scholarly journals Triple Therapy Prevention of Recurrent Intracerebral Disease Events Trial: Rationale, design and progress

2022 ◽  
pp. 174749302110686
Author(s):  
Craig S Anderson ◽  
Anthony Rodgers ◽  
H Asita de Silva ◽  
Sheila Ouriques Martins ◽  
Catharina JM Klijn ◽  
...  
Keyword(s):  
Triple Therapy ◽  
Cardiovascular Events ◽  
Active Sites ◽  
Antihypertensive Drugs ◽  
Standard Dose ◽  
Recurrent Stroke ◽  
Double Blind ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Simple Strategy

Background: Patients who suffer intracerebral hemorrhage (ICH) are at very high risk of recurrent ICH and other serious cardiovascular events. A single-pill combination (SPC) of blood pressure (BP) lowering drugs offers a potentially powerful but simple strategy to optimize secondary prevention. Objectives: The Triple Therapy Prevention of Recurrent Intracerebral Disease Events Trial (TRIDENT) aims to determine the effects of a novel SPC “Triple Pill,” three generic antihypertensive drugs with demonstrated efficacy and complementary mechanisms of action at half standard dose (telmisartan 20 mg, amlodipine 2.5 mg, and indapamide 1.25 mg), with placebo for the prevention of recurrent stroke, cardiovascular events, and cognitive impairment after ICH. Design: An international, double-blind, placebo-controlled, randomized trial in adults with ICH and mild-moderate hypertension (systolic BP: 130–160 mmHg), who are not taking any Triple Pill component drug at greater than half-dose. A total of 1500 randomized patients provide 90% power to detect a hazard ratio of 0.5, over an average follow-up of 3 years, according to a total primary event rate (any stroke) of 12% in the control arm and other assumptions. Secondary outcomes include recurrent ICH, cardiovascular events, and safety. Results: Recruitment started 28 September 2017. Up to 31 October 2021, 821 patients were randomized at 54 active sites in 10 countries. Triple Pill adherence after 30 months is 86%. The required sample size should be achieved by 2024. Conclusion: Low-dose Triple Pill BP lowering could improve long-term outcome from ICH.

Early Aneurysm Surgery and Preventive Therapy with Intravenously Administered Nimodipine: A Multicenter, Double-Blind, Dose-Comparison Study

Neurosurgery ◽  
1990 ◽  
Vol 26 (3) ◽  
pp. 458-464 ◽  
Author(s):  
Joachim M. Gilsbach ◽  
Hans J. Reulen ◽  
Bengt Ljunggren ◽  
Lennart Brandt ◽  
Hans v. Holst ◽  
...  
Keyword(s):  
Preventive Therapy ◽  
Neurological Dysfunction ◽  
Comparison Study ◽  
Double Blind ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Dose Comparison ◽  
Significant Difference ◽  
Low Incidence

Abstract A European, multicenter. prospective, randomized. double-blind, dose-comparison study on preventive therapy with intravenously administered nimodipine was performed to evaluate the efficacy and tolerability of two different doses: 2 and 3 mg/h. Two hundred four patients fulfilled the criteria for enrollment in the study; surgery within 72 hours after the last subarachnoid hemorrhage, and age between 16 and 72 years. All patients who had Hunt and Hess grades of I to III were operated upon: patients who had poor Hunt and Hess grades (IV-V) were operated on according to the surgeon's choice. This treatment regimen was associated with a low incidence of delayed neurological dysfunction with no significant difference between the two dosage groups: three patients (1.5%) remained severely disabled and two (1%) moderately disabled due to vasospasm with or without additional complications. Among the patients with Hunt and Hess grades of IV or V. the long-term outcome was favorable (good-fair) for 40% and unfavorable for 60%. Among the patients with grades of I to III, the long-term outcome was favorable for 89% and unfavorable for 11%.

