scholarly journals Shortening Antibiotic Duration in the Treatment of Acute Cholangitis. Rationale and Study Protocol for an Open Label Randomized Controlled Trial.

2019 ◽  
Author(s):  
Kentaro Iwata ◽  
Asako Doi ◽  
Yuichiro Oba ◽  
Hiroo Matsuo ◽  
Kei Ebisawa ◽  
...  
Keyword(s):  
Antimicrobial Therapy ◽  
Controlled Trial ◽  
Acute Cholangitis ◽  
Length Of Hospital Stay ◽  
Standard Of Care ◽  
Total Sample ◽  
Open Label ◽  
Short Course ◽  
Antibiotic Duration ◽  
Long Course

Abstract Background: Antimicrobial therapy with appropriate biliary drainage is considered the standard of care of acute cholangitis, but the optimal duration of antimicrobial therapy remains unknown. Seven to 10 days of antimicrobial therapy is common for the treatment of acute cholangitis, but recent retrospective cohort study suggested shorter duration might be effective enough. 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 decrease in the occurrence of antimicrobial resistance. Methods/design: We will conduct a multi-center, 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 LCT group. The primary outcome is clinical cure at 30 days after their onset. Patients will be randomly assigned with open label fashion. A total sample size of 150 was estimated to provide a power of 80% with a one-sided alpha 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 able to shorten the treatment duration for acute cholangitis for the benefit of the patients.

scholarly journals Shortening Antibiotic Duration in the Treatment of Acute Cholangitis. Rationale and Study Protocol for an Open Label Randomized Controlled Trial.

2019 ◽  
Author(s):  
Kentaro Iwata ◽  
Asako Doi ◽  
Yuichiro Oba ◽  
Hiroo Matsuo ◽  
Kei Ebisawa ◽  
...  
Keyword(s):  
Antimicrobial Therapy ◽  
Controlled Trial ◽  
Acute Cholangitis ◽  
Length Of Hospital Stay ◽  
Standard Of Care ◽  
Total Sample ◽  
Open Label ◽  
Short Course ◽  
Antibiotic Duration ◽  
Long Course

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 is 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-center, 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 alpha 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.

scholarly journals GLUCOCOVID: A controlled trial of methylprednisolone in adults hospitalized with COVID-19 pneumonia

2020 ◽  
Author(s):  
Luis Corral-Gudino ◽  
Alberto Bahamonde ◽  
Francisco Arnaiz-Revillas ◽  
Julia Gómez-Barquero ◽  
Jesica Abadía-Otero ◽  
...  
Keyword(s):  
Controlled Trial ◽  
Composite Endpoint ◽  
Standard Of Care ◽  
Control Group ◽  
Open Label ◽  
Protein Levels ◽  
Intention To Treat ◽  
Reactive Protein ◽  
Short Course ◽  
Stratified Analysis

ABSTRACTBackgroundWe aimed to determine whether a 6-day course of intravenous methylprednisolone (MP) improves outcome in patients with SARS CoV-2 infection at risk of developing Acute Respiratory Distress Syndrome (ARDS).MethodsMulticentric, partially randomized, preference, open-label trial, including adults with COVID-19 pneumonia, impaired gas exchange and biochemical evidence of hyper-inflammation. Patients were assigned to standard of care (SOC), or SOC plus intravenous MP [40mg/12h 3 days, then 20mg/12h 3 days]. The primary endpoint was a composite of death, admission to the intensive care unit (ICU) or requirement of non-invasive ventilation (NIV).ResultsWe analyzed 85 patients (34, randomized to MP; 22, assigned to MP by clinician’s preference; 29, control group). Patients’ age (mean 68±12 yr) was related to outcome. The use of MP was associated with a reduced risk of the composite endpoint in the intention-to-treat, age-stratified analysis (combined risk ratio -RR-0.55 [95% CI 0.33-0.91]; p=0.024). In the per-protocol analysis, RR was 0.11 (0.01-0.83) in patients aged 72 yr or less, 0.61 (0.32-1.17) in those over 72 yr, and 0.37 (0.19-0.74, p=0.0037) in the whole group after age-adjustment by stratification. The decrease in C-reactive protein levels was more pronounced in the MP group (p=0.0003). Hyperglycemia was more frequent in the MP group.ConclusionsA short course of MP had a beneficial effect on the clinical outcome of severe COVID-19 pneumonia, decreasing the risk of the composite end point of admission to ICU, NIV or death.

