scholarly journals The Therapeutic Evaluation of Steroids in IgA Nephropathy Global (TESTING) Study: Trial Design and Baseline Characteristics

2021 ◽  
pp. 1-10
Author(s):  
Muh Geot Wong ◽  
Jicheng Lv ◽  
Michelle A. Hladunewich ◽  
Vivekanand Jha ◽  
Lai Seong Hooi ◽  
...  
Keyword(s):  
Iga Nephropathy ◽  
Kidney Failure ◽  
Trial Design ◽  
Low Dose ◽  
Treatment Algorithm ◽  
Renin Angiotensin System ◽  
Double Blind ◽  
Matching Placebo ◽  
Therapeutic Evaluation ◽  
Baseline Characteristics

<b><i>Introduction:</i></b> Despite optimal current care, up to 30% of individuals suffering from immunoglobulin A nephropathy (IgAN) will develop kidney failure requiring dialysis or kidney transplantation. The Therapeutic Evaluation of STeroids in IgA Nephropathy Global (TESTING) study was designed to assess the benefits and risks of steroids in people with IgAN. We report the trial design as well as the baseline characteristics of study participants. <b><i>Methods:</i></b> It is an investigator-initiated, multicenter, double-blind, placebo-controlled, randomized trial of individuals with kidney biopsy-confirmed IgAN, proteinuria ≥1 g/day, and an estimated GFR of 20–120 mL/min/1.73 m<sup>2</sup>, following at least 3 months of standard of care including maximum labelled (or tolerated) dose of renin-angiotensin system blockade. The original study design randomized participants 1:1 to oral methylprednisolone (0.6–0.8 mg/kg/day, maximum 48 mg/day) for 2 months, with subsequent weaning by 8 mg/day/month over 6–8 months, or matching placebo. The intervention was modified in 2016 (due to an excess of serious infection) to low-dose methylprednisolone (0.4 mg/kg/day, maximum 32 mg/day) for 2 months, followed by weaning by 4 mg/day/month over 6–9 months, or matching placebo. Participants recruited after 2016 also received prophylaxis against <i>Pneumocystis jirovecii</i> pneumonia during the first 12 weeks of treatment. <b><i>Results:</i></b> The study recruitment period extended from May 2012 to November 2019. By the time the excess of serious infections was observed, 262 participants had been randomized to the original full-dose treatment algorithm, and an interim analysis was reported in 2016. Subsequently, 241 additional participants were randomized to a revised low-dose protocol, for a total of 503 participants from China (373), India (78), Canada (24), Australia (18), and Malaysia (10). The mean age of randomized participants was 38, 39% were female, mean eGFR at randomization was 62.7 mL/min/1.73 m<sup>2</sup>, and mean 24-h urine protein 2.54 g. The primary endpoint is a composite of 40% eGFR decline from baseline or kidney failure (dialysis, transplantation, or death due to kidney disease), and participants will be followed until the primary outcome has been observed in at least 160 randomized participants. Analyses will also be made across predefined subgroups. Effects on eGFR slope and albuminuria will also be assessed overall, as well as by the steroid dosing regimen. <b><i>Conclusions:</i></b> The TESTING study (combined full and low dose) will define the benefits of corticosteroid use on major kidney outcomes, as well as the risks of therapy, and provide data on the relative effects of different doses, in individuals with high-risk IgAN.

scholarly journals Use of low-dose sulodexide in IgA nephropathy patients on renin–angiotensin system blockades

2012 ◽  
Vol 31 (3) ◽  
pp. 163-169 ◽  
Author(s):  
Byeong Yun Yang ◽  
Hee Seon Lee ◽  
Sang Heon Song ◽  
Ihm Soo Kwak ◽  
Soo Bong Lee ◽  
...  
Keyword(s):  
Iga Nephropathy ◽  
Low Dose ◽  
Renin Angiotensin System ◽  
Angiotensin System ◽  
Renin Angiotensin

