Differences in the exposure to sunitinib in the immediate and deferred cytoreductive nephrectomy (CN) arms of the randomized controlled trial SURTIME.

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 703-703
Author(s):  
Yasmin Abu-Ghanem ◽  
Johannes V. Van Thienen ◽  
Christian U. Blank ◽  
Thomas Powles ◽  
Bertrand F. TOMBAL ◽  
...  
Keyword(s):  
Systemic Therapy ◽  
Drug Exposure ◽  
Controlled Trial ◽  
Dose Intensity ◽  
Duration Of Treatment ◽  
Intention To Treat ◽  
Number Of Patients ◽  
Metastatic Sites ◽  
Post Hoc ◽  
Treat Analysis

703 Background: SURTIME compared immediate CN followed by sunitinib 50mg/day (4/2 weeks on-off) 4 weeks after surgery (n=50) versus 3 cycles sunitinib followed by CN in the absence of progression and continued sunitinib 4 weeks after surgery (n=49). In the intention to treat analysis, the hazard ratio of the secondary endpoint overall survival (OS) favored deferred CN [0.57 (CI: 0.34–0.95, p=0.032)] with a median OS of 32.4 (CI: 14.5-65.3) versus only 15.0 months (CI: 9.3–29.5), following immediate CN. We investigated differences in exposure to systemic therapy between the two arms. Methods: Post-hoc exploratory analysis of number of patients receiving sunitinib, overall response rate (ORR) by RECIST 1.1, length of drug exposure and dose intensity in the immediate and deferred arm. Descriptive methods and 95% confidence intervals (CI) were used. Results: In the deferred arm, 97.7% (CI: 89.3-99.6; n=48) received sunitinib versus only 80% (CI: 66.9-88.7, n=40) in the immediate arm. Following immediate CN, 19.6% had confirmed progression at an interval CT scan 4 weeks after CN compared to baseline and 25% started with sunitinib > 4 weeks after surgery. At week 16, 46.0% had progressed at metastatic sites in the immediate CN arm versus 32.7% in the deferred arm, who had a per-protocol recommendation against nephrectomy. In the deferred arm, 83% completed 3 cycles sunitinib with 77.1% at >90%-120% relative dose intensity and an ORR of 29%, reducing the median sum of target lesions from 162 to 127 mm prior to planned CN.Of the patients who started with sunitinib in the immediate (n=40) or continued in the deferred arm after CN (n=29) median duration of treatment was 140 versus 351 days. Conclusions: With immediate CN fewer patients receive systemic therapy, which is administered later and shorter compared to the deferred approach. Starting systemic therapy with sunitinib leads to early and more profound control of the disease and identification of progression prior to planned CN which may translate into the observed survival benefit. Clinical trial information: NCT01099423.

scholarly journals Sex Differences in Spironolactone and the Active Metabolite Canrenone Concentrations and Adherence

Biomedicines ◽  
2022 ◽  
Vol 10 (1) ◽  
pp. 137
Author(s):  
Laura E. J. Peeters ◽  
Leonardien K. Tjong ◽  
Wim J. R. Rietdijk ◽  
Teun van Gelder ◽  
Birgit C. P. Koch ◽  
...  
Keyword(s):  
Sex Differences ◽  
Resistant Hypertension ◽  
Active Metabolite ◽  
Drug Exposure ◽  
Antihypertensive Drugs ◽  
Controlled Trial ◽  
Linear Regression Models ◽  
Blood Concentrations ◽  
Males And Females ◽  
Post Hoc

