Determining the optimal cholecalciferol dosing regimen in children with CKD: a randomized controlled trial

2020 ◽  
Author(s):  
Arpana Iyengar ◽  
Nivedita Kamath ◽  
Hamsa V Reddy ◽  
Jyoti Sharma ◽  
Jyoti Singhal ◽  
...  
Keyword(s):  
Randomized Controlled Trial ◽  
Controlled Trial ◽  
Fibroblast Growth Factor 23 ◽  
Glomerular Disease ◽  
Dosing Regimen ◽  
Open Label ◽  
Intensive Phase ◽  
Treatment Groups ◽  
Randomized Controlled ◽  
Multicenter Randomized Controlled Trial

Abstract Background and objectives The optimal treatment regimen for correcting 25-hydroxyvitamin D (25OHD) deficiency in children with chronic kidney disease (CKD) is not known. We compared cholecalciferol dosing regimens for achieving and maintaining 25OHD concentrations ≥30ng/ml in children with CKD stages 2-4. Design An open-label multicenter randomized controlled trial randomized children with 25OHD concentrations<30ng/ml in 1:1:1 to oral cholecalciferol 3,000 IU daily, 25,000 IU weekly, or 100,000 IU monthly for 3-months (maximum 3 intensive courses).In those with 25OHD ≥30ng/ml 1,000IU cholecalciferol daily (maintenance course) was given for up to 9 months. Primary outcome was achieving 25OHD≥30 ng/ml at end of intensive phase treatment. Results 90 children were randomized to daily(n = 30), weekly(n = 29) or monthly(n = 31) treatment groups. At end of intensive phase, 70/90(77.8%) achieved 25OHD ≥30ng/ml; 25OHD concentrations were comparable between groups (median 44.3, 39.4, and 39.3 ng/ml for daily, weekly, and monthly groups respectively; p = 0.24) with no difference between groups for time to achieve 25OHD ≥30ng/ml (p = 0.28). There was no change in calcium, phosphorus, and parathyroid hormone, but fibroblast growth factor 23(p = 0.002) and klotho(p = 0.001) concentrations significantly increased and were comparable in all treatment groups. Irrespective of dosing regimen, children with glomerular disease had 25OHD concentrations lower than non-glomerular disease (25.8 vs 41.8 ng/ml; p = 0.007). One child had 25OHD concentration of 134 ng/ml and 5.5% had hypercalcemia without symptoms of toxicity. Conclusion Intensive treatment with oral cholecalciferol as daily, weekly or monthly regimens achieved similar 25OHD concentrations between treatment groups without toxicity. Children with glomerular disease required higher doses of cholecalciferol compared to those with non-glomerular disease.

scholarly journals Efficacy and Safety of Inhaled Ciclesonide in Treating Patients With Asymptomatic or Mild COVID-19 in the RACCO Trial: Protocol for a Multicenter, Open-label, Randomized Controlled Trial (Preprint)

2020 ◽  
Author(s):  
Junko Terada-Hirashima ◽  
Manabu Suzuki ◽  
Yukari Uemura ◽  
Masayuki Hojo ◽  
Ayako Mikami ◽  
...  
Keyword(s):  
Randomized Controlled Trial ◽  
Treatment Group ◽  
Controlled Trial ◽  
Symptomatic Treatment ◽  
Open Label ◽  
Exacerbation Rate ◽  
Treatment Groups ◽  
Randomized Controlled ◽  
Computed Tomography Images ◽  
Study Results

BACKGROUND Currently, there are no specific effective treatments for SARS-CoV-2 infection; however, various COVID-19 treatment options are under investigation. It is vital to continue investigating the landscape of SARS-CoV-2–induced pneumonia and therapeutic interventions. OBJECTIVE This paper presents the protocol for a randomized controlled trial that aims to compare the pneumonia exacerbation rate between ciclesonide (ALVESCO; Teijin Pharma Limited) administration and symptomatic treatment in patients with COVID-19 and to determine the efficacy of ciclesonide. The secondary objectives are to investigate the safety of ciclesonide administration, changes in clinical and laboratory findings, and the number of viral genome copies of SARS-CoV-2 over time between the 2 groups. METHODS In this investigator-initiated, exploratory, prospective, multicenter, parallel-group, open-label, randomized controlled trial, a total of 90 patients diagnosed with COVID-19 will be recruited from 21 hospitals in Japan based on specific inclusion and exclusion criteria. Participants will be randomized either to the ciclesonide group, which will receive a 400-µg dose of ciclesonide 3 times per day over a 7-day period, or to the symptomatic treatment group. Both groups will receive antitussives and antipyretics as required. Data collection for various parameters will be conducted on days 1, 2, 4, 8, 22, and 29 to record baseline assessments and the findings over an extended period. Computed tomography images taken prior to drug administration and 1 week following treatment will be compared, and efficacy will be confirmed by checking for pneumonia exacerbation. Primary endpoint analysis will be performed using the Fisher exact test to determine statistically significant differences in the pneumonia exacerbation rate between the ciclesonide and symptomatic treatment groups. RESULTS The first trial participant was enrolled on April 3, 2020. Recruitment is expected to be completed on September 30, 2020, while follow-up assessments of all participants are expected to be completed by October 31, 2020. The study results will be published in a peer-reviewed scientific journal. CONCLUSIONS The RACCO (Randomized Ciclesonid COVID-19) study will provide definitive comparative effectiveness data and important clinical outcomes data between the ciclesonide and symptomatic treatment groups. If the hypotheses that pneumonia exacerbation rate reduction is more significant in the ciclesonide treatment group than in the symptomatic treatment group and that ciclesonide is safe for use are valid, ciclesonide will serve as an important therapeutic option for patients with COVID-19. CLINICALTRIAL Japan Registry of Clinical Trials jRCTs031190269; https://jrct.niph.go.jp/en-latest-detail/jRCTs031190269 INTERNATIONAL REGISTERED REPORT DERR1-10.2196/23830