Long-Term Outcome of Panic States During Double-Blind Treatment and After Withdrawal of Alprazolam and Placebo

1992 ◽  
Vol 4 (4) ◽  
pp. 251-258 ◽  
Author(s):  
Stephen Dager ◽  
Peter Roy-Byrne ◽  
Helen Hendrickson ◽  
Deborah Cowley ◽  
David Avery ◽  
...  
Keyword(s):  
Double Blind ◽  
Term Outcome ◽  
Long Term Outcome

scholarly journals Protein Biomarkers in Blood Reflect the Interrelationships between Stroke Outcome, Inflammation, Coagulation, Adhesion, Senescence and Cancer

2021 ◽  
Author(s):  
Georg Fuellen ◽  
Jan Böhmert ◽  
Larissa Henze ◽  
Daniel Palmer ◽  
Uwe Walter ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Cellular Senescence ◽  
Recurrent Stroke ◽  
Interaction Network ◽  
Stroke Severity ◽  
Protein Biomarkers ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Reactive Protein ◽  
Inflammatory Processes

The most important predictors for outcomes after ischemic stroke, that is, for health deterioration and death, are chronological age and stroke severity; gender, genetics and lifestyle / environmental factors also play a role. Of all these, only the latter can be influenced after the event, even though recurrent stroke may be prevented by antiaggregant/anticoagulant therapy, angioplasty of high-grade stenoses, and treatment of cardiovascular risk factors. Moreover, blood cell composition and protein biomarkers such as C-reactive protein or interleukins in serum are frequently considered as biomarkers of outcome. We surveyed protein biomarkers that were reported to be predictive for outcome after ischemic stroke, specifically considering biomarkers that predict long-term outcome (≥3 months) and that are measured over the first days following the event. We classified the protein biomarkers as immune‑inflammatory, coagulation-related, and adhesion-related biomarkers. Some of these biomarkers are closely related to cellular senescence and, in particular, to the inflammatory processes that can be triggered by senescent cells. Moreover, the processes that underlie inflammation, hypercoagulation and cellular senescence connect stroke to cancer, and biomarkers of cancer-associated thromboembolism, as well as of sarcopenia, overlap strongly with the biomarkers discussed here. Finally, we demonstrate that most of the outcome-predicting protein biomarkers form a close-meshed functional interaction network, suggesting that the outcome after stroke is partially determined by an interplay of molecular processes relating to inflammation, coagulation, cell adhesion and cellular senescence.

A Pilot Study for a Prospective, Randomized, Double-Blind Trial of the Influence of Anesthetic Depth on Long-Term Outcome

2014 ◽  
Vol 58 (5) ◽  
pp. 237-238
Author(s):  
Timothy G. Short ◽  
Kate Leslie ◽  
Douglas Campbell ◽  
Matthew T. V. Chan ◽  
Tomas Corcoran ◽  
...  
Keyword(s):  
Pilot Study ◽  
Double Blind Trial ◽  
Double Blind ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Anesthetic Depth ◽  
Blind Trial

Long-term outcome of molecular subgroups of GIST patients treated with standard-dose imatinib in the BFR14 trial of the French Sarcoma Group

2016 ◽  
Vol 52 ◽  
pp. 173-180 ◽  
Author(s):  
Anna Patrikidou ◽  
Julien Domont ◽  
Sylvie Chabaud ◽  
Isabelle Ray-Coquard ◽  
Jean-Michel Coindre ◽  
...  
Keyword(s):  
Standard Dose ◽  
Molecular Subgroups ◽  
Term Outcome ◽  
Long Term Outcome

Phase II-study of sequential high-dose-chemotherapy with paclitaxel, ifosfamide, carboplatin, etoposide( P-ICE) in patients with relapsed or refractory germ cell tumors (GCT).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 4552-4552
Author(s):  
Thomas Kegel ◽  
Franziska Cygon ◽  
Fabian Maximilian Meinert ◽  
Khaled Hammad ◽  
Frank Steinbach ◽  
...  
Keyword(s):  
Phase Ii ◽  
Standard Dose ◽  
Germ Cell Tumors ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Bone Marrow Toxicity ◽  
Good Tolerability ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Ecog Ps

