Search Results Heading

MBRLSearchResults

mbrl.module.common.modules.added.book.to.shelf
Title added to your shelf!
View what I already have on My Shelf.
Oops! Something went wrong.
Oops! Something went wrong.
While trying to add the title to your shelf something went wrong :( Kindly try again later!
Are you sure you want to remove the book from the shelf?
Oops! Something went wrong.
Oops! Something went wrong.
While trying to remove the title from your shelf something went wrong :( Kindly try again later!
    Done
    Filters
    Reset
  • Discipline
      Discipline
      Clear All
      Discipline
  • Is Peer Reviewed
      Is Peer Reviewed
      Clear All
      Is Peer Reviewed
  • Item Type
      Item Type
      Clear All
      Item Type
  • Subject
      Subject
      Clear All
      Subject
  • Year
      Year
      Clear All
      From:
      -
      To:
  • More Filters
      More Filters
      Clear All
      More Filters
      Source
    • Language
1,228 result(s) for "Coronavirus Infections - physiopathology"
Sort by:
IL-6 Inhibitors in the Treatment of Serious COVID-19: A Promising Therapy?
At present, there are no proven agents for treatment of coronavirus disease (COVID-19). The available evidence has not allowed guidelines to clearly recommend any drugs outside the context of clinical trials. The novel coronavirus SARS-CoV-2 that causes COVID-19 invokes a hyperinflammatory state driven by multiple cells and mediators like interleukin (IL)-1, IL-6, IL-12, and IL-18, tumor necrosis factor alpha (TNFα), etc. Considering the proven role of cytokine dysregulation in causing this hyperinflammation in the lungs with IL-6 being a key driver, particularly in seriously ill COVID-19 patients, it is crucial to further explore selective cytokine blockade with drugs like the IL-6 inhibitors tocilizumab, sarilumab, and siltuximab. These targeted monoclonal antibodies can dampen the downstream IL-6 signaling pathways, which can lead to decreased cell proliferation, differentiation, oxidative stress, exudation, and improve clinical outcomes in patients with evident features of cytokine-driven inflammation like persistent fever, dyspnea and elevated markers. Preliminary evidence has come for tocilizumab from some small studies, and interim analysis of a randomized controlled trial; the latter also being available for sarilumab. International guidelines do include IL-6 inhibitors as one of the options available for severe or critically ill patients. There has been increased interest in evaluating these drugs with a series of clinical trials being registered and conducted in different countries. The level of investigation though perhaps needs to be further intensified as there is a need to focus on therapeutic options that can prove to be ‘life-saving’ as the number of COVID-19 fatalities worldwide keeps increasing alarmingly. IL-6 inhibitors could be one such treatment option, with generation of more evidence and completion of a larger number of systematic studies.
SARS-CoV-2 organising pneumonia: ‘Has there been a widespread failure to identify and treat this prevalent condition in COVID-19?’
Reviews of COVID-19 CT imaging along with postmortem lung biopsies and autopsies indicate that the majority of patients with COVID-19 pulmonary involvement have secondary organising pneumonia (OP) or its histological variant, acute fibrinous and organising pneumonia, both well-known complications of viral infections. Further, many publications on COVID-19 have debated the puzzling clinical characteristics of ‘silent hypoxemia’, ‘happy hypoxemics’ and ‘atypical ARDS’, all features consistent with OP. The recent announcement that RECOVERY, a randomised controlled trial comparing dexamethasone to placebo in COVID-19, was terminated early due to excess deaths in the control group further suggests patients present with OP given that corticosteroid therapy is the first-line treatment. Although RECOVERY along with other cohort studies report positive effects with corticosteroids on morbidity and mortality of COVID-19, treatment approaches could be made more effective given that secondary OP often requires prolonged duration and/or careful and monitored tapering of corticosteroid dose, with ‘pulse’ doses needed for the well-described fulminant subtype. Increasing recognition of this diagnosis will thus lead to more appropriate and effective treatment strategies in COVID-19, which may lead to a further reduction of need for ventilatory support and improved survival.
