scholarly journals Randomised Controlled Trial of Intravenous Nafamostat Mesylate in COVID pneumonitis: Phase 1b/2a Experimental Study to Investigate Safety, Pharmacokinetics and Pharmacodynamics

2021 ◽  
Author(s):  
Tom M. Quinn ◽  
Erin E. Gaughan ◽  
Annya Bruce ◽  
Jean Antonelli ◽  
Richard O’Connor ◽  
...  
Keyword(s):  
Randomised Controlled Trial ◽  
Antiviral Activity ◽  
Immune Cell ◽  
Controlled Trial ◽  
Hospitalised Patients ◽  
Secondary Endpoints ◽  
Repurposed Drugs ◽  
Anti Inflammatory ◽  
Randomised Controlled ◽  
Nafamostat Mesylate

ABSTRACTDespite the success of vaccines and selected repurposed treatments, COVID-19 is likely to remain a global health problem and further chemotherapeutics are required. Many repurposed drugs have progressed rapidly to Phase 2 and 3 trials without characterisation of Pharmacokinetics (PK)/Pharmacodynamics (PD) including safety in COVID-19. One such drug is Nafamostat Mesylate (Nafamostat), a synthetic serine protease inhibitor with anticoagulant and anti-inflammatory properties. Preclinical data has demonstrated that it is has potent antiviral activity against SARS-CoV-2 by directly inhibiting the transmembrane protease serine 2 (TMPRSS2) dependent stage of host cell entry.MethodsWe present the findings of a phase Ib/II open label, platform randomised controlled trial (RCT), exploring the safety of intravenous Nafamostat in hospitalised patients with confirmed COVID-19 pneumonitis. Patients were assigned randomly to standard of care (SoC), Nafamostat or an alternative therapy. Secondary endpoints included clinical endpoints such as number of oxygen free days and clinical improvement/ deterioration, PK/PD, thromboelastometry, D Dimers, cytokines, immune cell flow cytometry and viral load.ResultsData is reported from 42 patients, 21 of which were randomly assigned to receive intravenous Nafamostat. The Nafamostat group developed significantly higher plasma creatinine levels, more adverse events and a lower number of oxygen free days. There were no other statistically significant differences in the primary or secondary endpoints between Nafamostat and SoC. PK data demonstrated that intravenous Nafamostat was rapidly broken down to inactive metabolites. We observed an antifibrinolytic profile, and no significant anticoagulant effects in thromboelastometry. Participants in the Nafamostat group had higher D Dimers compared to SoC. There were no differences in cytokine profile and immune cell phenotype and viral loads between the groups.ConclusionIn hospitalised patients with COVID-19, we did not observe evidence of anti-inflammatory, anticoagulant or antiviral activity with intravenous Nafamostat. Given the number of negative trials with repurposed drugs, our experimental medicine trial highlights the value of PK/PD studies prior to selecting drugs for efficacy trials. Given the mechanism of action, further evaluation of Nafamostat delivered via a different route may be warranted. This trial demonstrates the importance of experimental trials in new disease entities such as COVID-19 prior to selecting drugs for larger trials.

scholarly journals Nurse-based secondary preventive follow-up by telephone reduced recurrence of cardiovascular events: a randomised controlled trial

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Anna-Lotta Irewall ◽  
Anders Ulvenstam ◽  
Anna Graipe ◽  
Joachim Ögren ◽  
Thomas Mooe
Keyword(s):  
Randomised Controlled Trial ◽  
Primary Endpoint ◽  
Cardiovascular Events ◽  
Controlled Trial ◽  
Control Group ◽  
Coronary Syndrome ◽  
Secondary Endpoints ◽  
Randomised Controlled

AbstractEnhanced follow-up is needed to improve the results of secondary preventive care in patients with established cardiovascular disease. We examined the effect of long-term, nurse-based, secondary preventive follow-up by telephone on the recurrence of cardiovascular events. Open, randomised, controlled trial with two parallel groups. Between 1 January 2010 and 31 December 2014, consecutive patients (n = 1890) admitted to hospital due to stroke, transient ischaemic attack (TIA), or acute coronary syndrome (ACS) were included. Participants were randomised (1:1) to nurse-based telephone follow-up (intervention, n = 944) or usual care (control, n = 946) and followed until 31 December 2017. The primary endpoint was a composite of stroke, myocardial infarction, cardiac revascularisation, and cardiovascular death. The individual components of the primary endpoint, TIA, and all-cause mortality were analysed as secondary endpoints. The assessment of outcome events was blinded to study group assignment. After a mean follow-up of 4.5 years, 22.7% (n = 214) of patients in the intervention group and 27.1% (n = 256) in the control group reached the primary composite endpoint (HR 0.81, 95% CI 0.68–0.97; ARR 4.4%, 95% CI 0.5–8.3). Secondary endpoints did not differ significantly between groups. Nurse-based secondary preventive follow-up by telephone reduced the recurrence of cardiovascular events during long-term follow-up.

scholarly journals Home treatment of COPD exacerbation selected by DECAF score: a non-inferiority, randomised controlled trial and economic evaluation