Hypertension (HTN) in National Cancer Institute of Canada Clinical Trials Group study BR.24: A randomized, double-blind phase II trial of carboplatin (C) and paclitaxel (P) with either daily oral cediranib (CED), an inhibitor of vascular endothelial growth factor receptors, or placebo, in patients with advanced non-small cell lung cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 3527-3527
Author(s):  
R. A. Goodwin ◽  
L. Seymour ◽  
K. Ding ◽  
I. Gauthier ◽  
A. Le Maitre ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Cox Regression ◽  
Treatment Algorithm ◽  
Progression Free Survival ◽  
Angiogenesis Inhibitors ◽  
Double Blind ◽  
Minimal Impact ◽  
Kaplan Meier ◽  
History Of ◽  
Baseline Characteristics

3527 Background: CED 30 mg/d with C+P increased response rate (RR: 38 vs 16% p < 0.0001) and median progression free survival (PFS: 5.6 vs 5 m, hazard ratio [HR] 0.77) over C+P alone. HTN is a known effect of angiogenesis inhibitors (AI). For BR.24, we describe the incidence of HTN, effects on drug delivery, predictors of its development/worsening, and assess the predictive effect of HTN on efficacy. Methods: Pts received C+P plus either placebo (n =146) or CED (n = 148). HTN as an adverse event (HTN AE: defined as either new onset HTN, or worsening grade HTN in a previously hypertensive pt), was managed with a protocol-defined algorithm. Exploratory analyses characterized the relationship between HTN AE and baseline characteristics and treatment arm. Kaplan Meier curves summarized time to event outcomes and Cox regression models with time dependent covariates correlated HTN AE to outcomes. Results: Rate of pts with a history of HTN were similar: CED 26 %, placebo 33 %. CED pts had significantly higher HTN AE (any: 38 vs 12%, p < 0.0001; grade 3 or 4: 19 vs 2 %). With the treatment algorithm, HTN AE had minimal impact on drug delivery (1 pt interrupted C+P, 11 pts [3.7%] reduced /discontinued CED / placebo). Headache was the only other AE that correlated with HTN AE. Predictors of HTN AE included: CED arm (p < 0.0001), good ECOG (p = 0.02), female (p = 0.006), history of HTN (p = 0.06). CED pts with HTN AE had significantly higher RR (51.8 vs 32.6%, p = 0.025) and PFS (8.5 vs 5.1 m; HR 0.45, 95% CI 0.29 to 0.72, p = 0.0007); similar but not significant findings were observed with placebo (RR 35.3 vs 17.2%, p= 0.098; PFS 5.6 vs 4.9 m; HR 0.84, 95 % CI 0.45–1.54); the interaction term by treatment arm was not significant. Conclusions: CED pts had greater HTN AE, but this did not impact drug delivery. Certain baseline characteristics predicted HTN AE in all pts. Unexpectedly, development of on-study HTN predicted improved outcome in all pts, although to a greater extent for those on CED. Additional evaluation of the role of HTN AE as a predictor of efficacy of both AI and cytotoxics is warranted. [Table: see text]

A Double-Blind Comparison of Three Times Daily and Single Night Dosage of the Tricyclic Anti-Depressant Dothiepin

1974 ◽  
Vol 2 (1) ◽  
pp. 12-19 ◽  
Author(s):  
J B Pearce ◽  
W Linford Rees
Keyword(s):  
Single Dose ◽  
Dosage Regimen ◽  
Trial Design ◽  
Double Blind Trial ◽  
Double Blind ◽  
Matching Placebo ◽  
Symptoms Of Depression ◽  
Daily Dosage Regimen ◽  
Single Night ◽  
Blind Comparison

