scholarly journals Clinical trials for treatment or prevention of COVID-19. A review of Clinicaltrials.gov.

F1000Research ◽  
2021 ◽  
Vol 9 ◽  
pp. 823
Author(s):  
Martha Fors ◽  
Paloma González
Keyword(s):  
Clinical Trials ◽  
Phase Ii ◽  
Randomized Trials ◽  
Descriptive Study ◽  
Therapeutic Approaches ◽  
Open Label ◽  
Disease Treatment ◽  
Cross Sectional ◽  
Ongoing Research ◽  
Antimalarial Agents

Background: Coronavirus disease 2019 (COVID-19) has rapidly progressed into the worst pandemic in recent years. There are currently no approved therapies to treat the disease. Several clinical trials are being conducted to evaluate therapeutic approaches. Methods: We conducted a cross-sectional descriptive study to examine the main characteristics of COVID-19-related clinical interventional trials registered with ClinicalTrials.gov  from January to March 27th, 2020. . Results: We included 519 trials, 57.6% were phase II or III, open-label and randomized trials. Disease treatment was evaluated in 75.5% of trials, while prevention was evaluated in 12.1%. A total of 243 trials were listed as recruiting, and 42.4% were not yet recruiting. Approximately 20% of the analyzed trials are investigating antimalarial agents, while 10.2% are studying the use of convalescent plasma to treat the disease. Antiretrovirals, monoclonal antibodies, the use of stem cells, nitric oxide gases and vaccines are the most commonly evaluated therapies. As of the publication of this review, none of the clinical trials had uploaded results. Conclusions: ClinicalTrials.gov is an important database that contains ongoing research trials on COVID-19This study quantifies the outcomes of COVID-19-related clinical trials.  More than 500 studies have been  analyzed finding that most of these studies are interventional clinical trials  Phase II or III evaluating drugs or biological agents for the prevention or treating COVID-19.

scholarly journals Who is making clinical trials for treatment or prevention of COVID-19? A review of Clinicaltrials.gov, May 2020

F1000Research ◽  
2020 ◽  
Vol 9 ◽  
pp. 823
Author(s):  
Martha Fors ◽  
Paloma González
Keyword(s):  
Nitric Oxide ◽  
Clinical Trials ◽  
Randomized Trials ◽  
Descriptive Study ◽  
Therapeutic Approaches ◽  
Open Label ◽  
Disease Treatment ◽  
Cross Sectional ◽  
Ongoing Research ◽  
Antimalarial Agents

Background: Coronavirus disease 2019 (COVID-19) has rapidly progressed into the worst pandemic in recent years. There are currently no approved therapies to treat the disease. Several clinical trials are being conducted to evaluate therapeutic approaches. Methods: We conducted a cross-sectional descriptive study to examine the main characteristics of COVID-19-related clinical interventional trials registered with ClinicalTrials.gov until May 15th, 2020. Results: We included 519 trials, most of which were phase II or III, open-label and randomized trials. Disease treatment was evaluated in 75.5% of trials, while prevention was evaluated in 12.1%. A total of 243 trials were listed as recruiting, and 42.4% were not yet recruiting. Approximately 20% of the analyzed trials are investigating antimalarial agents, while 10.2% are studying the use of convalescent plasma to treat the disease. Antiretrovirals, monoclonal antibodies, the use of stem cells, nitric oxide gases and vaccines are the most commonly evaluated therapies. As of the publication of this review, none of the clinical trials had uploaded results. Conclusions: ClinicalTrials.gov is an important database that contains ongoing research trials on COVID-19, a disease that is of vital importance. This study quantifies the outcomes of COVID-19-related clinical trials. The safety and effectiveness of many therapeutic approaches are investigated to fight this disease.