We aim to investigate sex differences in blood concentrations of spironolactone and the active metabolite canrenone in resistant hypertension patients. Furthermore, sex differences in adherence for spironolactone and other antihypertensive drugs (AHDs) were studied. The patients in this post hoc study had all participated in a single-blind randomized controlled trial called RHYME-RCT (Dutch Trial Register, NL6736). Concentrations in blood of several AHDs were assessed in RHYME-RCT to investigate adherence to treatment. This allowed for a comparison of drug exposure to spironolactone and canrenone between males and females. In linear regression models, no statistically significant sex differences (N = 35) in spironolactone (B =−10.23, SE = 7.92, p = 0.206) or canrenone (B = 1.24, SE = 10.96, p = 0.911) concentrations after adjustment for dose and time between sampling and intake were found. Furthermore, no statistically significant differences in non-adherence to spironolactone were found between sexes (N = 54, male 15% vs. female 38%, p = 0.100), but non-adherence to spironolactone was associated with non-adherence to other AHDs (p ≤ 0.001). Spironolactone and canrenone concentrations were not different between males and females with resistant hypertension. Although not statistically significant, females were twice as likely to be non-adherent to spironolactone compared to males, and thereby also more likely to be non-adherent to other AHDs.

scholarly journals Effect of manual therapy in patients with hemophilia and ankle arthropathy: a randomized clinical trial

2019 ◽  
Vol 34 (1) ◽  
pp. 111-119 ◽  
Author(s):  
Elena Donoso-Úbeda ◽  
Javier Meroño-Gallut ◽  
José Antonio López-Pina ◽  
Rubén Cuesta-Barriuso
Keyword(s):  
Manual Therapy ◽  
Joint Pain ◽  
Controlled Trial ◽  
Control Group ◽  
Load Bearing ◽  
Intention To Treat ◽  
Joint Health ◽  
Experimental Group ◽  
Treat Analysis

Objective: The aim of this study was to evaluate the effects of a manual therapy using fascial therapy on joint bleeding, joint pain and joint function in patients with hemophilic ankle arthropathy. Setting: Hemophilia patient associations. Design: Randomized, controlled trial, multicenter and intention-to-treat analysis. Participants: A total of 65 patients with hemophilic ankle arthropathy. Intervention: The experimental group ( n = 33) received one fascial therapy session per week for three weeks. The control group ( n = 32) received no treatment. Outcome measure: The primary outcome was frequency of joint bleeding measured using self-reporting. Secondary outcomes were joint pain (under load-bearing and non-load-bearing conditions) measured using the visual analog scale; joint condition was measured using the Hemophilia Joint Health Score. Outcomes were measured at baseline, posttreatment and after five months of follow-up. Results: Improvements in the frequency joint bleeding at T0, T1 and T2 were significantly higher in the experimental group (T0: mean (SD) = 1.56 (1.30); T1: mean (SD) = 0.00 (0.00); T2: mean (SD) = 0.27 (0.57)) compared to the control group (T0: mean (SD) = 1.70 (1.78); T1: mean (SD) = 0.05 (0.21); T2: mean (SD) = 0.58 (0.85)). Mean improvement of joint state after the study period was 1.74 points (±1.66) for patients in the experimental group, while the control group exhibited a joint deterioration with 0.43 points (±0.85). Ankle joint pain under load-bearing and non-load-bearing conditions improved in the experimental group with −1.72 (±1.86) and −0.50 (±1.39) points, respectively. Conclusion: The study showed that fascial therapy is favorable for patients with hemophilic ankle arthropathy.

scholarly journals The effectiveness of the Volunteer Family Connect Program in supporting vulnerable families: A randomised controlled trial intention-to-treat analysis of primary outcome variables (Preprint)

2018 ◽  
Author(s):  
Rebekah Grace ◽  
Kelly Baird ◽  
Emma Elcombe ◽  
Vana Webster ◽  
Jacqueline Barnes ◽  
...  
Keyword(s):  
Young Children ◽  
Home Visiting ◽  
Controlled Trial ◽  
Intervention Group ◽  
Parenting Competence ◽  
Community Connectedness ◽  
Intention To Treat ◽  
Vulnerable Families ◽  
Secondary Outcomes ◽  
Treat Analysis

