Tocilizumab Ameliorates the Hypoxia in COVID-19 Moderate Patients with Bilateral Pulmonary Lesions: A Randomized, Controlled, Open-Label, Multicenter Trial

MANAGEMENT OF ENDOCRINE DISEASE: Rituximab therapy for Graves’ orbitopathy – lessons from randomized control trials

Acta Endocrinologica ◽

10.1530/eje-16-0552 ◽

2017 ◽

Vol 176 (2) ◽

pp. R101-R109 ◽

Cited By ~ 40

Author(s):

Marius N Stan ◽

Mario Salvi

Keyword(s):

Multicenter Trial ◽

Clinical Activity ◽

Open Label ◽

Endocrine Disease ◽

Randomized Controlled ◽

Duration Of Disease ◽

Graves Orbitopathy ◽

Randomized Control ◽

Post Hoc

Rituximab (RTX) use in open-label series has been associated with very encouraging responses in patients with active and moderate-to-severe Graves’ orbitopathy (GO). Recently, randomized controlled trials of RTX have been performed in such patients to answer the question of clinical efficacy and the safety profile of this agent. That data, reported separately, focused on Clinical Activity Score (CAS) and indicated in one trial a strong benefit of RTX in comparison with IV glucocorticoids, whereas the other trial noted the absence of a benefit by comparison with placebo. The outcome was reanalyzed post hoc here, using EUGOGO criteria, and the results were not significantly different. The authors comment further on the differences between the two trials regarding populations treated, methodology, analysis of outcomes and the adverse effect profile of RTX. The populations treated appear different with younger patients, lower TRAb and shorter duration of disease prevalent in the Italian trial, all elements favoring a better response. Smoking, usually diminishing a response, was also more prevalent in some patients. The combined outcome proposed by EUGOGO revealed similar results with CAS regarding RTX efficacy; yet, it might be a more comprehensive outcome. The adverse events of concern relate mainly to the risk of DON, which seems to be increased by the use of RTX in a certain subset of patients. Based on available data, a multicenter trial using the EUGOGO-proposed outcomes might be the next best step to define the role of RTX in GO therapy.

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Study protocol: COmparison of the effect of treatment with Nonsteroidal anti-inflammatory drugs added to anti-tumour necrosis factor a therapy versus anti-tumour necrosis factor a therapy alone on progression of StrUctural damage in the spine over two years in patients with ankyLosing spondylitis (CONSUL) – an open-label randomized controlled multicenter trial

BMJ Open ◽

10.1136/bmjopen-2016-014591 ◽

2017 ◽

Vol 7 (6) ◽

pp. e014591 ◽

Cited By ~ 6

Author(s):

Fabian Proft ◽

Burkhard Muche ◽

Joachim Listing ◽

Valeria Rios-Rodriguez ◽

Joachim Sieper ◽

...

Keyword(s):

Ankylosing Spondylitis ◽

Tumour Necrosis Factor ◽

Tumour Necrosis ◽

Structural Damage ◽

Multicenter Trial ◽

Open Label ◽

Randomized Controlled ◽

Effect Of Treatment ◽

Inflammatory Drugs ◽

Necrosis Factor

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Optimization of sepsis therapy based on patient-specific digital precision diagnostics using next generation sequencing (DigiSep-Trial)—study protocol for a randomized, controlled, interventional, open-label, multicenter trial

Trials ◽

10.1186/s13063-021-05667-x ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Thorsten Brenner ◽

Annabell Skarabis ◽

Philip Stevens ◽

Jennifer Axnick ◽

Peter Haug ◽

...

Keyword(s):

Unit Length ◽

Bloodstream Infections ◽

Standard Of Care ◽

Multicenter Trial ◽

Intermediate Care ◽

Open Label ◽

Randomized Controlled ◽

Link Type ◽

Microbiological Analyses ◽

Generation Sequencing

Abstract Background Sepsis is triggered by an infection and represents one of the greatest challenges of modern intensive care medicine. With regard to a targeted antimicrobial treatment strategy, the earliest possible pathogen detection is of crucial importance. Until now, culture-based detection methods represent the diagnostic gold standard, although they are characterized by numerous limitations. Culture-independent molecular diagnostic procedures represent a promising alternative. In particular, the plasmatic detection of circulating, cell-free DNA by next-generation sequencing (NGS) has shown to be suitable for identifying disease-causing pathogens in patients with bloodstream infections. Methods The DigiSep-Trial is a randomized, controlled, interventional, open-label, multicenter trial characterizing the effect of the combination of NGS-based digital precision diagnostics with standard-of-care microbiological analyses compared to solely standard-of-care microbiological analyses in the clinical picture of sepsis/septic shock. Additional anti-infective expert consultations are provided for both study groups. In 410 patients (n = 205 per arm) with sepsis/septic shock, the study examines whether the so-called DOOR-RADAR (Desirability of Outcome Ranking/Response Adjusted for Duration of Antibiotic Risk) score (representing a combined endpoint including the criteria (1) intensive/intermediate care unit length of stay, (2) consumption of antibiotics, (3) mortality, and (4) acute kidney injury (AKI)) can be improved by an additional NGS-based diagnostic concept. We also aim to investigate the cost-effectiveness of this new diagnostic procedure. It is postulated that intensive/intermediate care unit length of stay, mortality rate, incidence of AKI, the duration of antimicrobial therapy as well as the costs caused by complications and outpatient aftercare can be reduced. Moreover, a significant improvement in patient’s quality of life is expected. Discussion The authors´ previous work suggests that NGS-based diagnostics have a higher specificity and sensitivity compared to standard-of-care microbiological analyses for detecting bloodstream infections. In combination with the here presented DigiSep-Trial, this work provides the optimal basis to establish a new NGS-driven concept as part of the national standard based on the best possible evidence. Trial registrations DRKS-ID DRKS00022782. Registered on August 25, 2020 ClinicalTrials.govNCT04571801. Registered October 1, 2020

