2.18 at M6, 2.42 at M12, 1.94 at M18, 1.87 at M24), mRS ordinal analysis (ORs 1.37 at M3, 1.40 at M6, 1.53 at M12, 1.50 at M18, 1.38 at M24), and BI ≥95 dichotomy analysis (ORs 1.39 at M3, 1.95 at M6, 1.56 at M12, 1.56 at M18, 1.46 at M24) compared to those who did not receive persistent rehabilitation. Conclusions: More subjects on MLC601 improved to functional independence compared to placebo among subjects receiving persistent rehabilitation up to M3. The larger treatment effect of MLC601 was sustained over 2 years which supports the hypothesis that MLC601 combined with rehabilitation might have beneficial and sustained effects on neuro-repair processes after stroke. There is a need for more data on the effect of combining rehabilitation programs with stroke recovery treatments.

scholarly journals CHInese Medicine NeuroAiD Efficacy on Stroke Recovery - Extension Study (CHIMES-E): A Multicenter Study of Long-Term Efficacy

2015 ◽  
Vol 39 (5-6) ◽  
pp. 309-318 ◽  
Author(s):  
Narayanaswamy Venketasubramanian ◽  
Sherry H. Young ◽  
San San Tay ◽  
Thirugnanam Umapathi ◽  
Annabelle Y. Lao ◽  
...  
Keyword(s):  
Chinese Medicine ◽  
Controlled Trial ◽  
Statistical Significance ◽  
Functional Independence ◽  
Stroke Recovery ◽  
Double Blind ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Time Points

Background: The CHInese Medicine NeuroAiD Efficacy on Stroke recovery (CHIMES) study was an international randomized double-blind placebo-controlled trial of MLC601 (NeuroAiD) in subjects with cerebral infarction of intermediate severity within 72 h. CHIMES-E (Extension) aimed at evaluating the effects of the initial 3-month treatment with MLC601 on long-term outcome for up to 2 years. Methods: All subjects randomized in CHIMES were eligible for CHIMES-E. Inclusion criteria for CHIMES were age ≥18, baseline National Institute of Health Stroke Scale of 6-14, and pre-stroke modified Rankin Scale (mRS) ≤1. Initial CHIMES treatment allocation blinding was maintained, although no further study treatment was provided in CHIMES-E. Subjects received standard care and rehabilitation as prescribed by the treating physician. mRS, Barthel Index (BI), and occurrence of medical events were ascertained at months 6, 12, 18, and 24. The primary outcome was mRS at 24 months. Secondary outcomes were mRS and BI at other time points. Results: CHIMES-E included 880 subjects (mean age 61.8 ± 11.3; 36% women). Adjusted OR for mRS ordinal analysis was 1.08 (95% CI 0.85-1.37, p = 0.543) and mRS dichotomy ≤1 was 1.29 (95% CI 0.96-1.74, p = 0.093) at 24 months. However, the treatment effect was significantly in favor of MLC601 for mRS dichotomy ≤1 at 6 months (OR 1.49, 95% CI 1.11-2.01, p = 0.008), 12 months (OR 1.41, 95% CI 1.05-1.90, p = 0.023), and 18 months (OR 1.36, 95% CI 1.01-1.83, p = 0.045), and for BI dichotomy ≥95 at 6 months (OR 1.55, 95% CI 1.14-2.10, p = 0.005) but not at other time points. Subgroup analyses showed no treatment heterogeneity. Rates of death and occurrence of vascular and other medical events were similar between groups. Conclusions: While the benefits of a 3-month treatment with MLC601 did not reach statistical significance for the primary endpoint at 2 years, the odds of functional independence defined as mRS ≤1 was significantly increased at 6 months and persisted up to 18 months after a stroke.

scholarly journals Prognostic Factors and Pattern of Long-Term Recovery with MLC601 (NeuroAiD™) in the Chinese Medicine NeuroAiD Efficacy on Stroke Recovery - Extension Study

2016 ◽  
Vol 43 (1-2) ◽  
pp. 36-42 ◽  
Author(s):  
Narayanaswamy Venketasubramanian ◽  
Chun Fan Lee ◽  
Sherry H. Young ◽  
San San Tay ◽  
Thirugnanam Umapathi ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Chinese Medicine ◽  
Treatment Effect ◽  
Treatment Time ◽  
Functional Independence ◽  
Stroke Recovery ◽  
Long Term Outcome ◽  
Nihss Score