BACKGROUND Volunteer home visiting is a widely adopted community-based approach to supporting families by linking isolated or vulnerable families with community volunteers. This study seeks to robustly evaluate the effectiveness of this model of support for families with young children. OBJECTIVE This paper reports the intention-to-treat analysis of primary and secondary outcomes for a pragmatic randomized controlled trial (RCT) of the Volunteer Family Connect intervention, a volunteer home visiting program designed to support families with young children who experience social isolation or a lack of parenting confidence and skills. METHODS The RCT was conducted across seven sites in Australia. Overall, 341 families were recruited: 169 intervention (services as usual + volunteer home visiting) and 172 control (services as usual) families. Intervention families received the program for 3-12 months. Participants were invited to complete six data collection points over a 15-month period. Primary outcomes were community connectedness and parenting competence. Secondary outcomes included parent physical and mental health, general parent wellbeing, parent empowerment, the sustainability of family routines, and the parent-child relationship. RESULTS The intervention group demonstrated significant improvement compared to the control group in both of the primary outcomes. They were significantly more like to report improvements in the guidance available to them as measured by the Social Provisions Scale, a key measure of community connectedness and scores on the Parenting Sense of Competence Scale were significantly in favour of the intervention group. Intervention families also reported significantly higher wellbeing, and were significantly more likely to feel that life was improving. A number of positive trends were also evident within the findings. CONCLUSIONS The Volunteer Family Connect intervention was considered to be an effective intervention for improving the community connectedness and parenting competence of families with young children. CLINICALTRIAL Australian New Zealand Clinical Trial Registry (Trial ID: ACTRN12616000396426).

Presenting a randomised controlled trial

2013 ◽  
Author(s):  
Janet L. Peacock ◽  
Sally M. Kerry
Keyword(s):  
Randomised Controlled Trial ◽  
Controlled Trial ◽  
Consort Statement ◽  
Intention To Treat ◽  
The Consort Statement ◽  
Randomised Controlled ◽  
Treat Analysis

Chapter 12 covers presenting a randomised controlled trial, including the CONSORT statement and checklist, intention to treat analysis, and presenting trials with other designs.

scholarly journals The Incidence of Postoperative Seizures Following Treatment of Postinfectious Hydrocephalus in Ugandan Infants: A Post Hoc Comparison of Endoscopic Treatment vs Shunt Placement in a Randomized Controlled Trial

Neurosurgery ◽  
2019 ◽  
Vol 85 (4) ◽  
pp. E714-E721 ◽  
Author(s):  
Maria Punchak ◽  
Edith Mbabazi Kabachelor ◽  
Michael Ogwal ◽  
Esther Nalule ◽  
Joyce Nalwoga ◽  
...  
Keyword(s):  
Controlled Trial ◽  
Bivariate Analysis ◽  
Third Ventriculostomy ◽  
Published Data ◽  
Intention To Treat ◽  
Kaplan Meier ◽  
Significant Difference ◽  
Postoperative Seizure ◽  
Post Hoc

Abstract BACKGROUND There are currently no published data directly comparing postoperative seizure incidence following endoscopic third ventriculostomy (ETV), with/without choroid plexus cauterization (CPC), to that for ventriculoperitoneal shunt (VPS) placement. OBJECTIVE To compare postoperative epilepsy incidence for ETV/CPC and VPS in Ugandan infants treated for postinfectious hydrocephalus (PIH). METHODS We performed an exploratory post hoc analysis of a randomized trial comparing VPS and ETV/CPC in 100 infants (<6 mo old) presenting with PIH. Minimum follow-up was 2 yr. Variables associated with and the incidence of postoperative epilepsy were compared (intention-to-treat) using a bivariate analysis. Time to first seizure was compared using the Kaplan–Meier method, and the relative risk for the 2 treatments was determined using Mantel-Haenszel hazard ratios. RESULTS Seizure incidence was not related to age (P = .075), weight (P = .768), sex (P = .151), head circumference (P = .281), time from illness to hydrocephalus onset (P = .973), or hydrocephalus onset to treatment (P = .074). Irritability (P = .027) and vision deficit (P = .04) were preoperative symptoms associated with postoperative seizures. Ten (10%) patients died, and 20 (20%) developed seizures over the follow-up period. Overall seizure incidence was 9.4 per 100 person-years (9.4 and 9.5 for ETV/CPC and VPS, respectively; P = .483), with no significant difference in seizure risk between groups (hazard ratio, 1.02; 95% CI: 0.42, 2.45; P = .966). Mean time to seizure onset was 8.5 mo for ETV/CPC and 11.2 mo for VPS (P = .464). As-treated, per-protocol, and attributable-intervention analyses yielded similar results. CONCLUSION Postoperative seizure incidence following treatment of PIH was 20% within 2 yr, regardless of treatment modality.