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Favipiravir versus Arbidol for COVID-19: A Randomized Clinical Trial

10.1101/2020.03.17.20037432 ◽

2020 ◽

Cited By ~ 153

Author(s):

Chang Chen ◽

Yi Zhang ◽

Jianying Huang ◽

Ping Yin ◽

Zhenshun Cheng ◽

...

Keyword(s):

Recovery Rate ◽

Primary Outcome ◽

Safety Data ◽

Multicenter Trial ◽

Noninvasive Mechanical Ventilation ◽

Open Label ◽

Clinical Recovery ◽

Randomized Controlled ◽

Secondary Outcomes ◽

To Receive

AbstractBackgroundNo clinically proven effective antiviral strategy exists for the epidemic Coronavirus Disease 2019 (COVID-19).MethodsWe conducted a prospective, randomized, controlled, open-label multicenter trial involving adult patients with COVID-19. Patients were randomly assigned in a 1:1 ratio to receive conventional therapy plus Umifenovir (Arbidol) (200mg*3/day) or Favipiravir (1600mg*2/first day followed by 600mg*2/day) for 10 days. The primary outcome was clinical recovery rate of Day 7. Latency to relief for pyrexia and cough, the rate of auxiliary oxygen therapy (AOT) or noninvasive mechanical ventilation (NMV) were the secondary outcomes. Safety data were collected for 17 days.Results240 enrolled COVID-19 patients underwent randomization; 120 patients were assigned to receive Favipiravir (116 assessed), and 120 to receive Arbidol (120 assessed). Clinical recovery rate of Day 7 does not significantly differ between Favipiravir group (71/116) and Arbidol group (62/120) (P=0.1396, difference of recovery rate: 0.0954; 95% CI: -0.0305 to 0.2213). Favipiravir led to shorter latencies to relief for both pyrexia (difference: 1.70 days, P<0.0001) and cough (difference: 1.75 days, P<0.0001). No difference was observed of AOT or NMV rate (both P>0.05). The most frequently observed Favipiravir-associated adverse event was raised serum uric acid (16/116, OR: 5.52, P=0.0014).ConclusionsAmong patients with COVID-19, Favipiravir, compared to Arbidol, did not significantly improve the clinically recovery rate at Day 7. Favipiravir significantly improved the latency to relief for pyrexia and cough. Adverse effects caused Favipiravir are mild and manageable. This trial is registered with Chictr.org.cn (ChiCTR2000030254).

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Lessons Learned From a Randomized Controlled Trial of Short-Course Intravenous Antibiotic Therapy for Erysipelas and Cellulitis of the Lower Limb (Switch Trial)

Open Forum Infectious Diseases ◽

10.1093/ofid/ofz335 ◽

2019 ◽

Vol 6 (9) ◽

Cited By ~ 2

Author(s):

Marcus C Clarke ◽

Allen C Cheng ◽

James Gd Pollard ◽

Mark Birch ◽

Raquel U Cowan ◽

...

Keyword(s):

Lower Limb ◽

Controlled Trial ◽

Visual Assessment ◽

Multicenter Trial ◽

Antimicrobial Treatment ◽

Lessons Learned ◽

Response To Therapy ◽

Open Label ◽

Randomized Controlled ◽

Short Course

Abstract Background The diagnosis of cellulitis is made clinically without a gold standard diagnostic test, and cellulitis has many disease mimics. There is currently no consensus for optimal antimicrobial treatment duration or method of antimicrobial delivery. Methods This was a randomized controlled open-label multicenter trial to determine the safety and efficacy of 24 hours of intravenous (IV) therapy compared with ≥72 hours of IV therapy, both followed by oral therapy to a maximum of 7–10 days’ duration for the treatment of lower limb cellulitis. Results Over 40 months, 80 patients were recruited. Thirty-nine patients were assigned to 24 hours of IV antibiotics and 41 to ≥72 hours of IV antibiotics. The mean duration (range) of IV antibiotics in the 24-hour group was 25.5 (17–40) hours, and in the ≥72-hour group it was 78 (41.5–210) hours. Three patients in the 24-hour arm and 4 patients in the ≥72-hour arm were excluded from the analysis due to withdrawal from the trial. Analysis of the remaining patients revealed that 6 patients (4 in the intervention arm and 2 in the control arm) did not achieve an adequate response to therapy. Only 1 patient experienced self-limiting adverse effects of treatment. Conclusions The noninferiority of short-course IV therapy cannot be determined from this trial. Challenges included resource limitations for recruitment, misdiagnosis, participant withdrawal, and subjective responses to therapy based on visual assessment by treating clinicians. Further studies are needed to determine if short-course IV therapy is a suitable treatment option. Australia Council of Clinical Trials Registry No ACTRN12613001366741.

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