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Shortening antibiotic duration in the treatment of acute cholangitis: rationale and study protocol for an open-label randomized controlled trial.

ABSTRACT: BACKGROUND:Antimicrobial therapy with appropriate biliary drainage is considered the standard of care for acute cholangitis, but the optimal duration of antimicrobial therapy remains unknown. Seven to 10?days of antimicrobial therapy are common for the treatment of acute cholangitis, but a recent retrospective cohort study suggested a shorter duration might be effective. A shorter duration of antimicrobial therapy can be beneficial in decreasing the length of hospital stay, improving patients' quality of life, decreasing adverse effects, and even contributing to a decrease in the occurrence of antimicrobial resistance. METHODS/DESIGN:We will conduct a multi-centre, open-label, randomized, non-inferiority trial to compare short-course therapy (SCT) with conventional long-course therapy (LCT) in treating patients with acute cholangitis. SCT consists of 5-day intravenous antimicrobial therapy if the patients had clinical improvement, while at least 7?days of intravenous antibiotics will be provided to the LCT group. The primary outcome is clinical cure at 30?days after onset. Patients will be randomly assigned in an open-label fashion. A total sample size of 150 was estimated to provide a power of 80% with a one-sided ? level of 2.5% and a non-inferiority margin of 10%. DISCUSSION:This trial is expected to reveal whether SCT is non-inferior to conventional LCT or not, and may provide evidence that one can shorten the treatment duration for acute cholangitis for the benefit of patients. TRIAL REGISTRATION:University Hospital Medical Information Network, UMIN000028382. Registered on 30 August 2017.

SUBMITTER: Iwata K

PROVIDER: S-EPMC6969404 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Shortening antibiotic duration in the treatment of acute cholangitis: rationale and study protocol for an open-label randomized controlled trial.

Iwata Kentaro K Doi Asako A Oba Yuichiro Y Matsuo Hiroo H Ebisawa Kei K Nagata Manabu M Nishimura Sho S Yoshimura Kenichi K Masuda Atsuhiro A Shiomi Hideyuki H Kodama Yuzo Y

Trials 20200117 1

<h4>Background</h4>Antimicrobial therapy with appropriate biliary drainage is considered the standard of care for acute cholangitis, but the optimal duration of antimicrobial therapy remains unknown. Seven to 10 days of antimicrobial therapy are common for the treatment of acute cholangitis, but a recent retrospective cohort study suggested a shorter duration might be effective. A shorter duration of antimicrobial therapy can be beneficial in decreasing the length of hospital stay, improving pat ...[more]

PMID: 31952554

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Project description:IntroductionA major knowledge gap in the treatment of complicated Staphylococcus aureus bacteraemia (SAB) is the optimal duration of antibiotic therapy. Safe shortening of antibiotic therapy has the potential to reduce adverse drug events, length of hospital stay and costs. The objective of the SAFE trial is to evaluate whether 4 weeks of antibiotic therapy is non-inferior to 6 weeks in patients with complicated SAB.Methods and analysisThe SAFE-trial is a multicentre, non-inferiority, open-label, parallel group, randomised controlled trial evaluating 4 versus 6 weeks of antibiotic therapy for complicated SAB. The study is performed in 15 university hospitals and general hospitals in the Netherlands. Eligible patients are adults with methicillin-susceptible SAB with evidence of deep-seated or metastatic infection and/or predictors of complicated SAB. Only patients with a satisfactory clinical response to initial antibiotic treatment are included. Patients with infected prosthetic material or an undrained abscess of 5 cm or more at day 14 of adequate antibiotic treatment are excluded. Primary outcome is success of therapy after 180 days, a combined endpoint of survival without evidence of microbiologically confirmed disease relapse. Assuming a primary endpoint occurrence of 90% in the 6 weeks group, a non-inferiority margin of 7.5% is used. Enrolment of 396 patients in total is required to demonstrate non-inferiority of shorter antibiotic therapy with a power of 80%. Currently, 152 patients are enrolled in the study.Ethics and disseminationThis is the first randomised controlled trial evaluating duration of antibiotic therapy for complicated SAB. Non-inferiority of 4 weeks of treatment would allow shortening of treatment duration in selected patients with complicated SAB. This study is approved by the Medical Ethics Committee VUmc (Amsterdam, the Netherlands) and registered under NL8347 (the Netherlands Trial Register). Results of the study will be published in a peer-reviewed journal.Trial registration numberNL8347 (the Netherlands Trial Register).