Artificial intelligence mobile health platform for early detection of COVID-19 in quarantine subjects using a wearable biosensor: protocol for a randomised controlled trial
IntroductionThere is an outbreak of COVID-19 worldwide. As there is no effective therapy or vaccine yet, rigorous implementation of traditional public health measures such as isolation and quarantine remains the most effective tool to control the outbreak. When an asymptomatic individual with COVID-19 exposure is being quarantined, it is necessary to perform temperature and symptom surveillance. As such surveillance is intermittent in nature and highly dependent on self-discipline, it has limited effectiveness. Advances in biosensor technologies made it possible to continuously monitor physiological parameters using wearable biosensors with a variety of form factors.ObjectiveTo explore the potential of using wearable biosensors to continuously monitor multidimensional physiological parameters for early detection of COVID-19 clinical progression.MethodThis randomised controlled open-labelled trial will involve 200–1000 asymptomatic subjects with close COVID-19 contact under mandatory quarantine at designated facilities in Hong Kong. Subjects will be randomised to receive a remote monitoring strategy (intervention group) or standard strategy (control group) in a 1:1 ratio during the 14 day-quarantine period. In addition to fever and symptom surveillance in the control group, subjects in the intervention group will wear wearable biosensors on their arms to continuously monitor skin temperature, respiratory rate, blood pressure, pulse rate, blood oxygen saturation and daily activities. These physiological parameters will be transferred in real time to a smartphone application called Biovitals Sentinel. These data will then be processed using a cloud-based multivariate physiology analytics engine called Biovitals to detect subtle physiological changes. The results will be displayed on a web-based dashboard for clinicians’ review. The primary outcome is the time to diagnosis of COVID-19.Ethics and disseminationEthical approval has been obtained from institutional review boards at the study sites. Results will be published in peer-reviewed journals.
A prospective, randomised, double blind placebo-controlled trial to evaluate the efficacy and safety of tocilizumab in patients with severe COVID-19 pneumonia (TOC-COVID): A structured summary of a study protocol for a randomised controlled trial
Objectives SARS-CoV2 infection leads to a concomitant pulmonary inflammation. This inflammation is supposed to be the main driver in the pathogenesis of lung failure (Acute Respiratory Distress Syndrome) in COVID-19. Objective of this study is to evaluate the efficacy and safety of a single dose treatment with Tocilizumab in patients with severe COVID-19. We hypothesize that Tocilizumab slows down the progression of SARS-CoV-2 induced pneumonia and inflammation. We expect an improvement in pulmonary function compared to placebo-treated patients. Desirable outcomes would be that tocilizumab reduces the number of days that patients are dependent on mechanical ventilation and reduces the invasiveness of breathing assistance. Furthermore, this treatment might result in fewer admissions to intensive care units. Next to these efficacy parameters, safety of a therapy with Tocilizumab in COVID-19 patients has to be monitored closely, since immunosuppression could lead to an increased rate of bacterial infections, which could negatively influence the patient’s outcome. Trial design Multicentre, prospective, 2-arm randomised (ratio 1:1), double blind, placebo-controlled trial with parallel group design. Participants Inclusion criteria Proof of SARS-CoV2 (Symptoms and positive polymerase chain reaction (PCR)) Severe respiratory failure: Ambient air SpO 2 ≤ 92% or Need of ≥ 6l O2/min or NIV (non-invasive ventilation) or IMV (invasive mechanical ventilation) Age ≥ 18 years Exclusion criteria Non-invasive or invasive mechanical ventilation ≥ 48 hours Pregnancy or breast feeding Liver injury or failure (AST/ALT ≥ 5x ULN) Leukocytes < 2 × 10 3 /μl Thrombocytes < 50 × 10 3 /μl Severe bacterial infection (PCT > 3ng/ml) Acute or chronic diverticulitis Immunosuppressive therapy (e.g. mycophenolate, azathioprine, methotrexate, biologicals, prednisolone >10mg/d; exceptions are: prednisolone ≤ 10mg/d, sulfasalazine or hydroxychloroquine) Known active or chronic tuberculosis Known active or chronic viral hepatitis Known allergic reactions to tocilizumab or its ingredients Life expectation of less than 1 year (independent of COVID-19) Participation in any other interventional clinical trial within the last 30 days before the start of this trial Simultaneous participation in other interventional trials (except for participation in COVID-19 trials) which could interfere with this trial; simultaneous participation in registry and diagnostic trials is allowed Failure to use one of the following safe methods of contraception: female condoms, diaphragm or coil, each used in combination with spermicides; intra-uterine device; hormonal contraception in combination with a mechanical method of contraception. The data collection of the primary follow up (28 days after randomisation) takes place during the hospital