scholarly journals A Prospective, Double-Blind, Randomized, Placebo-Controlled, Crossover Study Using an Orally Administered Oxalate Decarboxylase (OxDC)

Kidney360 ◽  
2020 ◽  
Vol 1 (11) ◽  
pp. 1284-1290
Author(s):  
Emily Quintero ◽  
Victoria Yvonne Bird ◽  
Howard Liu ◽  
Gary Stevens ◽  
Alan S. Ryan ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Adverse Events ◽  
Healthy Volunteers ◽  
Urinary Oxalate ◽  
Oxalate Decarboxylase ◽  
Clinical Trial Registry ◽  
Serious Adverse Events ◽  
Double Blind ◽  
Registration Number ◽  
Urinary Parameters

BackgroundHyperoxaluria is typically associated with excessive oxalate intake in the diet, decreased dietary calcium, hyperabsorption of oxalate, or increased endogenous production of oxalate. The disorder spectrum extends from recurrent kidney stones to ESKD. This clinical trial sought to evaluate the effectiveness of an acid stable oxalate decarboxylase (OxDC) to reduce urinary oxalate in healthy subjects on a high-oxalate diet.MethodsIn this prospective, double-blind, randomized, placebo-controlled, crossover clinical trial, 33 healthy volunteers were randomized into two crossover sequences separated by a 2-day washout period. A controlled high-oxalate diet (750–800 mg oxalate, 500–550 mg calcium daily) was utilized, and six 24-hour urine collections were measured. Subjects were given approximately 1000 U (micromoles per minute per milligram) of OxDC or placebo with meals three times daily during the 4 days of treatment.ResultsUrinary oxalate significantly decreased with OxDC treatment. The baseline corrected within-subject mean reduction in 24-hour urinary excretion (after OxDC dosing versus high-oxalate baseline preceding treatment) was 12.5 mg or 29% (P<0.001). OxDC treatment was effective (>5% reduction) in 31 of 33 subjects (94%). Compared with placebo, OxDC produced a 24% reduction (P<0.001) in 24-hour oxalate excretion. Other urinary parameters (creatinine, uric acid, citrate, magnesium, calcium) were not affected by OxDC. No serious adverse events and no product-related adverse events occurred.ConclusionsAn orally administered OxDC is capable of significantly reducing urinary oxalate levels in healthy volunteers on a high-oxalate diet without affecting creatinine clearance, urine creatinine, or other solutes related to supersaturation of calcium oxalate.Clinical Trial registry name and registration number:Evaluation of Nephure, and the Reduction of Dietary Oxalate, in Healthy Volunteers, NCT03661216

scholarly journals Analysis of serious adverse events in a paediatric fast breathing pneumonia clinical trial in Malawi

2019 ◽  
Vol 6 (1) ◽  
pp. e000415
Author(s):  
Evangelyn Nkwopara ◽  
Robert Schmicker ◽  
Tisungane Mvalo ◽  
Melda Phiri ◽  
Ajib Phiri ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Adverse Events ◽  
Study Drug ◽  
Serious Adverse Events ◽  
Double Blind ◽  
Additional Information ◽  
Link Type ◽  
Registration Number ◽  
Life Threatening ◽  
Randomised Controlled