Background: The Chinese Medicine NeuroAiD Efficacy on Stroke recovery - Extension (CHIMES-E) study is among the few acute stroke trials with long-term outcome data. We aimed to evaluate the recovery pattern and the influence of prognostic factors on treatment effect of MLC601 over 2 years. Methods: The CHIMES-E study evaluated the 2 years outcome of subjects aged ≥18 years with acute ischemic stroke, National Institutes of Health Stroke Scale (NIHSS) score 6-14, pre-stroke modified Rankin Scale (mRS) score ≤1 included in a multicenter, randomized, double-blind, placebo-controlled trial of MLC601 for 3 months. Standard stroke care and rehabilitation were allowed during follow-up with mRS score being assessed in-person at month (M) 3 and by telephone at M1, M6, M12, M18 and M24. Results: Data from 880 subjects were analyzed. There was no difference in baseline characteristics between treatment groups. The proportion of subjects with mRS score 0-1 increased over time in favor of MLC601 most notably from M3 to M6, thereafter remaining stable up to M24, while the proportion deteriorating to mRS score ≥2 remained low at all time points. Older age (p < 0.01), female sex (p = 0.06), higher baseline NIHSS score (p < 0.01) and longer onset to treatment time (OTT; p < 0.01) were found to be predictors of poorer outcome at M3. Greater treatment effect, with more subjects improving on MLC601 than placebo, was seen among subjects with 2 or more prognostic factors (OR 1.65 at M3, 1.78 at M6, 1.90 at M12, 1.65 at M18, 1.39 at M24), especially in subjects with more severe stroke or longer OTT. Conclusions: The sustained benefits of MLC601 over 2 years were due to more subjects improving to functional independence at M6 and beyond compared to placebo. Selection of subjects with poorer prognosis, particularly those with more severe NIHSS score and longer OTT delay, as well as a long follow-up period, may improve the power of future trials investigating the treatment effect of neuroprotective or neurorestorative therapies.

scholarly journals Effects of Vitamin D Supplementation on Surrogate Markers of Fertility in PCOS Women: A Randomized Controlled Trial

Nutrients ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 547
Author(s):  
Elisabeth Lerchbaum ◽  
Verena Theiler-Schwetz ◽  
Martina Kollmann ◽  
Monika Wölfler ◽  
Stefan Pilz ◽  
...  
Keyword(s):  
Vitamin D ◽  
Treatment Effect ◽  
Polycystic Ovary ◽  
Controlled Trial ◽  
Dehydroepiandrosterone Sulfate ◽  
Vitamin D Supplementation ◽  
Double Blind ◽  
Significant Treatment ◽  
Hydroxyvitamin D ◽  
Randomized Controlled

Vitamin D (VD) might play an important role in polycystic ovary syndrome (PCOS) and female fertility. However, evidence from randomized controlled trials (RCT) is sparse. We examined VD effects on anti-Müllerian hormone (AMH) and other endocrine markers in PCOS and non-PCOS women. This is a post hoc analysis of a single-center, double-blind RCT conducted between December 2011 and October 2017 at the endocrine outpatient clinic at the Medical University of Graz, Austria. We included 180 PCOS women and 150 non-PCOS women with serum 25-hydroxyvitamin D (25(OH)D) concentrations <75 nmol/L in the trial. We randomized subjects to receive 20,000 IU of VD3/week (119 PCOS, 99 non-PCOS women) or placebo (61 PCOS, 51 non-PCOS women) for 24 weeks. Outcome measures were AMH, follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol, dehydroepiandrosterone sulfate, and androstenedione. In PCOS women, we observed a significant treatment effect on FSH (mean treatment effect 0.94, 95% confidence interval [CI] 0.087 to 1.799, p = 0.031) and LH/FSH ratio (mean treatment effect −0.335, 95% CI −0.621 to 0.050, p = 0.022), whereas no significant effect was observed in non-PCOS women. In PCOS women, VD treatment for 24 weeks had a significant effect on FSH and LH/FSH ratio but no effect on AMH levels.