stay. Subsequently, a telephone interview on the quality of life is conducted after 6 and 12 months. Participants will be recruited from inpatients at ten medical centres in Germany. Intervention and comparator Intervention arm: Application of 8mg/kg body weight (BW) Tocilizumab i.v. once immediately after randomisation (12 mg/kg for patients with <30kg BW; total dose should not exceed 800 mg) AND conventional treatment. Control arm: Placebo (NaCl) i.v. once immediately after randomisation AND conventional treatment. Main outcomes Primary endpoint is the number of ventilator free days (d) (VFD) in the first 28 days after randomisation. Non-invasive ventilation (NIV), Invasive mechanical ventilation (IMV) and extracorporeal membrane oxygenation (ECMO) are defined as ventilator days. VFD’s are counted as zero if the patient dies within the first 28 days. Randomisation The randomisation code will be generated by the CTU (Clinical Trials Unit, ZKS Freiburg) using the following procedure to ensure that treatment assignment is unbiased and concealed from patients and investigator staff. Randomisation will be stratified by centre and will be performed in blocks of variable length in a ratio of 1:1 within each centre. The block lengths will be documented separately and will not be disclosed to the investigators. The randomisation code will be produced by validated programs based on the Statistical Analysis System (SAS). Blinding (masking) Participants, caregivers, and the study team assessing the outcomes are blinded to group assignment. Numbers to be randomised (sample size) 100 participants will be randomised to each group (thus 200 participants in total). Trial Status Protocol Version: V 1.2, 16.04.2020. Recruitment began 27th April 2020 and is anticipated to be completed by December 2020. Trial registration The trial was registered before trial start in trial registries (EudraCT: No. 2020-001408-41, registered 21st April 2020, and DRKS: No. DRKS00021238, registered 22nd April 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.
Effects of Ginger on clinical manifestations and paraclinical features of patients with Severe Acute Respiratory Syndrome due to COVID-19: A structured summary of a study protocol for a randomized controlled trial
Objectives We investigate the effects of Ginger, compared to the usual therapeutic regimen on clinical manifestations and paraclinical features in patients with confirmed COVID-19 that are moderately ill. Trial design This is a single center, randomized, double-blind, placebo-controlled clinical trial with parallel group design. Participants Inclusion criteria : 1. Patients admitted to Severe Acute Respiratory Syndrome (SARS) Departments at Shahid Mohammadi Hospital, Bandar Abbas, Iran 2. Age ≥18 years (weight ≥35 kg) 3. Hospitalized ≤48 hours 4. Confirmed SARS-CoV-2 diagnosis (Positive polymerase chain reaction (PCR)) 5. Moderate pneumonia and lung involvement in imaging 6. Signing informed consent and willingness of study participant to accept randomization to any assigned treatment arm Exclusion criteria : 1. Underlying diseases, including heart disease, chronic hypertension, severe renal failure, severe liver failure, and thyroid disorders 2. Use of warfarin, selective serotonin reuptake inhibitors (SSRIs), monoamine oxidase inhibitors (MAOIs), diuretics, corticosteroids, and antiarrhythmic drugs 3. Severe and critical pneumonia 4. History of known allergy to Ginger 5. Pregnancy and breastfeeding Intervention and comparator Intervention group : The standard treatment regimen for COVID-19 along with Ginger-based herbal tablets (Vomigone ®, Dineh Pharmaceutical Company, Iran) at a dose of 1000 mg three times a day for a period of seven days. Control group : The standard treatment for COVID-19 based on the Iranian Ministry of Health and Medical Education's protocol, along with Vomigone-like placebo tablets (Dineh Pharmaceutical Company, Iran) at a dose of two tablets three times a day for a period of seven days. Main outcomes The primary outcome is recovery rate of clinical symptoms, including fever, dry cough, tiredness, and GI symptoms as well as paraclinical features, including thrombocytopenia, lymphocytopenia, and C-reactive protein within seven days of randomization. Time to improvement of clinical and paraclinical features along with the incidence of serious adverse events are the secondary outcomes within seven days of randomization. Randomization An interactive web-based system will be used to allocate eligible participants, based on the inclusion and exclusion criteria, to one of the two study arms (in a 1:1 ratio) using block randomization. Blinding (masking) All study participants, research coordinators, clinicians, nurses, and investigators will be blinded to the group assignment. Numbers to be randomized (sample size) A total of 84 participants will be randomized into two groups of 42 patients. Trial Status The protocol is Version 1.0, May 23, 2020. Recruitment began July 21, 2020, and is anticipated to be completed by October 30, 2020. Trial registration This clinical trial has been registered in the Iranian Registry of Clinical Trials (IRCT). The registration number is “ IRCT20200506047323N1 ”. Registration date is 23 May 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.