Thorax ◽  
2018 ◽  
Vol 73 (8) ◽  
pp. 713-722 ◽  
Author(s):  
Carlos Echevarria ◽  
Joanne Gray ◽  
Tom Hartley ◽  
John Steer ◽  
Jonathan Miller ◽  
...  
Keyword(s):  
Randomised Controlled Trial ◽  
Length Of Stay ◽  
Controlled Trial ◽  
Prognostic Score ◽  
Cost Effective ◽  
Low Risk ◽  
Copd Exacerbation ◽  
Hospitalised Patients ◽  
Life Years ◽  
Randomised Controlled

BackgroundPrevious models of Hospital at Home (HAH) for COPD exacerbation (ECOPD) were limited by the lack of a reliable prognostic score to guide patient selection. Approximately 50% of hospitalised patients have a low mortality risk by DECAF, thus are potentially suitable.MethodsIn a non-inferiority randomised controlled trial, 118 patients admitted with a low-risk ECOPD (DECAF 0 or 1) were recruited to HAH or usual care (UC). The primary outcome was health and social costs at 90 days.ResultsMean 90-day costs were £1016 lower in HAH, but the one-sided 95% CI crossed the non-inferiority limit of £150 (CI −2343 to 312). Savings were primarily due to reduced hospital bed days: HAH=1 (IQR 1–7), UC=5 (IQR 2–12) (P=0.001). Length of stay during the index admission in UC was only 3 days, which was 2 days shorter than expected. Based on quality-adjusted life years, the probability of HAH being cost-effective was 90%. There was one death within 90 days in each arm, readmission rates were similar and 90% of patients preferred HAH for subsequent ECOPD.ConclusionHAH selected by low-risk DECAF score was safe, clinically effective, cost-effective, and preferred by most patients. Compared with earlier models, selection is simpler and approximately twice as many patients are eligible. The introduction of DECAF was associated with a fall in UC length of stay without adverse outcome, supporting use of DECAF to direct early discharge.Trial registration numberRegistered prospectively ISRCTN29082260.

scholarly journals Securing All intraVenous devices Effectively in hospitalised patients—the SAVE trial: study protocol for a multicentre randomised controlled trial

BMJ Open ◽  
2015 ◽  
Vol 5 (9) ◽  
pp. e008689 ◽  
Author(s):  
Claire M Rickard ◽  
Nicole Marsh ◽  
Joan Webster ◽  
E Geoffrey Playford ◽  
Matthew R McGrail ◽  
...  
Keyword(s):  
Randomised Controlled Trial ◽  
Study Protocol ◽  
Controlled Trial ◽  
Hospitalised Patients ◽  
Randomised Controlled

scholarly journals Anti-inflammatory effects of adjunctive macrolide treatment in adults admitted to hospital with influenza: an open-label, randomised controlled trial

The Lancet ◽  
2017 ◽  
Vol 390 ◽  
pp. S2 ◽  
Author(s):  
Nelson Lee ◽  
Chun-Kwok Wong ◽  
Martin C W Chan ◽  
Esther S L Yeung ◽  
Wilson W S Tam ◽  
...  
Keyword(s):  
Randomised Controlled Trial ◽  
Controlled Trial ◽  
Open Label ◽  
Anti Inflammatory ◽  
Randomised Controlled

scholarly journals Convalescent plasma for treatment of COVID-19: study protocol for an open randomised controlled trial in Sweden

BMJ Open ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. e048337
Author(s):  
Joakim Dillner ◽  
Johan Ursing
Keyword(s):  
Randomised Controlled Trial ◽  
Standard Care ◽  
Controlled Trial ◽  
Ethical Review ◽  
Block Randomisation ◽  
Ethical Approval ◽  
Registration Number ◽  
Secondary Endpoints ◽  
Randomised Controlled ◽  
Antibody Levels

IntroductionAlthough there are many studies on the use of convalescent plasma (CP) for treatment of COVID-19, it is not clear (1) which groups of patients may benefit, (2) what dose of plasma to give, or (3) which antibody levels the plasma should contain. Previous phase I/II studies and literature review suggest that CP should only be given to patients with viraemia, that a daily infusion should be given until the patient becomes virus free and that the neutralising antibody titre should preferably be >1:640Methods and analysisAn open randomised controlled trial enrolling patients with COVID-19, who must be SARS-CoV-2 positive in both airway and blood samples and admitted to a study hospital. Block randomisation 2:1 is to either 200 mL CP (preferably titre ≥1/640) daily for up to 10 days (until virus negative in blood) plus standard care or standard care only (control arm). The primary endpoint is mortality by day 28 after study inclusion. Secondary endpoints include mortality by day 60 and doses of plasma needed to clear viraemia. Assuming a reduced mortality of approximately 30% by the CP therapy and 85%–88% survival in the control arm, approximately 600 participants will be enrolled to the CP therapy arm and 300 participants to the control arm.Ethics and disseminationEthical approval has been granted by the Swedish Ethical Review Authority (reference: 2020-06277). Results from this trial will be compiled in a clinical study report, disseminated via journal articles and communicated to stakeholders.Trial registration numberNCT04649879.

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