IntroductionPneumonia is the leading infectious killer of children. We conducted a double-blind, randomised controlled non-inferiority trial comparing placebo to amoxicillin treatment for fast breathing pneumonia in HIV-negative children aged 2–59 months in Malawi. Occurrence of serious adverse events (SAEs) during the trial were examined to assess disease progression, co-morbidities, recurrence of pneumonia and side effects of amoxicillin.MethodsEnrolled children with fast breathing for age and a history of cough <14 days or difficult breathing were randomised to either placebo or amoxicillin for 3 days, and followed for 14 days to track clinical characteristics and outcomes. Medical history, physical exam, laboratory results and any chest radiographs collected at screening, enrolment and during hospitalisation were evaluated. All SAE reports were reviewed for additional information regarding hospitalisation, course of treatment and outcome.ResultsIn total, 102/1126 (9.0%) enrolled children with fast breathing pneumonia were reported to have a SAE. Seventy-five per cent (n=77) of SAEs were pneumonia-related (p<0.01). Children<2 years of age represented the greatest proportion (61/77, 79.2%) of those with a pneumonia-related SAE. In the amoxicillin group, there were 46 SAEs and 5 (10.9%) cases were identified as possibly related to study drug (4 gastroenteritis and 1 fever). There were no life-threatening pneumonia SAEs or deaths in either group, and by the time of exit from the study, all children recovered without sequelae.DiscussionIn this fast breathing pneumonia clinical trial, SAEs occurred infrequently in both the amoxicillin and placebo groups, and amoxicillin was well tolerated.Trial registration numberNCT02760420. https://clinicaltrials.gov/ct2/show/NCT02760420?term=ginsburg&rank=9.

Rituximab or Cyclophosphamide in the Treatment of Membranous Nephropathy: The RI-CYCLO Randomized Trial

2021 ◽  
Vol 32 (4) ◽  
pp. 972-982 ◽  
Author(s):  
Francesco Scolari ◽  
Elisa Delbarba ◽  
Domenico Santoro ◽  
Loreto Gesualdo ◽  
Antonello Pani ◽  
...  
Keyword(s):  
Complete Remission ◽  
Adverse Events ◽  
Membranous Nephropathy ◽  
Partial Remission ◽  
Pilot Trial ◽  
Clinical Trial Registry ◽  
Serious Adverse Events ◽  
First Line Therapy ◽  
Registration Number ◽  
Favorable Safety

BackgroundA cyclic corticosteroid-cyclophosphamide regimen is the first-line therapy for membranous nephropathy. Compared with this regimen, rituximab therapy might have a more favorable safety profile, but a head-to-head comparison is lacking.MethodsWe randomly assigned 74 adults with membranous nephropathy and proteinuria >3.5 g/d to rituximab (1 g) on days 1 and 15, or a 6-month cyclic regimen with corticosteroids alternated with cyclophosphamide every other month. The primary outcome was complete remission of proteinuria at 12 months. Other outcomes included determination of complete or partial remission at 24 months and occurrence of adverse events.ResultsAt 12 months, six of 37 patients (16%) randomized to rituximab and 12 of 37 patients (32%) randomized to the cyclic regimen experienced complete remission (odds ratio [OR], 0.4; 95% CI, 0.13 to 1.23); 23 of 37 (62%) receiving rituximab and 27 of 37 (73%) receiving the cyclic regimen had complete or partial remission (OR, 0.61; 95% CI, 0.23 to 1.63). At 24 months, the probabilities of complete and of complete or partial remission with rituximab were 0.42 (95% CI, 0.26 to 0.62) and 0.83 (95% CI, 0.65 to 0.95), respectively, and 0.43 (95% CI, 0.28 to 0.61) and 0.82 (95% CI, 0.68 to 0.93), respectively, with the cyclic regimen. Serious adverse events occurred in 19% of patients receiving rituximab and in 14% receiving the cyclic regimen.ConclusionsThis pilot trial found no signal of more benefit or less harm associated with rituximab versus a cyclic corticosteroid-cyclophosphamide regimen in the treatment of membranous nephropathy. A head-to-head, pragmatic comparison of the cyclic regimen versus rituximab may require a global noninferiority trial.Clinical Trial registry name and registration number:Rituximab versus Steroids and Cyclophosphamide in the Treatment of Idiopathic Membranous Nephropathy (RI-CYCLO),NCT03018535

scholarly journals Naoxuekang, Xinnaoshutong and Xuesaitong capsules for treating stroke: a protocol for a randomised controlled trial

BMJ Open ◽  
2017 ◽  
Vol 7 (11) ◽  
pp. e015983 ◽  
Author(s):  
Huiling Chen ◽  
Hongbo Cao ◽  
Xu Guo ◽  
Meidan Zhao ◽  
Qing Xia ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Facial Paralysis ◽  
Controlled Trial ◽  
Clinical Trial Registry ◽  
Double Blind ◽  
Initial Treatment Period ◽  
Double Blind Clinical Trial ◽  
Registration Number ◽  
Index Value ◽  
Randomised Controlled