scholarly journals Randomized controlled trial of convalescent plasma therapy against standard therapy in patients with severe COVID-19 disease

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Manaf AlQahtani ◽  
Abdulkarim Abdulrahman ◽  
Abdulrahman Almadani ◽  
Salman Yousif Alali ◽  
Alaa Mahmood Al Zamrooni ◽  
...  
Keyword(s):  
Standard Therapy ◽  
Primary Outcome ◽  
Controlled Trial ◽  
Severe Disease ◽  
Pilot Trial ◽  
Standard Of Care ◽  
Primary Outcome Measure ◽  
Secondary Outcome ◽  
Open Label ◽  
Plasma Therapy

AbstractConvalescent plasma (CP) therapy in COVID-19 disease may improve clinical outcome in severe disease. This pilot study was undertaken to inform feasibility and safety of further definitive studies. This was a prospective, interventional and randomized open label pilot trial in patients with severe COVID-19. Twenty COVID-19 patients received two 200 ml transfusions of convalescent patient CP over 24-h compared with 20 who received standard of care. The primary outcome was the requirement for ventilation (non-invasive or mechanical ventilation). The secondary outcomes were biochemical parameters and mortality at 28 days. The CP group were a higher risk group with higher ferritin levels (p < 0.05) though respiratory indices did not differ. The primary outcome measure was required in 6 controls and 4 patients on CP (risk ratio 0.67, 95% CI 0.22–2.0, p = 0.72); mean time on ventilation (NIV or MV) did not differ. There were no differences in secondary measures at the end of the study. Two patients died in the control and one patient in the CP arm. There were no significant differences in the primary or secondary outcome measures between CP and standard therapy, although a larger definitive study is needed for confirmation. However, the study did show that CP therapy appears to be safe in hospitalized COVID-19 patients with hypoxia.Clinical trials registration NCT04356534: 22/04/2020.

scholarly journals COVIDENZA - A prospective, multicenter, randomized PHASE II clinical trial of enzalutamide treatment to decrease the morbidity in patients with Corona virus disease 2019 (COVID-19): a structured summary of a study protocol for a randomised controlled trial

Trials ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Karin Welén ◽  
Anna K Överby ◽  
Clas Ahlm ◽  
Eva Freyhult ◽  
David Robinsson ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Virus Disease ◽  
Controlled Trial ◽  
Scale Up ◽  
Standard Of Care ◽  
University Hospital ◽  
Ordinal Scale ◽  
Open Label ◽  
Full Protocol ◽  
Exploration Phase