scholarly journals Randomised controlled general practice trial of sertraline, exposure therapy and combined treatment in generalised social phobia

2001 ◽  
Vol 179 (1) ◽  
pp. 23-30 ◽  
Author(s):  
S. Blomhoff ◽  
T. T. Haug ◽  
K. Hellström ◽  
I. Holme ◽  
M. Humble ◽  
...  
Keyword(s):  
General Practice ◽  
Social Phobia ◽  
Odds Ratio ◽  
Exposure Therapy ◽  
Controlled Trial ◽  
Combined Treatment ◽  
Practice Trial ◽  
Double Blind ◽  
Significant Difference ◽  
Double Blind Design

BackgroundNo controlled trial of treatment of generalised social phobia has been conducted in general practice.AimsTo examine the efficacy of sertraline or exposure therapy, administered alone or in combination in this setting.MethodStudy was of a randomised, double-blind design. Patients (n=387) received sertraline 50–150 mg or placebo for 24 weeks. Patients were additionally randomised to exposure therapy or general medical care.ResultsSertraline-treated patients were significantly more improved than non-sertraline-treated patients (χ2=12.53, P<0.001; odds ratio=0.534; 95% CI 0.347–0.835). No significant difference was observed between exposure— and non-exposure-treated patients (χ2=2.18, P=0.140; odds ratio=0.732; 95% CI 0.475–1.134). In the pairwise comparisons, combined sertraline and exposure (χ2=12.32; P<0.001) and sertraline (χ2=10.13; P=0.002) were significantly superior to placebo.ConclusionsSertraline is an effective treatment for generalised social phobia. Combined treatment with sertraline and exposure therapy, conducted by the general practitioner, may enhance the treatment efficacy in primary care.

scholarly journals Atorvastatin combined with dexamethasone in chronic subdural haematoma (ATOCH II): study protocol for a randomized controlled trial

Trials ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Rong Cai Jiang ◽  
Dong Wang ◽  
Shi Guang Zhao ◽  
Ren Zhi Wang ◽  
De Zhi Kang ◽  
...  
Keyword(s):  
Subdural Haematoma ◽  
Low Dose ◽  
Controlled Trial ◽  
Combined Treatment ◽  
Chronic Subdural Hematoma ◽  
Chronic Subdural Haematoma ◽  
Efficacy And Safety ◽  
Double Blind ◽  
Link Type ◽  
Haematoma Volume

Abstract Background Chronic subdural haematoma (CSDH) is a common condition in the elderly that often requires neurosurgical management. For small CSDH, evidence has emerged that statins may reduce haematoma volume and improve outcomes, presumably by reducing local inflammation and promoting vascular repair. We wish to extend this evidence in a study that aims to determine the efficacy and safety of atorvastatin combined with low-dose dexamethasone in patients with CSDH. Methods The second ATorvastatin On Chronic subdural Hematoma (ATOCH-II) study is a multi-centre, randomized, placebo-controlled, double-blind trial which aims to enrol 240 adult patients with a conservative therapeutic indication for CSDH, randomly allocated to standard treatment with atorvastatin 20 mg combined with low-dose dexamethasone (or matching placebos) daily for 28 days, and with 152 days of follow-up. The primary outcome is a composite good outcome defined by any reduction from baseline in haematoma volume and survival free of surgery at 28 days. Secondary outcomes include functional outcome on the modified Rankin scale (mRS) and modified Barthel Index at 28 days, surgical transition and reduction in haematoma volumes at 14, 28 and 90 days. Discussion This multi-centre clinical trial aims to provide high-quality evidence on the efficacy and safety of the combined treatment of atorvastatin and low-dose dexamethasone to reduce inflammation and enhance angiogenesis in CSDH. Trial registration ChiCTR, ChiCTR1900021659. Registered on 3 March 2019, http://www.chictr.org.cn/showproj.aspx?proj=36157.