IntroductionAfter stroke, hemiplegia, dysphasia and facial paralysis can manifest during the convalescent period. Currently, no Chinese patent medicine (CPM) is previously reported to cure each of these symptoms primarily, and thus, there are no relevant instructions for the use of CPM. This study presents a new approach based on comparative effectiveness research to distinguish the curative effects of three CPMs that are often used in stroke convalescence to determine the ideal medicine for the treatment of each symptom.Methods and analysisIn this multicentre and double-blind clinical trial, stratified randomisation is used to group the patients according to their primary symptoms (hemiplegia, dysphasia and facial paralysis). Three strata will be enrolled, with 80 eligible participants included in each stratum. Each stratum will be randomly and equally divided into four groups, and each group will receive one of the following treatments: Naoxuekang, Xinnaoshutong (XNST), Xuesaitong (XST) or placebo. This study will include two stages: the initial treatment period (30 days) and a follow-up period (180 days). Three replicates for each data point will be completed during this trial. The first visit will occur on day 0 after enrolment, the second visit on day 30±2 and the third visit on day 210±5. The Delphi technique is adopted to achieve index weighting, which ensures that the evaluation outcome is patient oriented. The weighted index value will be computed as the final measurement index of the outcome.Ethics and disseminationThis study has been approved by the Medical Ethics Committee of Tianjin University of Traditional Chinese Medicine (registration number TJUTCM-EC20160007). The results will be offered for publication in peer-reviewed journals.Trial registration numberThis trial was registered with the Chinese Clinical Trial Registry (ChiCTR-IOR-17010397). The date of registration was 11 January 2017.

scholarly journals Safety of Liraglutide in Type 2 Diabetes and Chronic Kidney Disease

2020 ◽  
Vol 15 (4) ◽  
pp. 465-473 ◽  
Author(s):  
Johannes F.E. Mann ◽  
Vivian A. Fonseca ◽  
Neil R. Poulter ◽  
Itamar Raz ◽  
Thomas Idorn ◽  
...  
Keyword(s):  
Adverse Events ◽  
Cox Regression ◽  
Severe Hypoglycemia ◽  
Standard Of Care ◽  
Clinical Trial Registry ◽  
Serious Adverse Events ◽  
Link Type ◽  
Urine Albumin ◽  
Registration Number ◽  
Glucagon Like Peptide 1

Background and objectivesThe glucagon-like peptide-1 receptor agonist liraglutide demonstrated cardiovascular and kidney benefits in the LEADER trial, particularly in participants with CKD.Design, setting, participants, & measurementsThis post hoc analysis evaluated the safety of liraglutide treatment in patients with CKD in LEADER. Overall, 9340 patients were randomized to liraglutide or placebo, both in addition to standard of care. Of those, 2158 patients had CKD versus 7182 without CKD (defined as eGFR <60 versus ≥60 ml/min per 1.73 m2, respectively); 966 patients had macroalbuminuria and 2456 had microalbuminuria (urine albumin-creatinine ratio >300 mg/g and ≥30 to ≤300 mg/g, respectively). At baseline, the mean eGFR in patients with CKD was 46±11 ml/min per 1.73 m2 versus 91±22 ml/min per 1.73 m2 in those without CKD. Time to first event within event groups was analyzed using Cox regression with treatment group, baseline eGFR group, or baseline albuminuria group as fixed factors.ResultsOverall, serious adverse events were more frequently recorded in patients with CKD compared with those without CKD (59% versus 50%; interaction P=0.11); however, they occurred to the same extent in those on liraglutide versus placebo. Similarly, no interaction of adverse events with randomized therapy was observed in patients with micro- or macro- versus normoalbuminuria (interaction P=0.11). Risk of severe hypoglycemia was significantly reduced with liraglutide versus placebo in patients with CKD or with micro- or macroalbuminuria (hazard ratio, 0.63 [95% CI, 0.43 to 0.91] and 0.57 [95% CI, 0.40 to 0.82], respectively).ConclusionsIn LEADER, the use of liraglutide in those with CKD was safe, with no difference between patients with and without CKD.Clinical Trial registry name and registration numberClinicalTrials.gov; NCT01179048 (https://clinicaltrials.gov/ct2/show/NCT01179048).