The study here presented was designed to evaluate the advantages of a once a day dosage of tricyclic anti-depressants as against a thrice daily dosage regimen using dothiepin (Prothiaden) and matching placebo capsules in a group comparative double-blind trial design. A total of sixty-two patients were admitted to the trial and were randomly allocated to one or other of the dosage regimes. Patients were assessed weekly for five weeks. More favourable results were achieved with patients taking the single dose nocturnally which was well tolerated in addition to being effective in relieving symptoms of depression. A number of possible advantages of this method of administration are discussed.

scholarly journals Statistical Analysis Plan for the Therapeutic Evaluation of Steroids in IgA Nephropathy Global Study (TESTING)

2021 ◽  
Author(s):  
Laurent Billot ◽  
Helen Monaghan ◽  
Muh Geot Wong ◽  
Vlado Perkovic
Keyword(s):  
Statistical Analysis ◽  
Iga Nephropathy ◽  
Controlled Trial ◽  
Renin Angiotensin System ◽  
Statistical Analysis Plan ◽  
Therapeutic Evaluation ◽  
Global Study ◽  
Risk Of Disease ◽  
Double Blinded

The TESTING (Therapeutic Evaluation of STeroids in IgA Nephropathy Global) study is a multicenter, double-blinded, randomised, placebo-controlled trial designed to evaluate the long-term efficacy and safety of oral methylprednisolone, on a background of routine renin angiotensin system (RAS) inhibitor therapy, in preventing kidney events in patients with IgA nephropathy with features suggestive of a high risk of disease progression. This statistical analysis plan (SAP) provides the details of all pre-specified analyses to be conducted at the end of the trial. The SAP was written by the trial statistician, chief investigator, study director and project manager and approved by the management committee.

scholarly journals Use of Low Dose Pregabalin for Attenuation of Hemodynamic Response to Laryngoscopy and Intubation in Treated Hypertensive Patients

2019 ◽  
Vol 2 (2) ◽  
pp. 215-219
Author(s):  
Puja Thapa ◽  
Sunita Panta ◽  
Mallika Rayamajhi ◽  
Santosh Khadka ◽  
Bishwo Ram Amatya ◽  
...  
Keyword(s):  
Low Dose ◽  
Hemodynamic Response ◽  
Sedation Scale ◽  
Double Blind ◽  
Hypertensive Patients ◽  
Randomised Study ◽  
Arterial Blood ◽  
Ramsay Sedation Scale ◽  
Dose Oral ◽  
Baseline Characteristics

Introduction: Laryngoscopy and tracheal intubation are two powerful noxious stimuli that can be potentially deleterious especially in hypertensive patients. This study evaluated the efficacy of low dose oral pregabalin used as a premedication for attenuation of this marked sympathetic response of airway instrumentation.Materials and Methods: This was a double-blind randomised study done at a tertiary level referral hospital. The trial was registered as UMIN-000037103 (https://www.umin.ac.jp/ctr/). Patients were randomly assigned into two groups. Placebo arm received multivitamin capsule and treatment arm received Cap. Pregabalin (75 mg), 60 minutes before the induction of general anesthesia. The level of preoperative sedation was assessed with the Ramsay Sedation Scale. Heart rate, systolic, diastolic and mean arterial blood pressure were monitored and recorded before and during induction, during laryngoscopy and 1, 3 and 5 minutes of intubation.Results: A total of 50 patients, 25 in each arm were enrolled. The baseline characteristics were comparable. SBP was significantly lower in the Pregabalin group than in Placebo at all the periods of recording, however, DBP and MAP decreased significantly during, after 1 and 3 minutes of laryngoscopy (p=0.001). Sedation was significantly better in the Pregabalin group with 86% in RSS 3 compared to 80% of a placebo arm in RSS2 (P <0.001).Conclusions: Premedication with a single oral dose of Pregabalin (75 mg) is effective for sedation and attenuation of hemodynamic response to direct laryngoscopy and endotracheal intubation in controlled hypertensive patients without any side effects.