Progression-free survival (PFS) and health-related quality of life (HRQoL) in AVAglio, a phase III study of bevacizumab (Bv), temozolomide (T), and radiotherapy (RT) in newly diagnosed glioblastoma (GBM).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 2005-2005 ◽  
Author(s):  
Roger Henriksson ◽  
Andrew Bottomley ◽  
Warren Mason ◽  
Frank Saran ◽  
Wolfgang Wick ◽  
...  
Keyword(s):  
Controlled Trial ◽  
Single Agent ◽  
Progression Free Survival ◽  
Functional Independence ◽  
Phase Iii ◽  
Newly Diagnosed ◽  
Double Blind ◽  
Patient Status ◽  
Related Quality ◽  
Eortc Qlq

2005^ Background: GBM has a high disease burden and poor prognosis, and impacts negatively on HRQoL. Symptomatic therapies for GBM, such as corticosteroids (CS), may impact patient status negatively Methods: AVAglio, a randomized, double-blind, placebo (P)-controlled trial in patients (pts) ≥18 yrs with newly diagnosed GBM, evaluated the addition of Bv or P (10mg/kg, q2w) to 6 wks of T (75mg/m2/d) + RT (2Gy, 5d/wk) followed by 28 treatment-free days, then 6 cycles of T (150–200 mg/m2/d, 5d q4w) with Bv or P (10 mg/kg, q2w), and then single-agent Bv or P (15 mg/kg, q3w) until disease progression (PD)/unacceptable toxicity. Co-primary endpoints were investigator-assessed PFS and overall survival. Secondary endpoints included HRQoL (EORTC QLQ-C30 and BN20, with 5 prespecified domains based on relevance in GBM). HRQoL time to definitive deterioration (TDD) was defined as time from randomization to ≥10 point deterioration from baseline with no subsequent improvement, PD, or death. Exploratory endpoints included KPS and CS use. Results: Baseline characteristics were well balanced. Bv significantly prolonged PFS (HR 0.64, 95% CI 0.55–0.74, p<0.0001; median 10.6 vs 6.2 mo) and delayed TDD in HRQoL compared with P (p<0.0001; Table). Functional independence (KPS ≥ 70%) was maintained during PFS in both arms (median Bv vs P: 9 vs 6 mo). Among pts on CS (≥ 2mg) at baseline, discontinuation (≥ 5 consecutive days) was more frequent with Bv than P (66% vs 47%). In pts off CS at baseline (< 2mg), time to CS initiation was significantly longer with Bv than P (HR 0.71, 95% CI 0.57–0.88; median 12.3 vs 3.7 mo). Conclusions: Addition of Bv to RT/T provided a clinically meaningful and statistically significant PFS improvement associated with stable/improved HRQoL and KPS, and reduced CS requirement. Clinical trial information: NCT00943826. [Table: see text]

scholarly journals Twelve-Month Outcomes of the AFFINITY Trial of Fluoxetine for Functional Recovery After Acute Stroke: AFFINITY Trial Steering Committee on Behalf of the AFFINITY Trial Collaboration

Stroke ◽  
2021 ◽  
Author(s):  
Graeme J. Hankey ◽  
Maree L. Hackett ◽  
Osvaldo P. Almeida ◽  
Leon Flicker ◽  
Gillian E. Mead ◽  
...  
Keyword(s):  
Acute Stroke ◽  
Functional Outcome ◽  
Bone Fractures ◽  
Controlled Trial ◽  
Trial Steering Committee ◽  
Stroke Recovery ◽  
Modified Rankin Scale ◽  
Unique Identifier ◽  
Double Blind ◽  
Trial Medication

