scholarly journals Empirical Treatment Against Cytomegalovirus and Tuberculosis in HIV-Infected Infants with Severe Pneumonia: Study Protocol for a Multicenter, an Open-Label Randomized Controlled Clinical Trial

2021 ◽  
Author(s):  
Alfredo Tagarro ◽  
Cinta Moraleda ◽  
Sara Dominguez ◽  
Pui-Ying Iroh Tam ◽  
Christopher William Buck ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Severe Pneumonia ◽  
Standard Of Care ◽  
Empirical Treatment ◽  
Controlled Clinical Trial ◽  
African Countries ◽  
Clinical Trial Registry ◽  
Open Label ◽  
Secondary Endpoints ◽  
The Impact

Abstract Background Pneumonia is the primary cause of death among HIV-infected children in Africa, with mortality rates as high as 35-40% in infants hospitalized with severe pneumonia. Bacterial pathogens and Pneumocystis jirovecii are well known causes of pneumonia-related death, but other important causes such as cytomegalovirus (CMV) and tuberculosis (TB) remain under-recognized and under-treated.The immune response elicited by CMV may be associated with the risk of developing TB and TB disease progression, and CMV may accelerate disease caused both by HIV and TB. Minimally invasive autopsies confirm that CMV and TB are unrecognized causes of death in children wit HIV. CMV and TB may also co-infect the same child. The aim of this study is to compare the impact on 15-day and 1-year mortality of empirical treatment against TB and CMV plus standard of care (SoC) versus SoC in HIV-infected infants with severe pneumonia. Methods This is a Phase II-III, open-label randomized factorial (2x2) clinical trial, conducted in six African countries. The trial has four arms. Infants from 28 to 365 days of age HIV-infected and hospitalized with severe pneumonia will be randomized (1:1:1:1) to i) SoC, ii) valganciclovir iii) TB-T and iv) TB-T plus valganciclovir. The primary endpoint of the study is all-cause mortality, focusing on the short term (up to 15-days) and long-term (up to 1-year) mortality. Secondary endpoints include repeat hospitalization, duration of oxygen therapy during initial admission, severe and notable adverse events, adverse reactions, CMV and TB prevalence at enrolment, TB incidence, CMV viral load reduction, and evaluation of diagnostic tests such as GeneXpert Ultra on fecal and nasopharyngeal aspirate samples and urine TB-LAM.Discussion Given the challenges in diagnosing CMV and TB in children and results from previous autopsy studies that show high rates of poly-infection in HIV-infected infants with respiratory disease, , this study aims to evaluate a new approach including empirical treatment of CMV and TB for this patient population. The potential downsides of empirical treatment of these conditions including toxicity, and medication interactions, which will be evaluated with pharmacokinetics substudies. Trial Registration: ClinicalTrials.gov, NCT03915366, Universal Trial Number U111-1231-4736, Pan African Clinical Trial Registry PACTR201994797961340.

scholarly journals Predictive Monitoring: IMPact in Acute Care Cardiology Trial (PM-IMPACCT) - A Randomized Clinical Trial Protocol (Preprint)

2021 ◽  
Author(s):  
Jess Keim-Malpass ◽  
Sarah J Ratcliffe ◽  
Liza P Moorman ◽  
Matthew T Clark ◽  
Katy N Krahn ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Acute Care ◽  
Predictive Analytics ◽  
Healthcare Providers ◽  
Standard Of Care ◽  
Clinical Deterioration ◽  
Controlled Clinical Trial ◽  
Randomized Controlled ◽  
Icu Transfer ◽  
The Impact

BACKGROUND Patients on acute care wards who deteriorate and are emergently transferred to intensive care units have poor outcomes. Early identification of decompensating patients might allow for earlier clinical intervention and reduced morbidity and mortality. Advances in bedside continuous predictive analytics monitoring (i.e., artificial intelligence (AI)-based risk prediction) make complex data easily available to healthcare providers, and can provide early warning of potentially catastrophic clinical events. We present a dynamic, visual predictive analytics monitoring tool that integrates real-time bedside telemetric physiologic data into robust clinical models to estimate and communicate risk of imminent events. This tool, CoMET (Continuous Monitoring of Event Trajectories), has been shown in retrospective observational studies to predict clinical decompensation on the acute care ward. There is a need to more definitively study this advanced predictive analytics or AI monitoring system in a prospective, randomized controlled clinical trial. OBJECTIVE The goal of this trial is to determine the impact of an AI-based visual risk analytic, CoMET, on: (1) improving patient outcomes related to clinical deterioration, (2) response time to proactive clinical action, and (3) costs to the healthcare system. METHODS We propose a cluster randomized controlled trial (NCT04359641) to test the impact of displaying CoMET on an acute care cardiology and cardiothoracic surgery hospital floor. The number of admissions to a room undergoing cluster-randomization is estimated to be 10,424 over the 20-month study period. Cluster randomization based on bed number occurs every 2 months. The intervention cluster will have the CoMET score displayed (along with standard of care), while the usual care group receives standard of care only. RESULTS The primary outcome will be hours free from events of clinical deterioration. Hours of acute clinical events are defined as time when one or more of the following occur: emergent ICU transfer, emergent surgery prior to ICU transfer, cardiac arrest prior to ICU transfer, emergent intubation, or death. The clinical trial began randomization in January 2021. CONCLUSIONS Very few AI-based health analytics are translated from algorithm to real-world use. This study will use robust prospective, randomized controlled clinical trial methodology to assess the effectiveness of an advanced AI predictive analytics monitoring system incorporating real-time telemetric data for identifying clinical deterioration on acute care wards. This analysis will strengthen the ability of healthcare organizations to evolve as learning health systems, which apply bioinformatics data to improve patient outcomes by incorporating AI into knowledge tools that are successfully integrated into clinical practice by healthcare providers. CLINICALTRIAL Clinical trials identifier: NCT04359641