Randomised controlled trial of escitalopram for cervical dystonia with dystonic jerks/tremor

2018 ◽  
Vol 89 (6) ◽  
pp. 579-585 ◽  
Author(s):  
Evelien Zoons ◽  
Jan Booij ◽  
Catherine C S Delnooz ◽  
Joke M Dijk ◽  
Yasmine E M Dreissen ◽  
...  
Keyword(s):  
Adverse Events ◽  
Cervical Dystonia ◽  
Rating Scales ◽  
Psychiatric Symptoms ◽  
Controlled Trial ◽  
Serious Adverse Events ◽  
Double Blind ◽  
Registration Number ◽  
Randomised Controlled

ObjectiveTrials for additional or alternative treatments for cervical dystonia (CD) are scarce since the introduction of botulinum neurotoxin (BoNT). We performed the first trial to investigate whether dystonic jerks/tremor in patients with CD respond to the selective serotonin reuptake inhibitor (SSRI) escitalopram.MethodsIn a randomised, double-blind, crossover trial, patients with CD received escitalopram and placebo for 6 weeks. Treatment with BoNT was continued, and scores on rating scales regarding dystonia, psychiatric symptoms and quality of life (QoL) were compared. Primary endpoint was the proportion of patients that improved at least one point on the Clinical Global Impression Scale for jerks/tremor scored by independent physicians with experience in movement disorders.ResultsFifty-threepatients were included. In the escitalopram period, 14/49 patients (29%) improved on severity of jerks/tremor versus 11/48 patients (23%) in the placebo period (P=0.77). There were no significant differences between baseline and after treatment with escitalopram or placebo on severity of dystonia or jerks/tremor. Psychiatric symptoms and QoL improved significantly in both periods compared with baseline. There were no significant differences between treatment with escitalopram and placebo for dystonia, psychiatric or QoL rating scales. During treatment with escitalopram, patients experienced slightly more adverse events, but no serious adverse events occurred.ConclusionIn this innovative trial, no add-on effect of escitalopram for treatment of CD with jerks was found on motor or psychiatric symptoms. However, we also did not find a reason to withhold patients treatment with SSRIs for depression and anxiety, which are common in dystonia.Trial registration numberNTR2178.

scholarly journals Efficacy and Safety of Remdesivir for COVID-19 Treatment: An Analysis of Randomized, Double-Blind, Placebo-Controlled Trials

2020 ◽  
Author(s):  
Yun Zhu ◽  
Zhaowei Teng ◽  
Lirong Yang ◽  
Shuanglan Xu ◽  
Jie Liu ◽  
...  
Keyword(s):  
Adverse Events ◽  
Discharge Rate ◽  
Meta Analysis ◽  
Controlled Trials ◽  
Cochrane Central Register ◽  
Serious Adverse Events ◽  
Double Blind ◽  
Randomized Controlled ◽  
Central Register ◽  
Registration Number

AbstractBACKGROUNDRemdesivir, an inhibitor of viral RNA-dependent RNA polymerases, has been identified as a candidate for COVID-19 treatment. However, the therapeutic effect of remdesivir is controversial.METHODSWe searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials, from inception to June 11, 2020 for randomized controlled trials on the clinical efficacy of remdesivir. The main outcomes were discharge rate, mortality, and adverse events. This study is registered at INPLASY (INPLASY202060046).RESULTSData of 1075 subjects showed that remdesivir significantly increased the discharge rate of patients with COVID-19 compared with the placebo (50.4% vs. 45.29%; relative risk [RR] 1.19 [95% confidence interval [CI], 1.05–1.34], I2 = 0.0%, P = 0.754). It also significantly decreased mortality (8.18% vs. 12.70%; RR 0.64 [95% CI, 0.44–0.92], I2 = 45.7%, P = 0.175) compared to the placebo. Data of 1296 subjects showed that remdesivir significantly decreased the occurrence of serious adverse events (RR 0.77 [95% CI, 0.63–0.94], I2 = 0.0%, P = 0.716).CONCLUSIONRemdesivir is efficacious and safe for the treatment of COVID-19.TRIAL REGISTRATION NUMBERThis study is registered at the International Platform of Registered Systematic Review and Meta-analysis Protocols (INPLASY202060046).