scholarly journals Effect of rhG-CSF Combined With Decitabine Prophylaxis on Relapse of Patients With High-Risk MRD-Negative AML After HSCT: An Open-Label, Multicenter, Randomized Controlled Trial

2020 ◽  
Vol 38 (36) ◽  
pp. 4249-4259
Author(s):  
Lei Gao ◽  
Yanqi Zhang ◽  
Sanbin Wang ◽  
Peiyan Kong ◽  
Yi Su ◽  
...  
Keyword(s):  
Randomized Controlled Trial ◽  
High Risk ◽  
Cumulative Incidence ◽  
Controlled Trial ◽  
Open Label ◽  
Hematopoietic Stem ◽  
Randomized Controlled ◽  
Minimal Dose ◽  
Significant Difference ◽  
Multicenter Randomized Controlled Trial

PURPOSE Relapse is a major cause of treatment failure after allogeneic hematopoietic stem-cell transplantation (allo-HSCT) for high-risk acute myeloid leukemia (HR-AML). The aim of this study was to explore the effect of recombinant human granulocyte colony-stimulating factor (rhG-CSF) combined with minimal-dose decitabine (Dec) on the prevention of HR-AML relapse after allo-HSCT. PATIENTS AND METHODS We conducted a phase II, open-label, multicenter, randomized controlled trial. Two hundred four patients with HR-AML who had received allo-HSCT 60-100 days before randomization and who were minimal residual disease negative were randomly assigned 1:1 to either rhG-CSF combined with minimal-dose Dec (G-Dec group: 100 µg/m2 of rhG-CSF on days 0-5 and 5 mg/m2 of Dec on days 1-5) or no intervention (non–G-Dec group). The primary outcome was relapse after transplantation, and the secondary outcomes were chronic graft-versus-host disease (cGVHD), safety of the treatment, and survival. RESULTS The estimated 2-year cumulative incidence of relapse in the G-Dec group was 15.0% (95% CI, 8.0% to 22.1%), compared with 38.3% (95% CI, 28.8% to 47.9%) in the non–G-Dec group ( P < .01), with a hazard ratio (HR) of 0.32 (95% CI, 0.18 to 0.57; P < .01). There was no statistically significant difference between the G-Dec and non–G-Dec groups in the 2-year cumulative incidence of cGVHD without relapse (23.0% [95% CI, 14.7% to 31.3%] and 21.7% [95% CI, 13.6% to 29.7%], respectively; P = .82), with an HR of 1.07 (95% CI, 0.60 to 1.92; P = .81). After rhG-CSF combined with minimal-dose Dec maintenance, increasing numbers of natural killer, CD8+ T, and regulatory T cells were observed. CONCLUSION Our findings suggest that rhG-CSF combined with minimal-dose Dec maintenance after allo-HSCT can reduce the incidence of relapse, accompanied by changes in the number of lymphocyte subtypes.

scholarly journals Efficacy and Safety of Inhaled Ciclesonide in Treating Patients With Asymptomatic or Mild COVID-19 in the RACCO Trial: Protocol for a Multicenter, Open-label, Randomized Controlled Trial

10.2196/23830 ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. e23830
Author(s):  
Junko Terada-Hirashima ◽  
Manabu Suzuki ◽  
Yukari Uemura ◽  
Masayuki Hojo ◽  
Ayako Mikami ◽  
...  
Keyword(s):  
Randomized Controlled Trial ◽  
Treatment Group ◽  
Controlled Trial ◽  
Symptomatic Treatment ◽  
Open Label ◽  
Exacerbation Rate ◽  
Treatment Groups ◽  
Randomized Controlled ◽  
Computed Tomography Images ◽  
Study Results