Background and Purpose: The AFFINITY trial (Assessment of Fluoxetine in Stroke Recovery) reported that oral fluoxetine 20 mg daily for 6 months after acute stroke did not improve functional outcome and increased the risk of falls, bone fractures, and seizures. After trial medication was ceased at 6 months, survivors were followed to 12 months post-randomization. This preplanned secondary analysis aimed to determine any sustained or delayed effects of fluoxetine at 12 months post-randomization. Methods: AFFINITY was a randomized, parallel-group, double-blind, placebo-controlled trial in adults (n=1280) with a clinical diagnosis of stroke in the previous 2 to 15 days and persisting neurological deficit who were recruited at 43 hospital stroke units in Australia (n=29), New Zealand (4), and Vietnam (10) between 2013 and 2019. Participants were randomized to oral fluoxetine 20 mg once daily (n=642) or matching placebo (n=638) for 6 months and followed until 12 months after randomization. The primary outcome was function, measured by the modified Rankin Scale, at 6 months. Secondary outcomes for these analyses included measures of the modified Rankin Scale, mood, cognition, overall health status, fatigue, health-related quality of life, and safety at 12 months. Results: Adherence to trial medication was for a mean 167 (SD 48) days and similar between randomized groups. At 12 months, the distribution of modified Rankin Scale categories was similar in the fluoxetine and placebo groups (adjusted common odds ratio, 0.93 [95% CI, 0.76–1.14]; P =0.46). Compared with placebo, patients allocated fluoxetine had fewer recurrent ischemic strokes (14 [2.18%] versus 29 [4.55%]; P =0.02), and no longer had significantly more falls (27 [4.21%] versus 15 [2.35%]; P =0.08), bone fractures (23 [3.58%] versus 11 [1.72%]; P =0.05), or seizures (11 [1.71%] versus 8 [1.25%]; P =0.64) at 12 months. Conclusions: Fluoxetine 20 mg daily for 6 months after acute stroke had no delayed or sustained effect on functional outcome, falls, bone fractures, or seizures at 12 months poststroke. The lower rate of recurrent ischemic stroke in the fluoxetine group is most likely a chance finding. REGISTRATION: URL: http://www.anzctr.org.au/ ; Unique identifier: ACTRN12611000774921.

Flunarizine in stroke treatment (FIST): a double-blind, placebo-controlled trial in Scandinavia and the Netherlands

2009 ◽  
Vol 93 (1) ◽  
pp. 56-60 ◽  
Author(s):  
C. L. Franke ◽  
R. Palm ◽  
M. Dalby ◽  
H. C. Schoonderwaldt ◽  
L. Hantson ◽  
...  
Keyword(s):  
The Netherlands ◽  
Controlled Trial ◽  
Double Blind ◽  
Stroke Treatment ◽  
Double Blind Placebo

scholarly journals Atorvastatin combined with dexamethasone in chronic subdural haematoma (ATOCH II): study protocol for a randomised controlled trial

2020 ◽  
Author(s):  
Rong Cai Jiang ◽  
Dong Wang ◽  
Shi Guang Zhao ◽  
Ren Zhi Wang ◽  
De Zhi Kang ◽  
...  
Keyword(s):  
Subdural Haematoma ◽  
Low Dose ◽  
Controlled Trial ◽  
Combined Treatment ◽  
Chronic Subdural Hematoma ◽  
The Elderly ◽  
Chronic Subdural Haematoma ◽  
Efficacy And Safety ◽  
Double Blind ◽  
Haematoma Volume

Abstract Background Chronic subdural haematoma (CSDH) is a common condition in the elderly that often requires neurosurgical management. For small CSDH, evidence has emerged that statins may reduce haematoma volume and improve outcomes, presumably by reducing local inflammation and promoting vascular repair. We wish to extend this evidence in a study that aims to determine the efficacy and safety of atorvastatin combined with low-dose dexamethasone in patients with CSDH. Methods The second ATorvastatin On Chronic subdural Hematoma (ATOCH-II) study is a multi-center, randomized, placebo-controlled, double blind trial which aims to enroll 240 adult patients with a conservative therapeutic indication for CSDH, randomly allocated to standard treatment with atorvastatin 20 mg combined with low-dose dexamethasone (or matching placebos) daily for 28 days, and with 152 days of follow-up. The primary outcome is a composite good outcome defined by any reduction from baseline in haematoma volume and survival free of surgery at 28 days. Secondary outcomes include functional outcome on the modified Rankin scale (mRS) and modified Barthel Index at 28 days, surgical transition, and reduction in haematoma volumes at 14, 28 and 90 days. Discussion This multi-centre clinical trial aims to provide high-quality evidence on the efficacy and safety of the combined treatment of atorvastatin and low-dose dexamethasone to reduce inflammation and enhance angiogenesis in CSDH. Trial registration: ChiCTR, ChiCTR1900021659. Registered 3 March 2019, http://www.chictr.org.cn/showproj.aspx?proj=36157

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