scholarly journals 1288. Phase 1 First-in-Human Single- and Multiple-Ascending Dose Trial Demonstrates Pharmacokinetics (PK) and Tolerability of SPR720, an Oral DNA GyrB Inhibitor for Mycobacterial Infections

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S659-S659
Author(s):  
Angela Talley ◽  
Archie Thurston ◽  
Grayson Moore ◽  
Myriah M Satterfield ◽  
Erika L Manyak ◽  
...  
Keyword(s):  
Adverse Events ◽  
Healthy Volunteers ◽  
Controlled Trial ◽  
Phase 1 ◽  
Safety Data ◽  
Elderly Subjects ◽  
Independent Contractor ◽  
Serious Adverse Events ◽  
Healthy Elderly ◽  
Dose Proportional

Abstract Background SPR720 (phosphate pro-drug of SPR719) is a novel aminobenzimidazole bacterial DNA gyrase (GyrB) inhibitor in development for non-tuberculous mycobacterial lung disease (NTM-LD) and pulmonary tuberculosis. SPR719 has broad-spectrum activity versus clinically relevant mycobacteria in vitro and in murine and hollow fiber (HF) infection models. In this first-in-human single ascending dose (SAD) /multiple ascending dose (MAD) study, the safety, tolerability and pharmacokinetics (PK) of SPR720/SPR719 were evaluated in healthy volunteers. Methods This was a Phase 1 randomized, double-blind, placebo-controlled trial with 7 SAD cohorts (including a food effect cohort) and 5 MAD cohorts. Healthy volunteers (n=8/cohort, 3:1 randomization) received SPR720 or placebo in single oral doses of ranging from 100 mg to 2000 mg or repeat total daily doses ranging from 500 mg to 1500 mg for 7 or 14 days. Safety monitoring and PK sampling occurred throughout the trial. Plasma and urine concentrations of SPR720/SPR719 were measured by validated LC-MS/MS methods. PK parameters were calculated using non-compartmental analysis. Results A total of 96 subjects (including 8 healthy elderly subjects, age ≥ 65 years) were randomized and received study drug. SPR720 was well-tolerated at daily doses up to 1000 mg for up to 14 days. Across SAD/MAD cohorts, the most common adverse events were gastrointestinal (nausea, vomiting and diarrhea) and headache, all of mild or moderate severity and dose dependent. No serious adverse events were reported. Across SAD cohorts, a dose proportional and greater-than-dose proportional increase in SPR719 plasma Cmax and AUC0-24, respectively were observed. SPR720 was rapidly absorbed with a mean SPR719 t1/2 of 2.9-4.5 h. Dosing with food decreased SPR719 plasma AUC by ~20%. No clinically meaningful effect of age on plasma AUC was observed. In the MAD cohorts, SPR719 plasma exposure declined approximately 40% between Day 1 and Day 7, suggesting induction of an elimination pathway. However, plasma AUC0-24 was similar at Days 7 and 14. Conclusion Together with HF pharmacodynamic data, human PK and safety data for SPR720 suggest that predicted therapeutic exposures can be attained with a well-tolerated once-daily dose. Further evaluation in a Phase 2 NTM-LD trial is planned. Disclosures Angela Talley, MD, Spero Therapeutics (Employee, Shareholder) Archie Thurston, Jr., PhD, Spero Therapeutics (Consultant) Grayson Moore, BA, RN, Spero Therapeutics, Inc. (Shareholder, Independent Contractor) Vipul Kumar, PhD, Spero Therapeutics (Employee, Shareholder) Suzanne Stokes, PhD, Spero Therapeutics (Employee, Shareholder) Aaron Dane, MSc, Spero theraputics (Consultant) David Melnick, MD, Spero Therapeutics (Employee)Spero Therapeutics (Employee)