Two-stage seamless transition design from open-label single-arm to randomized double-arm clinical trials

2016 ◽  
Vol 27 (1) ◽  
pp. 158-171 ◽  
Author(s):  
Haolun Shi ◽  
Guosheng Yin
Keyword(s):  
Clinical Trials ◽  
Sample Size ◽  
Phase Ii ◽  
Therapeutic Effects ◽  
Operating Characteristics ◽  
Phase Ii Trials ◽  
Open Label ◽  
Two Stage ◽  
Trade Offs ◽  
Experimental Drug

Conventional phase II clinical trials use either a single- or multi-arm comparison scheme to examine the therapeutic effects of the experimental drug. Both single- and multi-arm evaluations have their own merits; for example, single-arm phase II trials are easy to conduct and often require a smaller sample size, while multiarm trials are randomized and typically lead to a more objective comparison. To bridge the single- and double-arm schemes in one trial, we propose a two-stage design, in which the first stage takes a single-arm comparison of the experimental drug with the standard response rate (no concurrent treatment) and the second stage imposes a two-arm comparison by adding an active control arm. The design is calibrated using a new concept, the detectable treatment difference, to balance the trade-offs between futility termination, power, and sample size. We conduct extensive simulation studies to examine the operating characteristics of the proposed method and provide an illustrative example of our design.

scholarly journals Definitions and elements of endpoints in phase III randomized trials for the treatment of COVID-19: a cross-sectional analysis of trials registered in ClinicalTrials.gov

Trials ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Kentaro Sakamaki ◽  
Yukari Uemura ◽  
Yosuke Shimizu
Keyword(s):  
Clinical Trials ◽  
Sample Size ◽  
Outcome Measures ◽  
Randomized Trials ◽  
Clinical Course ◽  
Time Frame ◽  
Phase Iii ◽  
Cross Sectional ◽  
Cross Sectional Analysis ◽  
Sectional Analysis

Abstract Background There are several challenges in designing clinical trials for the treatment of novel infectious diseases, such as COVID-19. In particular, the definition of endpoints related to the severity, time frame, and clinical course remains unclear. Therefore, we conducted a cross-sectional analysis of phase III randomized trials for COVID-19 registered at ClinicalTrials.gov. Methods We collected the data from ClinicalTrials.gov on March 31, 2021, by specifying the following search conditions under Advanced Search: Condition or disease: (COVID-19) OR (SARS-CoV-2); Study type: Interventional Studies; Study Results: All Studies; Recruitment: Not yet recruiting, Recruiting, Enrolling by invitation, Active, Not recruiting, Suspended, Completed; Sex: All; and Phase: Phase 3. From the downloaded search results, we selected trials that met the following criteria: Primary Purpose: Treatment; Allocation: Randomized. We manually transcribed information not included in the downloaded file, such as Primary Outcome Measures, Secondary Outcome Measures, Time Frame, and Inclusion Criteria. In the analysis, we examined primary and secondary endpoints in trials with severe and non-severe patients, including the types of endpoints, time frame, clinical course, and sample size. Results A total of 406 trials were included in the analysis. The median numbers of endpoints in trials with severe and non-severe patients were 9 and 7, respectively. Approximately 25% of the trials used multiple primary endpoints. Regardless of the type of endpoint, the time frames were longer in the trials with severe patients than in the trials with non-severe patients. In the evaluation of the clinical course, worsening was often considered in binary endpoints, and improvement was considered in time-to-event endpoints. The sample size was the largest in clinical trials using binary endpoints. Conclusions Endpoints can differ with respect to severity, and the clinical course and time frame are important for defining endpoints. This study provides information that can facilitate the achievement of a consensus for the endpoints in evaluating COVID-19 treatments.

scholarly journals The TRAIL in the Treatment of Human Cancer: An Update on Clinical Trials

2021 ◽  
Vol 8 ◽  
Author(s):  
Martin Snajdauf ◽  
Klara Havlova ◽  
Jiri Vachtenheim ◽  
Andrej Ozaniak ◽  
Robert Lischke ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Phase Ii ◽  
Apoptotic Cell ◽  
Human Cancer ◽  
Phase Iii ◽  
Current Status ◽  
Therapeutic Approaches ◽  
Phase Iii Clinical Trials ◽  
Phase Ii Clinical Trials ◽  
Novel Drugs

