Query: IVIG COVID-19 Clinical trials

title: Hyperimmune anti COVID 19 IVIG (C IVIG) Therapy for Passive Immunization of Severe and Critically Ill COVID 19 Patients: A structured summary of a study protocol for a randomised controlled trial
abstract: The aim of this trial is to investigate the safety and clinical efficacy of passive immunization therapy through Hyperimmune anti COVID 19 Intravenous Immunoglobulin (C IVIG: 5% liquid formulation) on severe and critically ill patients with COVID 19.  This is a phase I/II single centre, randomised controlled, single blinded, superiority trial, through parallel group design with sequential assignment. Participants will be randomised either to receive both C IVIG and standard care or only standard care (4:1) Participants The study is mono centric with the participants including COVID19 infected individuals (positive SARS CoV 2 PCR on nasopharyngeal and/or oropharyngeal swabs) admitted in institute affiliated with Dow University Hospital, Dow University of Health Sciences, Karachi, Pakistan. Consenting patients above 18 years that are classified by the treating physician as severely ill i.e. showing symptoms of COVID 19 pneumonia; dyspnea, respiratory rate =30/min, blood oxygen saturation =93% PaO 2 /FiO 2 <300, and lung infiltrates >50% on CXR; or critically ill i.e. respiratory failure, septic shock, and multiple organ dysfunction or failure. Patients with reported IgA deficiency, autoimmune disorder, thromboembolic disorder, and allergic reaction to immunoglobulin treatment were excluded from study. Similarly, pregnant females, patients requiring two or more inotropic agents to maintain blood pressure and patients with acute or chronic kidney injury/failure, were also excluded from the study.  The study consists of four interventions and one comparator arm. All participants receive standard hospital care which includes airway support, anti viral medication, antibiotics, fluid resuscitation, hemodynamic support, steroids, painkillers, and anti pyretics. Randomised test patients will receive single dose of C IVIG in following four dosage groups: Group 1: 0.15g/Kg with standard hospital care Group 2: 0.2g/Kg with standard hospital care Group 3: 0.25g/Kg with standard hospital care Group 4: 0.3g/Kg with standard hospital care Group 5 (comparator) will receive standard hospital care only Main outcomes The primary outcomes are assessment and follow up of participants to observe 28 day mortality and, the level and duration of assisted ventilation during hospital stay, number of days to step down (shifting from ICU to isolation ward) number of days to hospital discharge, adverse events (Kidney failure, hypersensitivity with cutaneous or hemodynamic manifestations, aseptic meningitis, hemolytic anemia, leuko neutropenia, transfusion related acute lung injury (TRALI) during hospital stay, change in C Reactive Protein (CRP) levels, change in neutrophil lymphocyte ratio to monitor inflammation.  Consenting participants who fulfill the criteria are allocated to either intervention or comparator arm with a ratio of 4:1, using sequentially numbered opaque sealed envelope simple randomization method. The participant allocated for intervention will be sequentially assigned dosage group 1 4 in ascending order. Participants will not be recruited in the next dosage group before a set number of participants in one group (10) are achieved. Blinding (masking) Single blinded study, with participants blinded to allocation. Numbers to be randomised (sample size) Total 50 patients are randomised. The intervention arms consist of 40 participants divided in four groups of 10 participants while the comparator group consists of 10 patients.  Participants are being recruited. Recruitment started on June, 2020 and is estimated to primarily end on January, 2021.

title: Towards treatment planning of COVID 19: Rationale and hypothesis for the use of multiple immunosuppressive agents: Anti antibodies, immunoglobulins, and corticosteroids
abstract: The novel coronavirus, SARS CoV2, can cause a potentially fatal disease, COVID 19, in humans. Here, we will provide an overview of therapeutic options for COVID 19. Plasma from patients recovered from COVID 19 that contains antibodies against SARS CoV2 has shown promising results in patients with severe COVID 19. Also, IVIG, combined with moderate dose of corticosteroids, might improve patient outcomes. Evidence links COVID 19 to variable degrees of inflammation. Studies show that the use of corticosteroids might accelerate recovery from COVID 19. There are, however, no controlled clinical trials that show whether the use of corticosteroids can reduce COVID 19 related death. Also, the pro inflammatory cytokine IL6 is the best documented cytokine in COVID 19 correlated with severity, criticality, viral load, and prognosis of patients with COVID 19. Tocilizumab, a monoclonal antibody against IL6, could confer clinical benefit in patients with high IL6 levels. Essential elements that process SARS CoV2 cell entry and specific characteristics that allow SARS CoV2 to escape the immune system have the potential as targets for COVID 19 therapy.