Project description:Introduction: Open-label placebos have been proposed as way of using long recognized analgesic placebo effects in an ethical manner. Recent evidence shows efficacy of open-label placebos for clinical conditions, but there is need for more research on open-label placebos in acute pain. In the treatment of acute postoperative pain, minimization of opioid related side effects remains one of the key challenges. Therefore, this study aims at investigating the potential of adding unconditioned open-label placebos to treatment as usual as a means of reducing opioid consumption and its related side effects in patients with acute postoperative pain. Methods and Analysis: This is the protocol of an ongoing single site randomized controlled trial. The first patient was enrolled in May 2020. In total, 70 patients suffering from acute postoperative pain following dorsal lumbar interbody fusion are randomized to either a treatment as usual group or an experimental intervention group. The treatment as usual group consists of participants receiving a patient-controlled morphine pump. On day 1 and 2 post-surgery, patients in the intervention group receive, in addition to treatment as usual, two open-label placebo injections per day along with an evidence-based treatment rationale explaining the mechanisms of placebos. The primary outcome is measured by means of self-administered morphine during day 1 and 2 post-surgery. Several other outcome measures including pain intensity and adverse events as well as potential predictors of placebo response are assessed. Analysis of covariance will be used to answer the primary research question and additional statistical techniques such as generalized linear mixed models will be applied to model the temporal course of morphine consumption. Discussion: This study will provide valuable insights into the efficacy of open-label placebos in acute pain and will potentially constitute an important step toward the implementation of open-label placebos in the clinical management of acute postoperative pain. In addition, it will shed light on a cost-efficient and patient-centered strategy to reduce opioid consumption and its related side effects, without any loss in pain management efficacy. Ethics and Dissemination: The "Ethikkommission Nordwest- und Zentralschweiz" (BASEC2020-00099) approved the study protocol. Results of the analysis will be submitted for publication in a peer-reviewed journal. Clinical Trial Registration: The study is registered at ClinicalTrials.gov (NCT04339023) and is listed in the Swiss national registry at kofam.ch (SNCTP000003720).

Project description:BackgroundChronic active antibody-mediated rejection (caAMR) in kidney transplants is associated with irreversible tissue damage and a leading cause of graft loss in the long-term. However, the treatment for caAMR remains a challenge to date. Recently, tocilizumab, a recombinant humanized monoclonal antibody directed against the human interleukin-6 (IL-6) receptor, has shown promise in the treatment of caAMR. However, it has not been systematically investigated so far underscoring the need for randomized controlled studies in this area.MethodsThe INTERCEPT study is an investigator-driven randomized controlled open-label multi-center trial in kidney transplant recipients to assess the efficacy of tocilizumab in the treatment of biopsy-proven caAMR. A total of 50 recipients with biopsy-proven caAMR at least 12 months after transplantation will be randomized to receive either tocilizumab (n = 25) added to our standard of care (SOC) maintenance treatment or SOC alone (n = 25) for a period of 24 months. Patients will be followed for an additional 12 months after cessation of study medication. After the inclusion biopsies at baseline, protocol kidney graft biopsies will be performed at 12 and 24 months. The sample size calculation assumed a difference of 5 ml/year in slope of estimated glomerular filtration rate (eGFR) between the two groups for 80% power at an alpha of 0.05. The primary endpoint is the slope of eGFR at 24 months after start of treatment. The secondary endpoints include assessment of the following at 12, 24, and 36 months: composite risk score iBox, safety, evolution and characteristics of donor-specific antibodies (DSA), graft histology, proteinuria, kidney function assessed by measured GFR (mGFR), patient- and death-censored graft survival, and patient-reported outcomes that include transplant-specific well-being, adherence to immunosuppressive medications and perceived threat of the risk of graft rejection.DiscussionNo effective treatment exists for caAMR at present. Based on the hypothesis that inhibition of IL-6 receptor by tocilizumab will reduce antibody production and reduce antibody-mediated damage, our randomized trial has a potential to provide evidence for a novel treatment strategy for caAMR, therewith slowing the decline in graft function in the long-term.Trial registrationClinicalTrials.gov NCT04561986. Registered on September 24, 2020.

Project description:Background and purposeRecombinant human TNK tissue-type plasminogen activator (rhTNK-tPA) was not inferior to alteplase for ischaemic stroke within 4.5 hours. Our study aimed to investigate the efficacy and safety of rhTNK-tPA in patients who had an ischaemic stroke due to large vessel occlusion (LVO) of anterior circulation beyond 4.5 hours.Methods and designTenecteplase Reperfusion Therapy in Acute Ischaemic Cerebrovascular Events-III (TRACE III) is a multicentre, prospective, randomised, open-label, blind endpoint, controlled clinical trial. Patients who had an ischaemic stroke due to anterior circulation LVO (internal carotid artery, middle cerebral artery M1 and M2 segments) within 4.5-24 hours from last known well (including wake-up stroke and no witness stroke) and with salvageable tissue (ischaemic core volume <70 mL, mismatch ratio ≥1.8 and mismatch volume ≥15 mL) based on CT perfusion or MRI perfusion-weighted imaging (PWI) were included and randomised to rhTNK-tPA 0.25 mg/kg (single bolus) to a maximum of 25 mg or standard medical therapy. Specially, we will exclude patients who are intended for direct thrombectomy. All will be followed up for 90 days.Study outcomesPrimary efficacy outcome is modified Rankin Scale (mRS) score ≤1 at 90 days. Secondary efficacy outcomes include ordinal distribution of mRS at 90 days, major neurological improvement defined by a decrease ≥8 points compared with the initial deficit or a score ≤1 on the National Institutes of Health Stroke Scale (NIHSS) at 72 hours, mRS score ≤2 at 90 days, the rate of improvement on Tmax >6 s at 24 hours and NIHSS score change from baseline at 7 days. Safety outcomes are symptomatic intracerebral haemorrhage within 36 hours and mortality at 90 days.DiscussionTRACE III will provide evidence for the efficacy and safety of rhTNK-tPA in patients who had an ischaemic strokes due to anterior circulation LVO beyond 4.5 hours.Trial registration numberNCT05141305.

