ED90 of spinal 2-chloroprocaine 1% in ambulatory knee arthroscopy up to 45 min: a randomized biased-coin- up-and-down sequential allocation trial

2022 ◽  
pp. rapm-2021-103089
Author(s):  
Elsbeth J Wesselink ◽  
Seppe J Koopman ◽  
Rien van der Vegt ◽  
Peter M van de Ven ◽  
Jan P van der Aa ◽  
...  
Keyword(s):  
Hospital Discharge ◽  
Knee Arthroscopy ◽  
Final Analysis ◽  
Sensory Block ◽  
Complete Recovery ◽  
Open Label ◽  
Urine Retention ◽  
Quick Recovery ◽  
Smooth Flow ◽  
Biased Coin

BackgroundA short acting spinal anesthetic facilitates smooth flow since quick recovery of motor function will facilitate unassisted ambulation. The aim of this study was to estimate the effective dose (ED90) of intrathecal 2-chloroprocaine 1% in outpatient knee arthroscopy.MethodsTwo cohorts were included in two different hospitals. In cohort I, a randomized biased-coin up-and-down design with 40 patients was used to find the ED90. Four dose-levels of plain 2-chloroprocaine 1% were used: 25, 30, 35 and 40 mg. The identified primary outcome, the ED90, was validated in 50 patients in cohort II with an open label design. Secondary outcomes included time to complete recovery from motor and sensory block with spinal injection as time zero, peak sensory block level, urine retention and time until hospital discharge.ResultsForty patients were included in the final analysis in cohort I. The ED90 was estimated at 27.8 mg, successful spinal anesthesia was obtained in 38 patients (95%). Fifty patients were included in the final analysis in cohort II, 49 patients had successful anesthesia with a fixed round dose of 28 mg. In this Cohort, peak sensory block was T10/T11 (range: (L4–T4)). The median time to full recovery of the motor block was 60 min (45–60) and 90 min (75–105) for the sensory block. The mean time to hospital discharge was 2.9 hours (0.7).ConclusionThe ED90 of 2-chloroprocaine 1% in knee arthroscopy was estimated to be 27.8 mg. In an external population, the ED90 resulted in successful anesthesia in 98% of the patients (95% CI 89% to 100%).Trial registration numberNetherlands Trial Registry (NL6769).

Chloroprocaine versus prilocaine for spinal anesthesia in ambulatory knee arthroscopy: a double-blind randomized trial

2019 ◽  
Vol 44 (10) ◽  
pp. 944-949
Author(s):  
Elsbeth Wesselink ◽  
Godelief Janssen-van den Hurk ◽  
Rien van der Vegt ◽  
Cornelis Slagt ◽  
Jan van der Aa ◽  
...  
Keyword(s):  
Patient Satisfaction ◽  
Spinal Anesthesia ◽  
Hospital Discharge ◽  
Knee Arthroscopy ◽  
Sensory Block ◽  
Complete Recovery ◽  
Rapid Onset ◽  
Motor Blockade ◽  
Urine Retention ◽  
Double Blind

BackgroundIn ambulatory lower limb surgery, spinal anesthesia with rapid onset and a short duration of block is preferable. We hypothesized that the use of 2-chloroprocaine would be associated with a faster motor block recovery compared with prilocaine in knee arthroscopy. A difference of 15 min was considered clinically relevant.Methods150 patients were randomly allocated to receive intrathecally either 40 mg of 2-chloroprocaine or 40 mg of prilocaine. The primary outcome was the time to complete recovery from motor blockade. Secondary outcomes included time to full regression of sensory block, peak sensory block level, urine retention needing catheterization, time until hospital discharge, incidence of transient neurologic symptoms and patient satisfaction.ResultsTime to complete recovery from motor blockade was 15 min shorter for 2-chloroprocaine (median: 60 min; IQR: 60–82.5) than for prilocaine (median: 75 min; IQR: 60–90; p=0.004). 2-Chloroprocaine also resulted in faster full regression of sensory block (median: 120 min; IQR: 90–135 compared with median: 165 min; IQR: 135–190, p<0.001) and faster time to hospital discharge (mean difference: 57 min; 95% CI 38 to 77, p<0.001). Peak sensory block was higher in the 2-chloroprocaine group (median: T9; IQR: T6–T12 compared with median: T10; IQR: T8–T12, p<0.008). Patient satisfaction and urine retention needing catheterization were equal in both groups.ConclusionsIn knee arthroscopy, spinal anesthesia with 2-chloroprocaine results in a faster recovery of motor and sensory block, leading to quicker hospital discharge compared with prilocaine.Trial registration numberNTR6796.