TRAIL (tumor-necrosis factor related apoptosis-inducing ligand, CD253) and its death receptors TRAIL-R1 and TRAIL-R2 selectively trigger the apoptotic cell death in tumor cells. For that reason, TRAIL has been extensively studied as a target of cancer therapy. In spite of the promising preclinical observations, the TRAIL–based therapies in humans have certain limitations. The two main therapeutic approaches are based on either an administration of TRAIL-receptor (TRAIL-R) agonists or a recombinant TRAIL. These approaches, however, seem to elicit a limited therapeutic efficacy, and only a few drugs have entered the phase II clinical trials. To deliver TRAIL-based therapies with higher anti-tumor potential several novel TRAIL-derivates and modifications have been designed. These novel drugs are, however, mostly preclinical, and many problems continue to be unraveled. We have reviewed the current status of all TRAIL-based monotherapies and combination therapies that have reached phase II and phase III clinical trials in humans. We have also aimed to introduce all novel approaches of TRAIL utilization in cancer treatment and discussed the most promising drugs which are likely to enter clinical trials in humans. To date, different strategies were introduced in order to activate anti-tumor immune responses with the aim of achieving the highest efficacy and minimal toxicity.In this review, we discuss the most promising TRAIL-based clinical trials and their therapeutic strategies.

scholarly journals Treatment options in unresectable soft tissue and bone sarcoma of the extremities and pelvis – a systematic literature review

2020 ◽  
Vol 5 (11) ◽  
pp. 799-814
Author(s):  
Maria Anna Smolle ◽  
Joanna Szkandera ◽  
Dimosthenis Andreou ◽  
Emanuela Palmerini ◽  
Marko Bergovec ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Phase Ii ◽  
Randomized Trials ◽  
Randomized Clinical Trials ◽  
Bone Sarcoma ◽  
Particle Therapy ◽  
Phase Iii ◽  
Therapeutic Approaches ◽  
Conventional Chemotherapy ◽  
Novel Therapeutic

In patients with metastatic or unresectable soft tissue and bone sarcoma of extremities and pelvis, survival is generally poor. The aim of the current systematic review was to analyse recent publications on treatment approaches in patients with inoperable and/or metastatic sarcoma. Original articles published between 1st January 2011 and 2nd May 2020, using the search terms ‘unresectable sarcoma’, ‘inoperability AND sarcoma’, ‘inoperab* AND sarcoma’, and ‘treatment AND unresectable AND sarcoma’ in PubMed, were potentially eligible. Out of the 839 initial articles (containing 274 duplicates) obtained and 23 further articles identified by cross-reference checking, 588 were screened, of which 447 articles were removed not meeting the inclusion criteria. A further 54 articles were excluded following full-text assessment, resulting in 87 articles finally being analysed. Of the 87 articles, 38 were retrospective (43.7%), two prospective (2.3%), six phase I or I/II trials (6.9%), 22 phase II non-randomized trials (27.6%), nine phase II randomized trials (10.3%) and eight phase III randomized trials (9.2%). Besides radio/particle therapy, isolated limb perfusion and conventional chemotherapy, novel therapeutic approaches, including immune checkpoint inhibitors and tyrosine kinase inhibitors were also identified, with partially very promising effects in advanced sarcomas. Management of inoperable, advanced or metastatic sarcomas of the pelvis and extremities remains challenging, with the optimal treatment to be defined individually. Besides conventional chemotherapy, some novel therapeutic approaches have promising effects in both bone and soft tissue subtypes. Considering that only a small proportion of studies were randomized, the clinical evidence currently remains moderate and thus calls for further large, randomized clinical trials. Cite this article: EFORT Open Rev 2020;5:799-814. DOI: 10.1302/2058-5241.5.200069

scholarly journals Characteristics of COVID-19 clinical trials registered with ClinicalTrials.gov: cross-sectional analysis

BMJ Open ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. e041276 ◽  
Author(s):  
Christopher W Jones ◽  
Ashley L Woodford ◽  
Timothy F Platts-Mills
Keyword(s):  
Clinical Trials ◽  
Sequential Assignment ◽  
Open Label ◽  
Cross Sectional ◽  
Cross Sectional Analysis ◽  
Research Activities ◽  
Accurate Treatment ◽  
Completion Date ◽  
Double Blinded ◽  
Sectional Analysis