scholarly journals Trial design and baseline characteristics of CaLIPSO: a randomized, double-blind placebo-controlled trial of SNF472 in patients receiving haemodialysis with cardiovascular calcification

2019 ◽  
Author(s):  
Antonio Bellasi ◽  
Paolo Raggi ◽  
Jordi Bover ◽  
David A Bushinsky ◽  
Glenn M Chertow ◽  
...  
Keyword(s):  
Coronary Artery ◽  
Aortic Valve ◽  
Trial Design ◽  
Agatston Score ◽  
Controlled Clinical Trial ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Maintenance Haemodialysis ◽  
Baseline Characteristics ◽  
Trial Participants

Abstract Background The objective of CaLIPSO, a Phase 2b, randomized, double-blind, placebo-controlled clinical trial, is to test the hypothesis that myo-inositol hexaphosphate (SNF472) attenuates the progression of cardiovascular calcification in patients receiving maintenance haemodialysis. Here we report the trial design and baseline characteristics of trial participants. Methods Adult patients on maintenance haemodialysis (≥6 months) with an Agatston coronary artery calcium score, as measured by a multidetector computed tomography scanner, of 100–3500 U were enrolled. Patients were stratified by Agatston score (100–<400, 400–1000 or >1000 U) and randomized in a 1:1:1 ratio to receive placebo, SNF472 300 mg or SNF472 600 mg administered intravenously three times weekly during each haemodialysis session. Results Overall, 274 patients were randomized. The mean age of trial participants was 63.6 (standard deviation 8.9) years and 39% were women. The coronary artery, aorta and aortic valve median (25th-75th percentile) Agatston scores at baseline were 730 U (315–1435), 1728 U (625–4978) and 103 U (31–262), respectively, and the median (25th–75th percentile) calcium volume scores at baseline were 666 (310–1234), 1418 (536–4052) and 107 (38–278), respectively. Older age and diabetes mellitus were associated with higher calcium scores at baseline. Conclusions The CaLIPSO trial enrolled patients on haemodialysis with pre-existent cardiovascular calcification to test the hypothesis that SNF472 attenuates its progression in the coronary arteries, aorta and aortic valve.

scholarly journals TRIFLUSAL VERSUS ASPIRIN IN SECONDARY STROKE PREVENTION:RESULTS OF TACIP STUDY

Stroke ◽  
2001 ◽  
Vol 32 (suppl_1) ◽  
pp. 329-329
Author(s):  
Jordi Matias-Guiu ◽  
Jose Ferro ◽  
Jose Alvarez-Sabin ◽  
Ferran Torres
Keyword(s):  
Low Dose ◽  
Total Mortality ◽  
Similar Efficacy ◽  
Cardiovascular Death ◽  
Secondary Stroke Prevention ◽  
Efficacy And Safety ◽  
Double Blind ◽  
End Point ◽  
Baseline Characteristics

73 TACIP was a multicentre, double-blind, randomised, parallel trial comparing the efficacy and safety of triflusal (600 mg/od) and ASA (325 mg/od) in patients who had a recent TIA or non disabling stroke. The primary end-point was the combined occurrence of non-fatal stroke, non-fatal AMI or cardiovascular death. Any of them separately was a secondary end-point, as well as total mortality, major systemic or cerebral hemorrhage and systemic thromboembolism. Forty-three centres in Spain and Portugal participated in the trial. A total of 2108 patients were evaluated with a mean follow-up of 31 months. There were no significant differences between both groups regarding to baseline characteristics. Main results were: The incidence of major and minor hemorrhages were higher in ASA than in triflusal group (24.5% vs 16.4%; p<0.001). Conclusion: Triflusal and low-dose ASA have a similar efficacy in secondary stroke prevention. Major and minor hemorrhages were significantly reduced by triflusal. Triflusal is a safer alternative to aspirin in the secondary prevention of stroke.

Sign in / Sign up

Export Citation Format

Share Document