Repair of Acute Respiratory Distress Syndrome by Stromal Cell Administration in COVID-19 (REALIST-COVID-19): A structured summary of a study protocol for a randomised, controlled trial
Objectives The primary objective of the study is to assess the safety of a single intravenous infusion of Mesenchymal Stromal Cells (MSCs) in patients with Acute Respiratory Distress Syndrome (ARDS) due to COVID-19. Secondary objectives are to determine the effects of MSCs on important clinical outcomes, as described below. Trial design REALIST COVID 19 is a randomised, placebo-controlled, triple blinded trial. Participants The study will be conducted in Intensive Care Units in hospitals across the United Kingdom. Patients with moderate to severe ARDS as defined by the Berlin definition, receiving invasive mechanical ventilation and with a diagnosis of COVID-19 based on clinical diagnosis or PCR test will be eligible. Patients will be excluded for the following reasons: more than 72 hours from the onset of ARDS; age < 16 years; patient known to be pregnant; major trauma in previous 5 days; presence of any active malignancy (other than non-melanoma skin cancer); WHO Class III or IV pulmonary hypertension; venous thromboembolism currently receiving anti-coagulation or within the past 3 months; patient receiving extracorporeal life support; severe chronic liver disease (Child-Pugh > 12); Do Not Attempt Resuscitation order in place; treatment withdrawal imminent within 24 hours; prisoners; declined consent; non-English speaking patients or those who do not adequately understand verbal or written information unless an interpreter is available; previously enrolled in the REALIST trial. Intervention and comparator Intervention: Allogeneic donor CD362 enriched human umbilical cord derived mesenchymal stromal cells (REALIST ORBCEL-C) supplied as sterile, single-use cryopreserved cell suspension of a fixed dose of 400 x10 6 cells in 40ml volume, to be diluted in Plasma-Lyte 148 to a total volume of 200mls for administration. Comparator (placebo): Plasma-Lyte 148 Solution for Infusion (200mls). The cellular product (REALIST ORBCEL-C) was developed and patented by Orbsen Therapeutics. Main outcomes The primary safety outcome is the incidence of serious adverse events. The primary efficacy outcome is Oxygenation Index (OI) at day 7. Secondary outcomes include: OI at days 4 and 14; respiratory compliance, driving pressure and PaO 2 /FiO 2 ratio (PF ratio) at days 4, 7 and 14; Sequential Organ Failure Assessment (SOFA) score at days 4, 7 and 14; extubation and reintubation; ventilation free days at day 28; duration of mechanical ventilation; length of ICU and hospital stay; 28-day and 90-day mortality. Randomisation After obtaining informed consent, patients will be randomised via a centralised automated 24-hour telephone or web-based randomisation system (CHaRT, Centre for Healthcare Randomised Trials, University of Aberdeen). Randomisation will be stratified by recruitment centre and by vasopressor use and patients will be allocated to REALIST ORBCEL-C or placebo control in a 1:1 ratio. Blinding (masking) The investigator, treating physician, other members of the site research team and participants will be blinded. The cell therapy facility and clinical trials pharmacist will be unblinded to facilitate intervention and placebo preparation. The unblinded individuals will keep the treatment information confidential. The infusion bag will be masked at the time of preparation and will be administered via a masked infusion set. Numbers to be randomised (sample size) A sample size of 60 patients with 30 patients randomised to the intervention and 30 to the control group. If possible, recruitment will continue beyond 60 patients to provide more accurate and definitive trial results. The total number of patients recruited will depend on the pandemic and be guided by the data monitoring and ethics committee (DMEC). Trial status REALIST Phase 1 completed in January 2020 prior to the COVID-19 pandemic. This was an open label dose escalation study of REALIST ORBCEL-C in patients with ARDS. The COVID-19 pandemic emerged as REALIST Phase 2 was planned to commence and the investigator team decided to repurpose the Phase 2 trial as a COVID-19 specific trial. This decision was discussed and approved by the Trial Steering Committee (TSC) and DMEC. Submissions were made to the Research Ethics Committee (REC) and MHRA to amend the protocol to a COVID-19 specific patient population and the protocol amendment was accepted by the REC on 27 th March 2020 and MHRA on 30 th March 2020 respectively. Other protocol changes in this amendment included an increase in the time of onset of ARDS from 48 to 72 hours, inclusion of clinical outcomes as secondary outcomes, the provision of an option for telephone consent, an indicative sample size and provision to continue recruitment beyond this indicative sample size. The current protocol in use is version 4.0 23.03.2020 (Additional file 1 ). Urgent Public Health status was awarded by the NIHR on 2 April 2020 and the trial opened to recruitment and recruited the first participant the same day. At the time of publication the trial was open to recruitment at 5 sites across the UK (Belfast Health and Social Care Trust, King’s College London, Guys and St Thomas’ Hospital London, Birmingham Heartlands Hospital and the Queen Elizabeth Hospital Birmingham) and 12 patients have been recruited across these sites. Additional sites are planned to open and appropriate approvals for these are being obtained. It is estimated recruitment will continue for 6 months. Trial registration ClinicalTrials.gov NCT 03042143 (Registered 3 Feb 2017). EudraCT 2017-000585-33 (Registered 28 Nov 2017). Full protocol The full protocol (version 4.0 23.03.2020) is attached as an additional file, accessible from the Trials website (Additional file 1 ). In the interest of 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. The study protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines (Additional file 2 ).
A parallel-group, multicenter randomized, double-blinded, placebo-controlled, phase 2/3, clinical trial to test the efficacy of pyridostigmine bromide at low doses to reduce mortality or invasive mechanical ventilation in adults with severe SARS-CoV-2 infection: the Pyridostigmine In Severe COvid-19 (PISCO) trial protocol
Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, the causative agent of coronavirus disease 2019 (COVID-19), may lead to severe systemic inflammatory response, pulmonary damage, and even acute respiratory distress syndrome (ARDS). This in turn may result in respiratory failure and in death. Experimentally, acetylcholine (ACh) modulates the acute inflammatory response, a neuro-immune mechanism known as the inflammatory reflex . Recent clinical evidence suggest that electrical and chemical stimulation of the inflammatory reflex may reduce the burden of inflammation in chronic inflammatory diseases. Pyridostigmine (PDG), an ACh-esterase inhibitor (i-ACh-e), increases the half-life of endogenous ACh, therefore mimicking the inflammatory reflex. This clinical trial is aimed at evaluating if add-on of PDG leads to a decrease of invasive mechanical ventilation and death among patients with severe COVID-19. Methods A parallel-group, multicenter, randomized, double-blinded, placebo-controlled, phase 2/3 clinical trial to test the efficacy of pyridostigmine bromide 60 mg/day P.O. to reduce the need for invasive mechanical ventilation and mortality in hospitalized patients with severe COVID-19. Discussion This study will provide preliminary evidence of whether or not -by decreasing systemic inflammation- add-on PDG can improve clinical outcomes in patients with severe COVID-19. Trial registration ClinicalTrials.gov NCT04343963 (registered on April 14, 2020).