An open-label, multicentre safety study of vemurafenib in patients with BRAFV600-mutant metastatic melanoma: final analysis and a validated prognostic scoring system

2019 ◽  
Vol 107 ◽  
pp. 175-185 ◽  
Author(s):  
James Larkin ◽  
Michael P. Brown ◽  
Ana M. Arance ◽  
Axel Hauschild ◽  
Paola Queirolo ◽  
...  
Keyword(s):  
Metastatic Melanoma ◽  
Scoring System ◽  
Final Analysis ◽  
Open Label ◽  
Safety Study

scholarly journals First-line treatment of chronic lymphocytic leukemia with ibrutinib plus obinutuzumab versus chlorambucil plus obinutuzumab: final analysis of the randomized, phase 3 iLLUMINATE trial

Haematologica ◽  
2022 ◽  
Author(s):  
Carol Moreno ◽  
Richard Greil ◽  
Fatih Demirkan ◽  
Alessandra Tedeschi ◽  
Bertrand Anz ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Final Analysis ◽  
Lymphocytic Leukemia ◽  
Small Lymphocytic Lymphoma ◽  
First Line ◽  
Open Label ◽  
Phase 3 ◽  
First Line Therapy ◽  
Line Therapy ◽  
Open Label Phase

iLLUMINATE is a randomized, open-label phase 3 study of ibrutinib plus obinutuzumab (n=113) versus chlorambucil plus obinutuzumab (n=116) as first-line therapy for patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma. Eligible patients were aged ≥65 years, or

Abstract 19427: Epidemiology and Outcomes of Out-of-hospital Cardiac Arrest in Qatar

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Furqan B Irfan ◽  
Zain A Bhutta ◽  
Tooba Tariq ◽  
Loua A Shaikh ◽  
Pregalathan Govender ◽  
...  
Keyword(s):  
Cardiac Arrest ◽  
Incidence Rate ◽  
Hospital Discharge ◽  
Middle Eastern ◽  
Cerebral Performance Category ◽  
Pulseless Electrical Activity ◽  
Final Analysis ◽  
National Registry ◽  
Bystander Cpr ◽  
Hospital Cardiac Arrest

Aim: There is a scarcity of population based studies on out-of-hospital cardiac arrest (OHCA) in the Middle East and the wider Asian region. This study describes the Epidemiology and outcomes of OHCA in Qatar, a Middle Eastern country. Methods: Data was extracted retrospectively from a national registry on all adult cardiac origin OHCA patients attended by Emergency Medical Services (EMS) in Qatar, from June 2012 - May 2013. Results: The annual crude incidence rate of cardiac origin OHCA attended by EMS was 23.5 per 100,000. The age-sex standardized incidence rate was 87.83 per 100,000 population. The annual sex-standardized incidence rate for males and females was 91.5 and 84.25 per 100,000 population respectively. Of 447 adult, cardiac origin OHCA patients included in the final analysis, most were male (n=360, 80.5%) with median age of 51 years (IQR = 39-66). Frequently observed nationalities of OHCA cases were Qatari (n=89, 19.9%), Indian (n=74, 16.6%) and Nepalese (n=52, 11.6%). Common initial cardiac arrest rhythms were asystole (n=301, 67.3%), ventricular fibrillation (n=82, 18.3%) and pulseless electrical activity (n=49, 11%). OHCA was unwitnessed (n=220, 49%) in nearly half of the cases while bystanders witnessed it in 170 (38%) patients. Bystander CPR was carried out in 92 (20.6%) of the cases. Of 187 (41.8%) patients who were given shocks, bystander defibrillation was delivered to 12 (2.7%) patients. Prehospital outcomes; 332 (74.3%) patients did not achieve return of spontaneous circulation (ROSC), 40 (8.9%) patients achieved unsustainable ROSC, 58 (13%) achieved ROSC till Emergency department (ED) handover and 5 patients achieved ROSC but rearrested again before reaching ED. Survival to hospital discharge occurred in 38 (8.5%) patients. Neurological outcomes were assessed utilizing Cerebral Performance Category [CPC] scores with a favorable CPC score of 1-2 at discharge in 27 (6%) patients, while 11 (2.5%) patients had a poor CPC score of 3-4. Of those with CPC score 1-2 at hospital discharge, 59% and 26% had CPC score 1-2, at 1 and 3 years follow-up respectively. Overall survival was 9.7%. Conclusion: Standardized rates are comparable to western countries, there are significant opportunities to improve outcomes, including better bystander CPR.

Analysis of the effect of crossover from placebo (PBO) to darolutamide (DARO) on overall survival (OS) benefit in the ARAMIS Trial.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 240-240
Author(s):  
Neal D. Shore ◽  
Karim Fizazi ◽  
Teuvo Tammela ◽  
Murilo Luz ◽  
Manuel Philco Salas ◽  
...  
Keyword(s):  
Treatment Effect ◽  
Safety Profile ◽  
Final Analysis ◽  
Phase Iii ◽  
Sensitivity Analyses ◽  
Primary Analysis ◽  
Open Label ◽  
Double Blind ◽  
Secondary Endpoints ◽  
The Impact