scholarly journals Propofol and Midazolam versus Propofol Alone for Sedation following Coronary Artery Bypass Grafting: A Randomized, Placebo-controlled Trial

2002 ◽  
Vol 30 (2) ◽  
pp. 171-178 ◽  
Author(s):  
B. Walder ◽  
A. Borgeat ◽  
P. M. Suter ◽  
J. A. Romand
Keyword(s):  
Mechanical Ventilation ◽  
Placebo Group ◽  
Low Dose ◽  
Controlled Trial ◽  
Artery Bypass ◽  
Bypass Grafting ◽  
Cumulative Number ◽  
Intention To Treat ◽  
Midazolam Group ◽  
Number Of Patients

The aim was to compare the efficacy and side-effects of propofol combined with a constant, low dose of midazolam versus propofol alone for sedation. In a prospective, randomized and double-blinded study, 60 male patients scheduled for elective coronary bypass grafting were enrolled. Postoperatively, patients were stratified to receive either a continuous intravenous infusion of midazolam 1 mg/h or placebo. Target Ramsay sedation score was 3 to 5 corresponding to conscious sedation. An intention-to-treat design for propofol was performed to reach target sedation. Efficacy of sedation was statistically significantly higher in the group midazolam+intention-to-treat with propofol compared with the group placebo+intention-to-treat with propofol (91% vs 79%; P=0.0005). Nine of 27 patients in the midazolam group (33.4%) and nine of 26 patients in the placebo group (34.6%) needed no supplementary propofol. Weaning time from mechanical ventilation was longer in the midazolam group whether or not they required supplemental propofol when compared with placebo group (all: 432±218 min vs 319±223 min; P=0.04; supplementary propofol: 424±234 min vs 265±175 min; P=0.03). The cumulative number of patients remaining intubated was significantly higher in the group midazolam+propofol compared with the group placebo+propofol (P=0.03). In conclusion, target sedation is reached slightly more often by the co-administration of propofol and a low dose of midazolam, but weaning time from mechanical ventilation is prolonged by the co-administration of propofol and a low dose of midazolam.

Simplified gemcitabine and platin regimen for NSCLC to be used in the neoadjuvant setting

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 17155-17155
Author(s):  
G. Cartei ◽  
S. Binato ◽  
C. Sacco ◽  
S. Scalone ◽  
R. Ceravolo ◽  
...  
Keyword(s):  
Liver Function ◽  
Neoadjuvant Therapy ◽  
Hospital Admissions ◽  
Dose Intensity ◽  
Day Hospital ◽  
Normal Kidney ◽  
Intention To Treat ◽  
The Third ◽  
Kidney Liver ◽  
Treat Analysis