Zilucoplan in patients with acute hypoxic respiratory failure due to COVID-19 (ZILU-COV): A structured summary of a study protocol for a randomised controlled trial
Objectives Zilucoplan (complement C5 inhibitor) has profound effects on inhibiting acute lung injury post COVID-19, and can promote lung repair mechanisms that lead to improvement in lung oxygenation parameters. The purpose of this study is to investigate the efficacy and safety of Zilucoplan in improving oxygenation and short- and long-term outcome of COVID-19 patients with acute hypoxic respiratory failure. Trial design This is a phase 2 academic, prospective, 2:1 randomized, open-label, multi-center interventional study. Participants Adult patients (≥18y old) will be recruited at specialized COVID-19 units and ICUs at 9 Belgian hospitals. The main eligibility criteria are as follows: 1) Inclusion criteria: a. Recent (≥6 days and ≤16 days) SARS-CoV-2 infection. b. Chest CT scan showing bilateral infiltrates within the last 2 days prior to randomisation. c. Acute hypoxia (defined as PaO 2 /FiO 2 below 350 mmHg or SpO2 below 93% on minimal 2 L/min supplemental oxygen). d. Signs of cytokine release syndrome characterized by either high serum ferritin, or high D-dimers, or high LDH or deep lymphopenia or a combination of those. 2) Exclusion criteria: e. Mechanical ventilation for more than 24 hours prior to randomisation. f. Active bacterial or fungal infection. g. History of meningococcal disease (due to the known high predisposition to invasive, often recurrent meningococcal infections of individuals deficient in components of the alternative and terminal complement pathways). Intervention and comparator Patients in the experimental arm will receive daily 32,4 mg Zilucoplan subcutaneously and a daily IV infusion of 2g of the antibiotic ceftriaxone for 14 days (or until hospital discharge, whichever comes first) in addition to standard of care. These patients will receive additional prophylactic antibiotics until 14 days after the last Zilucoplan dose: hospitalized patients will receive a daily IV infusion of 2g of ceftriaxone, discharged patients will switch to daily 500 mg of oral ciprofloxacin. The control group will receive standard of care and a daily IV infusion of 2g of ceftriaxone for 1 week (or until hospital discharge, whichever comes first), to control for the effects of antibiotics on the clinical course of COVID-19. Main outcomes The primary endpoint is the improvement of oxygenation as measured by mean and/or median change from pre-treatment (day 1) to post-treatment (day 6 and 15 or at discharge, whichever comes first) in PaO 2 /FiO 2 ratio, P(A-a)O 2 gradient and a/A PO 2 ratio. (PAO 2 = Partial alveolar pressure of oxygen, PaO 2 =partial arterial pressure of oxygen, FiO 2 =Fraction of inspired oxygen). Randomisation Patients will be randomized in a 2:1 ratio (Zilucoplan: control). Randomization will be done using an Interactive Web Response System (REDCap). Blinding (masking) In this open-label trial neither participants, caregivers, nor those assessing the outcomes will be blinded to group assignment. Numbers to be randomised (sample size) A total of 81 patients will be enrolled: 54 patients will be randomized to the experimental arm and 27 patients to the control arm. Trial Status ZILU-COV protocol Version 4.0 (June 10 2020). Participant recruitment started on June 23 2020 and is ongoing. Given the uncertainty of the pandemic, it is difficult to predict the anticipated end date. Trial registration The trial was registered on Clinical Trials.gov on May 11 th , 2020 (ClinicalTrials.gov Identifier: NCT04382755 ) and on EudraCT (Identifier: 2020-002130-33 ). 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.