240 Background: DARO is a structurally distinct androgen receptor inhibitor approved for the treatment of non-metastatic castration-resistant prostate cancer (nmCRPC) based on significantly prolonged metastasis-free survival compared with PBO (median 40.4 vs 18.4 months; hazard ratio [HR] 0.41; 95% confidence interval [CI] 0.34–0.50; P < 0.0001) and a favorable safety profile in the phase III ARAMIS trial. Following unblinding at the primary analysis, crossover from PBO to DARO was permitted for the subsequent open-label treatment phase. Sensitivity analyses were performed to assess the effect of PBO–DARO crossover on OS benefit. Methods: Patients (pts) with nmCRPC receiving androgen deprivation therapy were randomized 2:1 to DARO (n = 955) or PBO (n = 554). In addition to OS, secondary endpoints included times to pain progression, first cytotoxic chemotherapy, first symptomatic skeletal event, and safety. The OS analysis was planned to occur after approximately 240 deaths, and secondary endpoints were evaluated in a hierarchical order. Iterative parameter estimation (IPE) and rank-preserving structural failure time (RPSFT) analyses were performed as pre-planned sensitivity analyses to adjust for the treatment effect of PBO–DARO crossover. The IPE method used a parametric model for the survival times and iteratively determined the model parameter describing the magnitude of the treatment effect, whereas a grid search and non-parametric log-rank test were used for the RPSFT analysis. The IPE and RPSFT analyses both generated a Kaplan–Meier curve for the PBO arm that predicts what would have been observed in the absence of PBO–DARO crossover. Results: After unblinding, 170 pts (30.7% of those randomized to PBO) crossed over from PBO to DARO; median treatment duration from unblinding to the final data cut-off was 11 months. Final analysis of the combined double-blind and open label periods was conducted after 254 deaths (15.5% of DARO and 19.1% of PBO pts) and showed a statistically significant OS benefit for DARO vs PBO (HR 0.69; 95% CI 0.53–0.88; P = 0.003). Results from the IPE (HR 0.66; 95% CI 0.51–0.84; P < 0.001) and RPSFT (HR 0.68; 95% CI 0.51–0.90; P = 0.007) analyses were similar to those from the intention-to-treat population, showing that the impact of PBO–DARO crossover was small. Additional analyses accounting for the effect of PBO–DARO crossover will be presented. The safety profile of DARO continued to be favorable at the final analysis, and discontinuation rates at the end of the double-blind period remained unchanged from the primary analysis (8.9% with DARO and 8.7% with PBO). Conclusions: Early treatment with DARO in men with nmCRPC is associated with significant improvement in OS regardless of pts crossing over from PBO to DARO. The safety profile of DARO remained favorable at the final analysis. Clinical trial information: NCT02200614.

Whole brain radiation therapy (WBRT) with or without oral topotecan (TPT) in patients (pts) with non-small cell lung cancer (NSCLC) with brain metastases: Final analysis of an open-label phase III study.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 2031-2031 ◽  
Author(s):  
Rodryg Ramlau ◽  
Jacek Jassem ◽  
Zsolt Papai-Szekely ◽  
Pierre Chabot ◽  
Philippe Legenne ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Population Analysis ◽  
Brain Lesion ◽  
Signs And Symptoms ◽  
Final Analysis ◽  
Primary Objective ◽  
Phase Iii ◽  
Smoking History ◽  
Hematologic Toxicity ◽  
Open Label

2031 Background: Brain metastases from NSCLC occur in ~ 20% of pts and if untreated are associated with a 1 to 2 month overall survival (OS). Pre-clinical studies show that TPT added to radiation results in a radiotherapy enhancement ratio of 1.4 to 1.6. This trial was designed to test the effect of TPT co-administered with WBRT on OS. Methods: Pts with NSCLC and at least one measurable brain lesion were eligible. 472 pts were randomized to WBRT (3 Gy/day x 10 days) or WBRT and TPT 1.1 mg/m2/day for 10 days. Stratification factors: number of brain metastases and recursive partitioning analysis (RPA) class. Two weeks following WBRT, systemic anti-cancer therapy could be restarted at the treating physician’s discretion. Results: 468 pts were in the modified ITT population; 235 pts (WBRT + TPT) and 233 pts (WBRT+ best supportive care [BSC]). Of the 235 pts administered WBRT + TPT, 91 also received TPT after WBRT. The treatment arms were balanced for gender, age and smoking history. Median daily TPT dose was 2.25 mg. The median OS in the TPT arm was not better than in the BSC alone arm; 4.0 months (95%CI 3.4,4.8) vs.3.6 months (95%CI 3.0, 4.0), respectively; HR 0.88 (0.73, 1.07), P=0.1862. In the ITT population analysis by stratification variables, RPA class (I vs. II/III) was significantly different (HR 0.59) whereas baseline brain lesions (1 vs >1) were not (HR 0.97). Complete response and overall response rates in the WBRT+ TPT were 10% and 27%, and with BSC 5% and 26%, respectively. There were no differences in time to response or neurologic signs and symptoms. All adverse events (AEs) were more frequent in the TPT arm (87% vs. 64%) as were AEs related to study treatment (57% vs. 21%), serious AEs (41% vs. 18%) and fatal AEs (5% vs. 0%). The AEs more frequently seen in the TPT arm were typical for TPT (hematologic toxicity, febrile neutropenia and diarrhea). Conclusions: The study did not achieve its primary objective. There was no difference in OS achieved by the addition of TPT to WBRT. AEs were more common in the TPT arm. Clinical trial information: NCT00390806.

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