title: Intravenous immunoglobulin immunotherapy for coronavirus disease 19 (COVID 19)
abstract: Intravenous immunoglobulin (IVIG) a pooled normal IgG from several thousand healthy donors and one of the commonly used immunotherapeutic molecules for the management of autoimmune and inflammatory diseases, has been explored for the treatment of coronavirus disease 19 (COVID 19) Although placebo controlled, double blind randomised clinical trials are lacking, current data from either retrospective, case series or open label randomised controlled trials provide an indicator that IVIG immunotherapy could benefit severe and critically ill COVID 19 patients. See alsoShao et al.

title: A consideration of convalescent plasma and plasma derivatives in the care of Severely ill patients with COVID 19
abstract: The pathogenesis and immunopathological damage of severe forms of COVID 19 resemble acute autoimmune disease sparked by SARS CoV 2, including an early systemic overproduction of proinflammatory cytokines. Such immunopathological features provide a rationale for the use of passive immunotherapy with convalescent plasma as a source of neutralizing anti viral antibodies and of anti inflammatory plasma components. While convalescent plasma therapy is now being evaluated in prospective clinical trials, we further consider the therapeutic potential of human hyper immune globulins, and of heterologous, engineered and monoclonal neutralizing antibodies as anti viral agents to treat COVID 19. Good medical practice procedures are still needed and is why we also discuss the potential use of polyclonal polyspecific immunoglobulins (IVIG) a therapeutic plasma derivative, with potent anti inflammatory activity, in severe forms of Covid 19.

title: Improving the efficacy of Chloroquine and Hydroxychloroquine against SARS CoV 2 may require Zinc additives A better synergy for future COVID 19 clinical trials.
abstract: The recent outbreak of coronavirus disease 2019 (COVID 19) is now officially declared as a pandemic by the World Health Organization. As of now, there is no known effective pharmaceutical agent against the SARS CoV 2 virus. However, several precautionary measures have been prescribed to prevent further spread of the virus, which include avoidance of social gatherings, proper handwashing, frequently disinfecting of used items and surfaces and so on. More recent studies have highlighted the possibility of treating patients infected with the novel SARS CoV 2 virus with chloroquine and hydroxychloroquine, of which mechanism of action is not completely understood. We seek to draw the attention of the scientific community to the possibility of drastically reducing the effects of the virus on the affected patients and improving clinical trials outcome through the synergistic action of zinc and chloroquine in patients suffering from the coronavirus disease.

title: COVID 19 Clinical Trials: A Primer for the Cardiovascular and Cardio Oncology Communities
abstract: The coronavirus disease 2019 (COVID 19) pandemic has resulted in a proliferation of clinical trials designed to slow the spread of severe acute respiratory syndrome coronavirus 2 (SARS CoV 2) Many therapeutic agents that are being used to treat patients with COVID 19 are repurposed treatments for influenza, Ebola, or for malaria that were developed decades ago and are unlikely to be familiar to the cardiovascular and cardio oncology communities. Here, the authors provide a foundation for cardiovascular and cardio oncology physicians on the front line providing care to patients with COVID 19, so that they may better understand the emerging cardiovascular epidemiology and the biological rationale for the clinical trials that are ongoing for the treatment of patients with COVID 19.

title: COVID 19 Clinical Trials
abstract: The COVID 19 pandemic has resulted in a proliferation of clinical trials that are designed to slow the spread of SARS CoV 2, the virus that causes COVID 19. The overwhelming majority of cardiovascular and cancer patients are at increased risk for SARS CoV 2 infection; accordingly, the cardiovascular and cardio oncology communities are playing a major role in caring for COVID 19 patients. Many of the therapeutic agents that are being used to treat patients with COVID 19 are repurposed treatments for influenza, drugs that were not effective in Ebola patients, or treatments for malaria that were developed decades ago, and are unlikely to be familiar to the cardiovascular and cardio oncology communities. Here we have provided a foundation for cardiovascular and cardio oncology physicians who are on the frontline providing care to COVID 19 patients, so that they can better understand the emerging cardiovascular epidemiology of COVID 19, as well as the biological rationale for the clinical trials that are ongoing for the treatment of COVID 19 patients.