Project description:BackgroundAcute otitis media (AOM) is an acute inflammation of the middle ear commonly found in children, for which antibiotics are frequently prescribed. However, antibiotics are beneficial for only one third of AOM cases, and then, with only modest benefit. Since antibiotic use leads to risk of side effects and resistance, effective alternative treatments are required. Corticosteroids are a candidate because of their anti-inflammatory effects, although evidence of their efficacy and harms is insufficient. Accordingly, we plan a large, rigorous clinical trial to test this. Initially, we will test pre-specified methods and procedures (including the overall process, resources, management, and scientific components) in a pilot study of corticosteroids for AOM, which will inform a future, definitive trial.MethodsThis is a pilot pragmatic, randomised, open-label, single-blind, controlled study of corticosteroids as either monotherapy or an addition to antibiotics in 60 children aged 6 months to 12 years with AOM in two cities (Jakarta and Bekasi) in Indonesia. We will randomise eligible children to prednisolone or control. We will also stratify by disease severity and randomise those with mild AOM to expectant observation plus prednisolone or observation alone and those with severe AOM to prednisolone plus antibiotic or antibiotic alone. Our outcomes are to determine (1) recruitment rates, (2) the success of the study procedures, (3) the ability to measure planned outcomes of the proposed main study, (4) the compliance to study visits and study medication, and (5) verification of the sample size calculation for the main study. We will also assess middle ear effusion using tympanometry as part of a mechanistic sub-study.DiscussionThis study will test all procedures in preparation for the main study, including several potential obstacles and challenges from the perspective of participating physicians, nurses, pharmacists, and the parents of eligible children. This information will be useful for developing strategies to overcome practical and procedural issues. This study may also provide information about the effects of corticosteroids on middle ear effusion in AOM.Trial registrationStudy registry number: ACTRN12618000049279. Name of registry: the Australian New Zealand Clinical Trials Registry (ANZCTR). Date of registration: 16 January 2018.

Project description:Both hyperglycaemia and hypoglycaemia in acute ischaemic stroke (AIS) are associated with increased infarct size and worse functional outcomes. Thus, therapies that can maintain normoglycaemia during stroke are clinically important. Glucagon-like peptide 1 (GLP-1) analogues, including exenatide, are routinely used in the treatment of hyperglycaemia in type 2 diabetes, but data on the usefulness of this class of agents in the management of elevated glucose levels in AIS are limited. Owing to their glucose-dependent mechanism of action, GLP-1 analogues are associated with a low risk of hypoglycaemia, which may give them an advantage over intensive insulin therapy in the acute management of hyperglycaemia in this setting.The Short-Term EXenatide therapy in Acute ischaemic Stroke study is a randomised, open-label, parallel-group pilot study designed to investigate the efficacy of exenatide at lowering blood glucose levels in patients with hyperglycaemia with AIS. A total of 30 patients presenting with AIS and blood glucose levels >10 mmol/L will be randomised to receive the standard therapy (intravenous insulin) or intravenous exenatide for up to 72 h. Outcomes including blood glucose levels within the target range (5-10 mmol/L), the incidence of hypoglycaemia and the feasibility of administering intravenous exenatide in this patient population will be assessed. A follow-up visit at 3 months will facilitate evaluation of neurological outcomes post-stroke.This study has been approved by the local Institutional Review Board (Northern Sydney Local Health District Human Research Ethics Committee). The study results will be communicated via presentations at scientific conferences and through publication in peer-reviewed journals.As GLP-1 analogues require elevated glucose levels to exert their insulin potentiating activity, the use of exenatide in the management of hyperglycaemia in AIS may reduce the incidence of hypoglycaemia, thereby conferring a benefit in morbidity and mortality for patients in the long term.ACTRN12614001189617.

Dataset Information

Shortening antibiotic duration in the treatment of acute cholangitis: rationale and study protocol for an open-label randomized controlled trial.

Publications

Shortening antibiotic duration in the treatment of acute cholangitis: rationale and study protocol for an open-label randomized controlled trial.

Similar Datasets

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