Dataset Information

Annexin A5 in Patients With Severe COVID-19 Disease: A Single-Center, Randomized, Double-Blind, Placebo-Controlled Feasibility Trial.

ABSTRACT:

Objectives

To evaluate the study design and feasibility of drug administration and safety in a randomized clinical trial of recombinant human annexin A5 (SY-005), a constitutively expressed protein with anti-inflammatory, antiapoptotic, and anticoagulant properties, in patients with severe coronavirus disease 2019 (COVID-19).

Design

Double-blind, randomized clinical trial.

Setting

Two ICUs at an academic medical center.

Patients/subjects

Adults admitted to the ICU with a confirmed diagnosis of COVID-19 and requiring ventilatory or vasopressor support.

Interventions

SY-005, a recombinant human annexin A5, at 50 or 100 µg/kg IV every 12 hours for 7 days.

Measurements and main results

We enrolled 18 of the 55 eligible patients (33%) between April 21, 2021, and February 3, 2022. We administered 82% (196/238) of the anticipated doses of study medication and 86% (169/196) were given within 1 hour of the scheduled time. There were no drug-related serious adverse events. We captured 100% of the data that would be required for measuring clinical outcomes in a phase 2 or 3 trial.

Limitations

The small sample size was a result of decreasing admissions of patients with COVID-19, which triggered a stopping rule for the trial.

Conclusions

Although enrollment was low, administration of SY-005 to critically ill patients with COVID-19 every 12 hours for up to 7 days was feasible and safe. Further clinical trials of annexin A5 for the treatment of COVID-19 are warranted. Given reduction of severe COVID-19 disease, future studies should explore the safety and effectiveness of SY-005 use in non-COVID-related sepsis.

SUBMITTER: Martin CM

PROVIDER: S-EPMC10558223 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature

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Publications

Annexin A5 in Patients With Severe COVID-19 Disease: A Single-Center, Randomized, Double-Blind, Placebo-Controlled Feasibility Trial.

Martin Claudio M CM Slessarev Marat M Campbell Eileen E Basmaji John J Ball Ian I Fraser Douglas D DD Leligdowicz Aleksandra A Mele Tina T Priestap Fran F Tschirhart Brent J BJ Bentall Tracey T Lu Xiangru X Feng Qingping Q

Critical care explorations 20231005 10

<h4>Objectives</h4>To evaluate the study design and feasibility of drug administration and safety in a randomized clinical trial of recombinant human annexin A5 (SY-005), a constitutively expressed protein with anti-inflammatory, antiapoptotic, and anticoagulant properties, in patients with severe coronavirus disease 2019 (COVID-19).<h4>Design</h4>Double-blind, randomized clinical trial.<h4>Setting</h4>Two ICUs at an academic medical center.<h4>Patients/subjects</h4>Adults admitted to the ICU wi ...[more]

PMID: 37811130

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Project description:ObjectiveTo confirm the rapid onset anti-suicidal benefits of ketamine in the short term and at six weeks, overall and according to diagnostic group.DesignProspective, double blind, superiority, randomised placebo controlled trial.SettingSeven French teaching hospitals between 13 April 2015 and 12 March 2019.Eligibility criteria for participantsAged 18 or older with current suicidal ideation, admitted to hospital voluntarily. Exclusion criteria included a history of schizophrenia or other psychotic disorders, substance dependence, and contraindications for ketamine.Participants156 participants were recruited and randomised to placebo (n=83) or ketamine (n=73), stratified by centre and diagnosis: bipolar, depressive, or other disorders.InterventionTwo 40 minute intravenous infusions of ketamine (0.5 mg/kg) or placebo (saline) were administered at baseline and 24 hours, in addition to usual treatment.Main outcome measuresThe primary outcome was the rate of patients in full suicidal remission at day 3, according to the scale for suicidal ideation total score ≤3. Analyses were conducted on an intention-to-treat basis.ResultsMore participants receiving ketamine reached full remission of suicidal ideas at day 3 than those receiving placebo: 46 (63.0%) of 83 participants in the ketamine arm and 25 (31.6%) of 73 in the placebo arm (odds ratio 3.7 (95% confidence interval 1.9 to 7.3), P<0.001). This effect differed according to the diagnosis (treatment: P<0.001; interaction: P=0.02): bipolar (odds ratio 14.1 (95% confidence interval 3.0 to 92.2), P<0.001), depressive (1.3 (0.3 to 5.2), P=0.6), or other disorders (3.7 (0.9 to 17.3, P=0.07)). Side effects were limited. No manic or psychotic symptom was seen. Moreover, a mediating effect of mental pain was found. At week 6, remission in the ketamine arm remained high, although non-significantly versus placebo (69.5% v 56.3%; odds ratio 0.8 (95% confidence interval 0.3 to 2.5), P=0.7).ConclusionsThe findings indicate that ketamine is rapid, safe in the short term, and has persistent benefits for acute care in suicidal patients. Comorbid mental disorders appear to be important moderators. An analgesic effect on mental pain might explain the anti-suicidal effects of ketamine.Trial registrationClinicalTrials.gov NCT02299440.

Dataset Information

Annexin A5 in Patients With Severe COVID-19 Disease: A Single-Center, Randomized, Double-Blind, Placebo-Controlled Feasibility Trial.

Objectives

Design

Setting

Patients/subjects

Interventions

Measurements and main results

Limitations

Conclusions

Publications

Annexin A5 in Patients With Severe COVID-19 Disease: A Single-Center, Randomized, Double-Blind, Placebo-Controlled Feasibility Trial.

Similar Datasets

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