title: Characteristics of COVID 19 Clinical Trials in China Based on the Registration Data on ChiCTR and ClinicalTrials.gov
abstract: This study aimed to evaluate the fundamental characteristics of coronavirus disease (COVID 19) clinical trials registered in China.  COVID 19 clinical trials registered in China were analyzed from databases on ChiCTR and ClinicalTrials.gov. The study designs, samples, primary end points, and intervention measures were evaluated.  In total, 262 intervention clinical trials were retrieved on March 10, 2020. Overall, 181 (69.1% trials involved two groups, 200 (76.3% trials were randomized parallel trials, 24 (9.2% trials were double blind, and 60.3% of trials included =100 participants. Sixty (22.9% trials considered symptom improvement as the primary endpoint and 43 (16.4% trials considered the rate or time at which the subjects became virus free as the primary endpoint. Of 262 intervention studies, chemical drugs and biological products were studied in 105 (40.1% intervention studies, of which antiviral drugs accounted for 15.3% and malaria drugs accounted for 8.4% of the studies. Among all trials, 27.9% of the studies used traditional Chinese medicine (TCM) 10.3% used cell therapy, and 5.0% used plasma therapy.  This study is the first snapshot of the landscape of COVID 19 clinical trials registered in China and provided the basic features of clinical trial designs for the treatment and prevention of COVID 19 to offer useful information to guide future clinical trials on COVID 19 in other countries.

title: The ethics of COVID 19 clinical trials: New considerations in a controversial area
abstract: In December 2019, coronavirus disease 2019 (COVID 19) was iscovered in Wuhan, Hubei province, China, which has caused evere illness and death.1 China is the most populous country in the orld with a population of 1.428 billion.2 With 11 million inhabtants, Wuhan is the largest transportation hub in central China, hich is known as Chicago of China.2,3 China has taken a series of ublic health interventions to control the epidemic. 3 The outbreak f COVID 19 has become a public health event of global concern.4 ue to its relatively high infectivity, the rapid progression of the isease and the lack of clear and effective treatment, it has caused nternational anxiety.4,5 In fact, it has also caused illness in a signifiant proportion of exposed medical personnel.6 Since identification f COVID 19 was confirmed in December 2019, the number of cases as shown an upward trend, and the epidemiological picture is hanging every day. With lack of any effective vaccine or drug urrently available, scientists and doctors are conducting a series f clinical studies involving affected patients.7,8 Although Chinese esearchers are struggling to find effective treatments and prevenive measures, and actively conduct clinical trials, one aspect of the linical trials has been surprisingly overlooked. That's the ethics f clinical trials. In 2016, the World Health Organization (WHO) eleased the "Guidance for Managing Ethical Issues in Infectious isease" to ensure the safety of participants during the outbreak of  The guidance notes that it is morally obligatory to conuct scientific research in a timely manner. As of April 5, 2020, the hinese Clinical Trials Registry (www.chictr.org.cn) has registered total of 556 COVID 19 clinical trials. Most of these studies are nterventional studies, which included randomized controlled trils (RCTs) followed by observational studies, diagnostic studies and ther types.10 Although the design of some studies may be flawed ue to the lack of time. However, it is the ethics of trials that need pecial attention. We have a few comments on this issue. On the one hand, the focus of ethical issues is the protection f the subjects' rights and interests. In clinical trials, the investiator or applicant should first consider how to protect the rights f the subjects. Specifically, the subjects' rights of voluntary paricipation, the right to know, the right to privacy, the right to

title: Ongoing non industry sponsored COVID 19 clinical trials in the first trimester of the pandemic: significant differences between the European and the USA approaches
abstract: The different features between non industry sponsored medicine trials conducted in Europe and the USA to treat COVID 19 patients registered in the first trimester of the pandemic are unknown.  A search was conducted on four databases looking for ongoing medicine randomized controlled trials (RCTs) and non RCTs registered current through April 25, 2020. All trials assessing medicines on prophylaxis, special populations, assessing non medicines and convalescent plasma, were excluded. Of each trial, medicines assessed, design, sample size, registration date, study start and study completion dates, and type of patients were registered.  106 trials were identified, 62 in Europe and 46 in the USA with two conducted in both regions. In Europe, 90% were on hospitalized patients, and 70% in the USA (p<0.01) Mean of the estimated time to completion were 7.8 and 13.6 (p<0.001) months for European and USA trials Multicenter trials were more frequent in Europe (63% than in the USA (41% (p=0.031) Masked RCTs were more frequently run in the USA than in Europe (p<0.001) RCTs on hospitalized patients were more commonly conducted in Europe (91% than in the USA (65% (p<0.01) Conclusions Features of early registered COVID 19 RCTs with medicines in Europe and America had remarkable differences.