17155 Background: Platin (P) salts and Gemcitabine (G) are used for NSCLC. GP regimens frequently included G on day 1, 8 and 15; P on day 2; every 28 days. However, the third G dose often is omitted because of myelo-toxicity, with a consistent no respect of the intended drugs’ doses. We devised a simplified regimen, based on two Day-Hospital admissions per cycle (c), with G on day 1 and 8; P after G on day 8; every 21 days. Aim of study: a high RR within the first 3 c.s for a GP regimen for neoadjuvant therapy. Methods: This prospective, multi-centre investigation included G (1500 mg/m2) on day 1 and 8, and P (100 mg/m2) on day 8 immediately following G, on a 3-weeks-c. Eligible criteria: age 18 to 75 years, NSCLC histologically, no previous chemotherapy, KPS 50%, WBC ≥ 4.0 × 109/L, platelet ≥100 × 109/L and normal kidney-liver function. QoL evaluation: 46 out of 95 valuable patients. Restaging procedures: repeated 3 and 6 c.s. Results: Out of 105 patients, 95 had at least 3 c.s and 59 of them had further 3 c.s. Myelo-toxicity ≥ G3 was mainly neuthropoenia, easily amenable with symptomatic and GCSF therapies; PNS toxicity occurred in 17.9% of patients. QoL was ameliorated (p < 0.05). Therapy was tolerable; gave RR was 52.3% after 3 c.s (Intention-to-treat analysis) and 57.9% in 95 valuable patients after at least 3 therapy c.s. In the 95 valuable patients over the first 42 days, i.e. after 2 c.s and just before the third c., 10 c.s out of 190 were delayed by one week, with a dose intensity reduction of 5.29%. Conclusions: This two Day-Hospital admissions regimen is at least as good as more complex GP regimens, with an appreciable RR after 3c.s; it may be proponed in the neoadjuvant setting. Acknowledgments: Present work was part of studies program of, and partly supported by, AOI (Associazione Oncologia Italiana, Padova, Italy). No significant financial relationships to disclose.

scholarly journals 117. Adjunctive Daptomycin in the Treatment of staphylococcus Aureus Bacteremia

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S187-S187
Author(s):  
Matthew P Cheng ◽  
Alexander Lawandi ◽  
Guillaume Butler-Laporte ◽  
Samuel De L’Etoile-Morel ◽  
Katryn Paquette ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Median Duration ◽  
Controlled Trial ◽  
Standard Of Care ◽  
Absolute Difference ◽  
Double Blind ◽  
Intention To Treat ◽  
Care Treatment ◽  
Standard Of Care Treatment ◽  
Treat Analysis

Abstract Background Bloodstream infections (BSI) caused by methicillin-susceptible Staphylococcus aureus (MSSA) are associated with significant morbidity and mortality. The objective of our study was to determine whether daptomycin given in combination with an anti-staphylococcal beta-lactam improved outcomes in MSSA BSI. Methods A randomized, double blind, placebo-controlled trial was performed at two academic hospitals in Montreal, Canada. Patients ≥ 18 years of age with MSSA BSI receiving either cefazolin or cloxacillin monotherapy were considered for inclusion. In addition to the standard of care treatment, participants received a 5-day course of adjunctive daptomycin or placebo. The primary outcome was the duration of MSSA BSI in days. Results Of 318 participants screened, 115 were enrolled and 104 were included in the intention to treat analysis (median age 67 years; 34.5% female). The median duration of bacteremia was 2.04 days among patients who received daptomycin versus 1.65 days in those who received placebo (absolute difference 0.39 days, p=0.40). A modified intention to treat analysis involving participants who remained bacteremic at the time of enrollment found a median duration of bacteremia of 3.06 days among patients who received daptomycin versus 3.0 days in those who received placebo (absolute difference 0.06 days, p=0.77). Ninety-day mortality in the daptomycin arm was 18.9% vs. 17.7% in the placebo arm (p=1.0). There were no significant differences in the proportion of patients who developed renal failure, hepatotoxicity, or rhabdomyolysis between groups. Conclusion Among patients with MSSA BSI, the administration of adjunctive daptomycin therapy to standard of care treatment did not shorten the duration of bacteremia. Disclosures All Authors: No reported disclosures

Sign in / Sign up

Export Citation Format

Share Document