Abstract Objectives The main goal of the COVIDENZA trial is to evaluate if inhibition of testosterone signalling by enzalutamide can improve the outcome of patients hospitalised for COVID-19. The hypothesis is based on the observation that the majority of patients in need of intensive care are male, and the connection between androgen receptor signalling and expression of TMPRSS2, an enzyme important for SARS-CoV-2 host cell internalization. Trial design Hospitalised COVID-19 patients will be randomised (2:1) to enzalutamide plus standard of care vs. standard of care designed to identify superiority. Participants Included participants, men or women above 50 years of age, must be hospitalised for PCR confirmed COVID-19 symptoms and not in need of immediate mechanical ventilation. Major exclusion criteria are breast-feeding or pregnant women, hormonal treatment for prostate or breast cancer, treatment with immunosuppressive drugs, current symptomatic unstable cardiovascular disease (see Additional file 1 for further details). The trial is registered at Umeå University Hospital, Region Västerbotten, Sweden and 8 hospitals are approved for inclusion in Sweden. Intervention and comparator Patients randomised to the treatment arm will be treated orally with 160 mg (4x40 mg) enzalutamide (Xtandi®) daily, for five consecutive days. The study is not placebo controlled. The comparator is standard of care treatment for patients hospitalised with COVID-19. Main outcomes The primary endpoints of the study are (time to) need of mechanical ventilation or discharge from hospital as assessed by a clinical 7-point ordinal scale (up to 30 days after inclusion). Randomisation Randomisation was stratified by center and sex. Each strata was randomized separately with block size six with a 2:1 allocation ratio (enzalutamide + “standard of care”: “standard of care”). The randomisation list, with consecutive subject numbers, was generated by an independent statistician using the PROC PLAN procedure of SAS version 9.4 software (SAS Institute, Inc, Cary, North Carolina) Blinding (masking) This is an open-label trial. Numbers to be randomised (sample size) The trial is designed to have three phases. The first, an exploration phase of 45 participants (30 treatment and 15 control) will focus on safety and includes a more extensive laboratory assessment as well as more frequent safety evaluation. The second prolongation phase, includes the first 100 participants followed by an interim analysis to define the power of the study. The third phase is the continuation of the study up to maximum 600 participants included in total. Trial Status The current protocol version is COVIDENZA v2.0 as of September 10, 2020. Recruitment started July 29, 2020 and is presently in safety pause after the first exploration phase. Recruitment is anticipated to be complete by 31 December 2021. Trial registration Eudract number 2020-002027-10 ClinicalTrials.gov Identifier: NCT04475601, registered June 8, 2020 Full protocol The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

scholarly journals Short-Course Antibiotic Treatment Is Not Inferior to a Long-Course One in Acute Cholangitis: A Systematic Review

2018 ◽  
Vol 64 (2) ◽  
pp. 307-315 ◽  
Author(s):  
Benedek Tinusz ◽  
László Szapáry ◽  
Bence Paládi ◽  
Judit Tenk ◽  
Zoltán Rumbus ◽  
...  
Keyword(s):  
Systematic Review ◽  
Antibiotic Treatment ◽  
Acute Cholangitis ◽  
Short Course ◽  
Long Course

scholarly journals Unfractionated heparin in acute chest syndrome: a pilot feasibility randomized controlled trial of unfractionated heparin vs. standard of care in acute chest syndrome

2020 ◽  
Vol 6 (1) ◽  
Author(s):  
Craig D. Seaman ◽  
Enrico Novelli ◽  
Laura De Castro ◽  
Margaret V. Ragni
Keyword(s):  
Unfractionated Heparin ◽  
Large Scale ◽  
Controlled Trial ◽  
Standard Of Care ◽  
Phase Iii ◽  
Therapeutic Modality ◽  
Red Blood Cell Transfusion ◽  
Acute Chest Syndrome ◽  
Open Label ◽  
Randomized Controlled