Background Currently, there are no specific effective treatments for SARS-CoV-2 infection; however, various COVID-19 treatment options are under investigation. It is vital to continue investigating the landscape of SARS-CoV-2–induced pneumonia and therapeutic interventions. Objective This paper presents the protocol for a randomized controlled trial that aims to compare the pneumonia exacerbation rate between ciclesonide (ALVESCO; Teijin Pharma Limited) administration and symptomatic treatment in patients with COVID-19 and to determine the efficacy of ciclesonide. The secondary objectives are to investigate the safety of ciclesonide administration, changes in clinical and laboratory findings, and the number of viral genome copies of SARS-CoV-2 over time between the 2 groups. Methods In this investigator-initiated, exploratory, prospective, multicenter, parallel-group, open-label, randomized controlled trial, a total of 90 patients diagnosed with COVID-19 will be recruited from 21 hospitals in Japan based on specific inclusion and exclusion criteria. Participants will be randomized either to the ciclesonide group, which will receive a 400-µg dose of ciclesonide 3 times per day over a 7-day period, or to the symptomatic treatment group. Both groups will receive antitussives and antipyretics as required. Data collection for various parameters will be conducted on days 1, 2, 4, 8, 22, and 29 to record baseline assessments and the findings over an extended period. Computed tomography images taken prior to drug administration and 1 week following treatment will be compared, and efficacy will be confirmed by checking for pneumonia exacerbation. Primary endpoint analysis will be performed using the Fisher exact test to determine statistically significant differences in the pneumonia exacerbation rate between the ciclesonide and symptomatic treatment groups. Results The first trial participant was enrolled on April 3, 2020. Recruitment is expected to be completed on September 30, 2020, while follow-up assessments of all participants are expected to be completed by October 31, 2020. The study results will be published in a peer-reviewed scientific journal. Conclusions The RACCO (Randomized Ciclesonid COVID-19) study will provide definitive comparative effectiveness data and important clinical outcomes data between the ciclesonide and symptomatic treatment groups. If the hypotheses that pneumonia exacerbation rate reduction is more significant in the ciclesonide treatment group than in the symptomatic treatment group and that ciclesonide is safe for use are valid, ciclesonide will serve as an important therapeutic option for patients with COVID-19. Trial Registration Japan Registry of Clinical Trials jRCTs031190269; https://jrct.niph.go.jp/en-latest-detail/jRCTs031190269 International Registered Report Identifier (IRRID) DERR1-10.2196/23830

A multicenter randomized controlled trial to evaluate the efficacy of surgery vs. radiofrequency ablation for small hepatocellular carcinoma (SURF trial).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 4002-4002 ◽  
Author(s):  
Namiki Izumi ◽  
Kiyoshi Hasegawa ◽  
Yujiro Nishioka ◽  
Tadatoshi Takayama ◽  
Naoki Yamanaka ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Randomized Controlled Trial ◽  
Radiofrequency Ablation ◽  
Early Stage ◽  
Controlled Trial ◽  
Small Hepatocellular Carcinoma ◽  
Open Label ◽  
Randomized Controlled ◽  
Multicenter Randomized Controlled Trial

4002 Background: Surgery (SUR) and radiofrequency ablation (RFA) are both known to be effective therapy for treating patients with small oligonodular hepatocellular carcinoma (HCC), however there is only insufficient evidence about which therapy is more preferred approach. This randomized controlled trial was designed to prospectively compare the efficacy of SUR and RFA as the first approach to primary HCC. Methods: In this open-label trial undertaken at 49 hospital in Japan, we recruited patients having primary HCC with tumor foci numbering less than 3, each measuring 3 cm or less, Child-Pugh score of 7 or less, ages between 20 and 79 year. Before randomization, technical and liver functional feasibility for both treatment arms were confirmed by joint chart review by surgeons and hepatologists. Patients were then randomly assigned in a 1:1 ratio to undergo SUR or RFA, stratified by age, infection of hepatitis-C virus, number of tumors, tumor size and institution. The primary endpoint was recurrence free survival (RFS) and overall survival (OS). Results: Between April 2009 and August 2015, total 308 patients were enrolled to this trial. Because of ineligibility 15 patients were excluded, therefore 145 patients underwent SUR and 148 patients underwent RFA finally. There was no perioperative mortality. Under the median follow-up of 5 years, the 3-year RFS of patients underwent SUR and RFA was 49.8%, 47.7%, respectively (hazard ration [HR] 0.96, 95% CI 0.72-1.28; p = 0.793). OS will be analyzed and published after two years. Conclusions: SUR and RFA were both safe therapeutic approaches and provided equally RFS for early stage HCC smaller than 3 cm. Clinical trial information: UMIN000001795.

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