ObjectivesTo characterise current COVID-19-related research activities.DesignCross-sectional analysis.SettingClinical trials registered with ClinicalTrials.gov testing interventions relevant to COVID-19.Data sourcesClinicalTrials.gov was searched for COVID-19 and related terms to identify trials registered between 1 December 2019 and 1 May 2020 that test interventions related to the COVID-19 pandemic.Main outcome measuresWe classified trials according to intervention type, and report key trial characteristics including recruitment status, location, funder type, target enrolment number, intervention model (single group, randomised or sequential assignment) and projected completion date.ResultsOf the 630 identified clinical trials related to COVID-19, 509 (81%) involved the study of drugs or biological agents. Of these trials of drugs and biologics, 305 (60%) use an open-label design, 43 (8%) are single blinded (participant only) and 161 (32%) are double blinded (participant and investigator). 94 (18%) of the drug/biological trials are non-randomised. Either hydroxychloroquine or chloroquine is administered as part of the study protocol in 152 (30%) of the drug/biological trials. The total planned enrolment for these hydroxychloroquine/chloroquine trials is over 200 000 participants, which represents 65% of the total planned enrolment for all registered trials of drugs or biologics. There are also at least 25 registered trials of azithromycin (n=53), convalescent plasma (n=38), lopinavir/ritonavir (n=30), stem cell treatments (n=29) and tocilizumab (n=25). 142 trials were registered in the first 3 months of 2020, and 488 trials were registered between 1 April and 1 May 2020.ConclusionsThese findings demonstrate a robust research response to the COVID-19 pandemic, though many of the currently planned and ongoing trials focus on a small number of potential therapies, and many also lack essential design features and power necessary to provide accurate treatment effect estimates.

scholarly journals Novel therapeutic approaches for the management of cystic fibrosis

2020 ◽  
Vol 15 ◽  
Author(s):  
Ryan Jaques ◽  
Arslan Shakeel ◽  
Cameron Hoyle
Keyword(s):  
Cystic Fibrosis ◽  
Recurrent Infection ◽  
Current Evidence ◽  
Therapeutic Approaches ◽  
Genetic Condition ◽  
Disease Treatment ◽  
Pharmacological Agents ◽  
Ongoing Research ◽  
Mucus Clearance ◽  
Made In

Cystic fibrosis (CF) is a genetic condition characterised by the build-up of thick, sticky mucus that can damage many of the body’s organs. It is a life-long disease that results in a shortened life expectancy, often due to the progression of advanced lung disease. Treatment has previously targeted the downstream symptoms such as diminished mucus clearance and recurrent infection. More recently, significant advances have been made in treating the cause of the disease by targeting the faulty gene responsible. Hope for the development of potential therapies lies with ongoing research into new pharmacological agents and gene therapy. This review gives an overview of CF, and summarises the current evidence regarding the disease management and upcoming strategies aimed at treating or potentially curing this condition.

scholarly journals A summary of current NKG2D-based CAR clinical trials

2021 ◽  
Author(s):  
Sophie Curio ◽  
Gustav Jonsson ◽  
Sonja Marinovic ◽  
Keyword(s):  
Clinical Trials ◽  
Tumor Cells ◽  
Treatment Options ◽  
Therapeutic Approaches ◽  
Ongoing Research ◽  
New Therapeutic Approaches ◽  
Important Player ◽  
Cancer Types ◽  
Stressed Cells ◽  
Cancer Immunotherapies

Abstract Cancer immunotherapies have significantly improved patient survival and treatment options in recent years. Nonetheless, the success of immunotherapy is limited to certain cancer types and specific subgroups of patients, making the development of new therapeutic approaches a topic of ongoing research. Chimeric antigen receptor (CAR) cells are engineered immune cells that are programmed to specifically eliminate cancer cells. Ideally, a CAR recognizes antigens that are restricted to tumor cells to avoid off-target effects. NKG2D is an activating immunoreceptor and an important player in anti-tumor immunity due to its ability to recognize tumor cells and initiate an anti-tumor immune response. Ligands for NKG2D are expressed on malignant or stressed cells and typically absent from healthy tissue, making it a promising CAR candidate. Here, we provide a summary of past and ongoing NKG2D-based CAR clinical trials and comment on potential pitfalls.

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