Acupressure therapy and Liu Zi Jue Qigong for pulmonary function and quality of life in patients with severe novel coronavirus pneumonia (COVID-19): a study protocol for a randomized controlled trial
Background In December 2019, pneumonia associated with the 2019 novel coronavirus (COVID-19) emerged in Wuhan, China. The number of cases has increased rapidly. Patients with severe disease have a poor prognosis, and there are no effective therapies for COVID-19. Only rapid advice guidelines for symptomatic supportive care have been used. A traditional Chinese medicine rehabilitation (TCMR) program consisting of acupressure therapy and Liu Zi Jue Qigong can be used as a complementary therapy for COVID-19. Hence, we designed a randomized trial to evaluate the efficacy and advantages of TCMR for treating patients with severe COVID-19. Methods/design This is a parallel-design, two-arm, analyst assessor-blinded, randomized controlled trial. A total of 128 patients with COVID-19 aged from 20 to 80 years will be recruited and assigned randomly into a guideline therapy group and a guideline therapy plus TCMR group at a 1:1 ratio. Patients in both groups will receive guideline therapy. The patients in the intervention group will perform acupressure therapy and Liu Zi Jue Qigong exercises in addition to conventional treatments twice a day and will be persistent from admission to discharge. The primary outcome will be measured with the Modified Medical Research Council Dyspnea Scale, and the secondary outcomes will include the Activities of Daily Living Barthel Index Scale, Patient Health Questionnaire-9 Scale, and the Respiratory Symptoms Scale. The assessments of the clinical scales will be performed at three points (before treatment, the 7th day during hospitalization, and the discharge day). Adverse events will be noted and recorded for the safety evaluation. Discussion This trial will provide high-quality evidence of the value of TCMR, which consists of acupressure therapy and Liu Zi Jue Qigong exercises, for treating patients with severe COVID-19. Trial registration Chinese Clinical Trial Registry ChiCTR2000029994 . Registered on 18 February 2020
Flow controlled ventilation in Acute Respiratory Distress Syndrome associated with COVID-19: A structured summary of a study protocol for a randomised controlled trial
Objectives This study aims to demonstrate the positive effects on oxygenation of flow-controlled ventilation compared to conventionally ventilated patients in patients suffering from Acute respiratory distress syndrome (ARDS) associated with COVID-19.We define ARDS according to the “Berlin” definition integrating the oxygenation index (P/F ratio), the level of Positive End Expiratory Pressure (PEEP), radiological and clinical findings. Trial design This is a prospective, randomized (1:1 ratio), parallel group feasibility study in adult patients with proven COVID-19 associated ARDS. Participants All adult patients admitted to the ICU of Hamad Medical Corporation facilities in Qatar because of COVID-19 infection who develop moderate to severe ARDS are eligible. The inclusion criteria are above 18 years of age, proven COVID-19 infection, respiratory failure necessitating intubation and mechanical ventilation, ARDS with a P/F ratio of at least 200mmHg or less and a minimum PEEP 5cmH2O, BMI less 30 kg/ m2. The following exclusion criteria: no written consent, chronic respiratory disease, acute or chronic cardiovascular disease, pregnancy or need for special therapy (prone position and/or Extracorporeal membrane oxygenation). Intervention and comparator After randomisation, the group A patients will be ventilated with the test-device for 48 hours. The settings will be started with the pre-existing-PEEP. The upper pressure will be determined to achieve a tidal volume of 6 ml/kg lean body mass, while the respiratory rate will be set to maintain an arterial pH above 7.2. In group B, the ventilator settings will be adjusted by the attending ICU team in accordance with lung-protective ventilation strategy. All other treatment will be unchanged and according to our local policies/guidelines. Main outcomes The primary end point is PaO2. As this is a dynamic parameter, we will record it every 6-8 hours and analyse it sequentially. Randomisation The study team screens the ventilated patients who fulfil the inclusion criteria and randomise using a 1:1 allocation ratio after consenting using a closed envelope method. The latter were prepared and sealed in advance by an independent person. Blinding (masking) Due to the technical nature of the study (use of a specific ventilator) blinding is only possible for the data-analysts and the patients. Numbers to be randomised (sample size) The sample size calculation based on the assumption of an effect size (change in PaO2) of 1.5 SDS in the primary endpoint (PaO2), an intended power of 80%, an alpha error of 5% and an equal sample ratio results in n=7 patients needed to treat. However, to compensate for dropouts we will include 10 patients in each group, which means in total 20 patients. Trial Status The local registration number is MRC-05-018 with the protocol version number 3. The date of approval is 14 th April 2020. Recruitment began 28th May 2020 and is expected to end in September 2020. Trial registration The protocol was registered before starting subject recruitment under the title: “Flow controlled ventilation in ARDS associated with COVID-19” in ClinicalTrials.org with the registration number: NCT04399317 . Registered on 22 May 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.