4552 Background: High-dose chemotherapy (HD-CTx) is an active option for salvage chemotherapy in patients (pts) with refractory or relapsed GCT. All previous trials with HD-CTx used one or two cycles of high dose chemotherapy (CTx) including 2 or a maximum of 3 drugs. Another potentially more active option is the application of four sequential HD-CTx cycles (Schmoll et al, JCO 2003). Methods: We conducted a phase II trial of 1(-2) cycle(s) induction CTx with standard dose P-ICE (Paclitaxel 135mg/m² d1, Ifosfamide 1500mg/m² d1-3, Carboplatin 150mg/m² d1-3, Etoposide 150mg/m² d1-3), followed by 4 sequential cycles of HD-P-ICE (Paclitaxel 200mg/m² d1, Ifosfamide 3300mg/m² d1-3, Carboplatin 330mg/m² d1-3, Etoposide 330mg/m² d1-3). Eligibility criteria: relapse or progression under one or more induction CTx, ECOG PS (0-1), Creatinine-clearance > 30ml/min, adaequate liver function, measurable tumor or at least marker-elevation. Results: 37 pts entered the trial and 33 are evaluable (4 pts never received HD-CTx due to lack of stem cells (3) or medical reasons (1)). Prior CTx:1 (N = 26), 2 (N = 4), 3 (N = 3); primary extragonadal: 6; seminoma/ non-seminoma 5/28; ECOG-PS: 0 (19), 1 (14). Response rate: CR/NED 17 (51.5%), CR/NED/PR-/SD- with marker normalization 21 (63.6%), PD 12 (36.4%). DFS of CR/NED: median 59 (8-105) months; RFS of all favourable responders 60 (8-105) months, PFS total 46 (2-105) months. OS for all pts. 51 (6-105) months, OS Favourable Responders: 65 (23 – 105), Nonfavourable Responders: 11 (6-27) months,. Toxicity was tolerable without treatment related death, with mainly grade 4 bone-marrow toxicity and grade 2 mucositis and/or diarrhea. Conclusions: Sequential HD-CTx with one cycle of SD-P-ICE and four cycles HD-CTx is feasible with acceptable toxicity and favourable efficacy. Sequential HD-CTx using the four most active drugs might be a potentially option for this pts-population due to good tolerability, applicability and interesting long-term outcome. Comparison of the standard approach with 1 to 3 sequential high dose cycles of Carboplatin/Etoposide is ongoing (TIGER-Trial). Clinical trial information: EUDRA-CT: 2006-006004-11.

A Pilot Study for a Prospective, Randomized, Double-Blind Trial of the Influence of Anesthetic Depth on Long-Term Outcome

2014 ◽  
Vol 118 (5) ◽  
pp. 981-986 ◽  
Author(s):  
Timothy G. Short ◽  
Kate Leslie ◽  
Douglas Campbell ◽  
Matthew T. V. Chan ◽  
Tomas Corcoran ◽  
...  
Keyword(s):  
Pilot Study ◽  
Double Blind Trial ◽  
Double Blind ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Anesthetic Depth ◽  
Blind Trial

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.

Long-term outcome of sunitinib in metastatic renal cell carcinoma: Single center experience.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e15606-e15606
Author(s):  
Marco Maruzzo ◽  
Umberto Basso ◽  
Fable Zustovich ◽  
Pasquale Fiduccia ◽  
Antonella Brunello ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Kinase Inhibitor ◽  
Standard Dose ◽  
First Line ◽  
Term Outcome ◽  
Long Term Outcome

e15606 Background: The multi-target tyrosine-kinase inhibitor sunitinib has been widely used in first or subsequent lines of treatment for metastatic renal cell carcinoma (mRCC). Since results of registrative clinical trials may be overestimated due to patient selection, outcome data of sunitinib in the routine clinical practice are warranted. Methods: We retrospectively reviewed clinical data of all consecutive mRCC patients starting sunitinib from March 2006 to September 2012 at our Institution. Results: Eligible were 106 pts, median age 63 years (range 27-89), 70% males, 89% clear cell histology, 87% prior nephrectomy. Sunitinib was prescribed either as first (70%) or second or further line of treatment after cytokines or targeted therapies. Patients received a median of 8 sunitinib cycles (1-49). Median PFS and OS in the first line were 15.0 mo (95% CI= 9.8-20) and 35 mo. PFS and OS in the second or further line were 15 mo (11.7-18.2) and 25 mo. Motzer risk score retained its prognostic relevance both in the first and in the second of further line. Patients who received at least 4 cycles at standard dose (50 mg/d 4 wks on/2wks off) had a significantly better PFS and OS compared to patients who did not (PFS 23.0 vs 12.0 mo p=0.012, OS 49.0 vs 16.0 mo p=0.006). First line pts progressing within three months from starting sunitinib were 18.9% (primary refractory), while 25.7% pts were treated for more than 24 mo (long term responders). Grade 3 or 4 toxicities have been recorded in 35% of pts but only 7 pts (6.6%) discontinued the treatment due to unacceptable toxicities. Conclusions: Sunitinib is active and feasible in a broader population of mRCC pts, with apparently superior PFS and OS results compared to pivotal trials. Better management of drug toxicities, less strict criteria for radiological progression, and availability of further sequential treatments may explain such results. Pts receiving at least 4 full dose cycles achieved statistically significant better outcomes.

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