Abstract Background Acute chest syndrome (ACS) is the leading cause of mortality in sickle cell disease (SCD). The pathogenesis of ACS is complex and not entirely understood with multiple etiologies likely contributing simultaneously. One particular etiology is pulmonary vascular occlusion due to thrombosis. Thus, anticoagulation is an attractive therapeutic modality. Methods This was a single-center, randomized controlled, open-label, pilot study to determine the feasibility of performing a larger multicenter phase III trial to assess the effects of unfractionated heparin (UFH) in ACS. Subjects were randomized within 24 h of diagnosis of ACS to one of two treatment arms, UFH, and standard of care (SOC), or no UFH and SOC. UFH was given intravenously for 7 days, or until discharge, if discharge was shorter than 7 days. SOC consisted of intravenous fluids, antibiotics, supplemental oxygen, analgesia, red blood cell transfusion, and exchange transfusion. Results From July 2014 to June 2018, a total of 7 patients underwent randomization (four patients received UFH in addition to SOC and 3 patients received SOC only). Two of the prespecified feasibility criteria were not met: the capacity to consent eligible individuals and the timely notification of hospitalized patients with ACS necessary to permit randomization within 24 h of diagnosis; thus, as a result of poor enrollment, the study was terminated early. The duration of hospitalization was 279.43 (SD 267.98) and 127.31 (SD 137.70) h in the UFH and SOC arms, respectively. The duration of hypoxemia, leukocytosis, fever, and moderate to severe pain was 117.52 (SD 60.52), 24.90 (SD 29.69), 117.52 (SD 60.52), and 117.52 (SD 60.52) h, respectively, in the UFH group, and 51.49 (SD 44.79), 0, 53.11 (SD 25.06), and 88.68 (SD 72.77) h, respectively, in the SOC group. No major bleeding was noted in either group. Conclusions Our study did not achieve prespecified feasibility criteria, resulting in poor enrollment and early termination, and serves to highlight some of the pitfalls experienced in clinical research in SCD. It did show the use of UFH without any major adverse events in 7 subjects. No future large-scale study is planned. Trials registration Registered at ClinicalTrials.gov (NCT #02098993) on March 28, 2014.

scholarly journals High dose oral and intravenous rifampicin for improved survival from adult tuberculous meningitis: a phase II open-label randomised controlled trial (the RifT study)

2018 ◽  
Vol 3 ◽  
pp. 83 ◽  
Author(s):  
Fiona V. Cresswell ◽  
Kenneth Ssebambulidde ◽  
Daniel Grint ◽  
Lindsey te Brake ◽  
Abdul Musabire ◽  
...  
Keyword(s):  
Randomised Controlled Trial ◽  
Phase Ii ◽  
Controlled Trial ◽  
Standard Of Care ◽  
Hiv Positive ◽  
Current Standard ◽  
Open Label ◽  
Dose Oral ◽  
Randomised Controlled ◽  
Positive Population

Background: Tuberculous meningitis (TBM) has 44% (95%CI 35-52%) in-hospital mortality with standard therapy in Uganda. Rifampicin, the cornerstone of TB therapy, has 70% oral bioavailability and ~10-20% cerebrospinal fluid (CSF) penetration.  With current WHO-recommended TB treatment containing 8-12mg/kg rifampicin, CSF rifampicin exposures frequently fall below the minimal inhibitory concentration for M. tuberculosis. Two Indonesian phase II studies, the first investigating intravenous rifampicin 600mg and the second oral rifampicin ~30mg/kg, found the interventions were safe and resulted in significantly increased CSF rifampicin exposures and a reduction in 6-month mortality in the investigational arms. Whether such improvements can be replicated in an HIV-positive population remains to be determined. Protocol: We will perform a phase II, open-label randomised controlled trial, comparing higher-dose oral and intravenous rifampicin with current standard of care in a predominantly HIV-positive population. Participants will be allocated to one of three parallel arms (I:I:I): (i) intravenous rifampicin 20mg/kg for 2-weeks followed by oral rifampicin 35mg/kg for 6-weeks; (ii) oral rifampicin 35mg/kg for 8-weeks; (iii) standard of care, oral rifampicin 10mg/kg/day for 8-weeks. Primary endpoints will be: (i) pharmacokinetic parameters in plasma and CSF; (ii) safety. We will also examine the effect of higher-dose rifampicin on survival time, neurological outcomes and incidence of immune reconstitution inflammatory syndrome. We will enrol 60 adults with suspected TBM, from two hospitals in Uganda, with follow-up to 6 months post-enrolment. Discussion: HIV co-infection affects the bioavailability of rifampicin in the initial days of therapy, risk of drug toxicity and drug interactions, and ultimately mortality from TBM. Our study aims to demonstrate, in a predominantly HIV-positive population, the safety and pharmacokinetic superiority of one or both investigational arms compared to current standard of care. The most favourable dose may ultimately be taken forward into an adequately powered phase III trial. Trial registration: ISRCTN42218549 (24th April 2018)

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