Tonabersat, a Gap-Junction Modulator: Efficacy and Safety in Two Randomized, Placebo-Controlled, Dose-Ranging Studies of Acute Migraineceph

Cephalalgia ◽  
2009 ◽  
Vol 29 (2_suppl) ◽  
pp. 17-27 ◽  
Author(s):  
SD Silberstein ◽  
J Schoenen ◽  
H Göbel ◽  
HC Diener ◽  
AH Elkind ◽  
...  
Keyword(s):  
Adverse Events ◽  
North American ◽  
Cortical Spreading Depression ◽  
Spreading Depression ◽  
Plasma Concentrations ◽  
International Study ◽  
Maximum Plasma ◽  
Serious Adverse Events ◽  
Double Blind ◽  
Dose Ranging

Tonabersat is a novel benzopyran derivative that blocks the cortical spreading depression proposed to be associated with migraine attacks. The ability of single oral doses of 15, 25, 40 and 80 mg of tonabersat to relieve the symptoms of moderate to severe migraine was evaluated in 859 migraineurs enrolled in two dose-ranging, double-blind, randomized, placebo-controlled, parallel-group trials, one international and the other North American. In the international study, significantly more patients given tonabersat than given placebo experienced relief of headache pain at 2 h (15 mg, 36.8%; 40 mg, 40.7%), the principal efficacy variable, and at 4 h (40 mg, 63.0%) and complete abolition of headache at 4 h (40 mg, 34.3%). None of the primary or secondary efficacy variables indicated significant differences between tonabersat and placebo in the North American study. Tonabersat was generally well tolerated, with dizziness and nausea the most common side-effects. Serious adverse events were uncommon, and no patient withdrew from either study because of adverse events. These results suggest a possible interplay between tonabersat pharmacokinetics (the relatively long time required to reach maximum plasma concentrations) and patient characteristics (previous triptan exposure) in the management of acute migraine attacks. Based on the pharmacokinetics and actions on cortical spreading depression, tonabersat may have potential value in migraine prophylaxis.

Adverse events and blinding in two randomized trials of hyperbaric oxygen for persistent post-concussive symptoms

2019 ◽  
pp. 331-340
Author(s):  
Susan Churchill ◽  
◽  
Kayla Deru ◽  
Lindell K. Weaver ◽  
Steffanie H. Wilson ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Adverse Events ◽  
Hyperbaric Oxygen ◽  
Gas Flow ◽  
Randomized Trials ◽  
Symptom Improvement ◽  
Sham Control ◽  
Serious Adverse Events ◽  
Double Blind ◽  
To Receive

Safety monitoring and successful blinding are important features of randomized, blinded clinical trials. We report chamber- and protocol-related adverse events (AEs) for participants enrolled in two randomized, double-blind clinical trials of hyperbaric oxygen (HBO2) for persistent post-concussive symptoms clinicaltrials.gov identifiers NCT01306968, HOPPS, and NCT01611194, BIMA), as well as the success of maintaining the blind with a low-pressure sham control arm. In both studies, participants were randomized to receive HBO2 (1.5 atmospheres absolute, >99% oxygen) or sham chamber sessions (1.2 atmospheres absolute, room air). In 143 participants undergoing 4,245 chamber sessions, chamber-related adverse events were rare (1.1% in the HOPPS study, 2.2% in the BIMA study). Minor, non-limiting barotrauma was the most frequently reported. Rarely, some participants experienced headache with chamber sessions. No serious adverse events were associated with chamber sessions. An allocation questionnaire completed after intervention revealed that the sham control arm adequately protected the blind in both trials. Participants based allocation assumptions on symptom improvement or lack of symptom improvement and could not discern intervention arm by pressure, smell, taste, or gas flow.

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