scholarly journals Ticagrelor vs Clopidogrel: the Impact of Platelet Inhibition on Cerebrovascular Microembolic Events during TAVR

2020 ◽  
Author(s):  
Michael A. Vavuranakis ◽  
Charalampos Kalantzis ◽  
Vassilis Voudris ◽  
Elias Kosmas ◽  
Konstantinos Kalogeras ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Aortic Valve ◽  
Protective Effect ◽  
Transcranial Doppler ◽  
Calcium Content ◽  
Platelet Inhibition ◽  
Controlled Clinical Trial ◽  
Open Label ◽  
Link Type ◽  
The Impact

ABSTRACTObjectivesTo evaluate the effects of ticagrelor versus clopidogrel and of platelet inhibition on the number of cerebrovascular microembolic events, in patients undergoing transcatheter aortic valve replacement (TAVR).BackgroundThe impact of the antiplatelet regimen and the extent of associated platelet inhibition on cerebrovascular microembolic events during TAVR are unknown.MethodsPatients scheduled for TAVR were randomized prior to the procedure to either aspirin and ticagrelor or to aspirin and clopidogrel. Platelet inhibition was expressed in P2Y12 Reaction Units (PRU) and percentage of inhibition. High intensity transient signals (HITS) were assessed with transcranial Doppler (TCD). Safety outcomes were recorded according to the VARC-2 definitions.ResultsAmong 90 patients randomized, six had inadequate TCD signal. The total number of procedural HITS was lower in the ticagrelor group (416.5 [324.8, 484.2]) (42 patients) than in the clopidogrel group (723.5 [471.5, 875.0]) (42 patients), p< 0.001. After adjusting for the duration of the procedure, diabetes, extra-cardiac arteriopathy, BMI, and aortic valve calcium content, patients on ticagrelor had on average 255.9 (95% CI: [-335.4, -176.4]) fewer total procedural HITS, than did patients on clopidogrel. Platelet inhibition was greater in those randomized to ticagrelor 26 [10, 74.5] PRU than in those randomized to clopidogrel 207.5 [120-236.2] PRU, p<0.001 and correlated significantly with procedural HITS (r=0.5, p<0.05). This protective effect was not associated with an increase in complications.ConclusionsTicagrelor resulted in fewer procedural HITS, compared to clopidogrel, in patients undergoing TAVR, while achieving greater platelet inhibition, without increasing the risk for complications.Clinical Trial(ClinicalTrials.gov Identifier: NCT02989558)CONDENSED ABSTRACTWe conducted a two-center, prospective, open label, randomized, controlled clinical trial to compare the efficacy of ticagrelor vs clopidogrel in preventing cerebrovascular embolic events as assessed by transcranial Doppler during TAVR.The total number of procedural HITS was lower in the ticagrelor group (416.5 [324.8, 484.2]) than in the clopidogrel group (723.5 [471.5, 875.0]), p< 0.001. Patients on ticagrelor had on average 255.9 (95% CI: [-335.4, -176.4]) fewer total procedural HITS than those on clopidogrel. This protective effect was not associated with an increase in complications.

scholarly journals Baidu Jieduan Granule in the Treatment of Coronavirus Disease-2019 (COVID-19): Study Protocol for an Open-Label Randomized Controlled Clinical Trial

2020 ◽  
Author(s):  
Wen Zhang ◽  
Qin Xie ◽  
Xiaoming Xu ◽  
Shuting Sun ◽  
Tian Fan ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Controlled Trial ◽  
Theory And Practice ◽  
Control Group ◽  
Controlled Clinical Trial ◽  
Efficacy And Safety ◽  
Clinical Trial Registry ◽  
Open Label ◽  
Randomized Controlled ◽  
Epidemic Diseases

Abstract Background: Currently, coronavirus disease-2019 (COVID-19) is continuously and rapidly circulating, resulting in serious and extensive impact on human health. Due to the absence of antiviral medicine for COVID-19 thus far, it is desperately need to develop the effective medicine. Traditional Chinese medicine (TCM) has been widely applied in the treatment of epidemic diseases in China, hoping to produce clinical efficacy and decrease the use of antibiotics and glucocorticoid. The aim of this study is to evaluate the efficacy and safety of Baidu Jieduan Granule in curing COVID-19. Methods/design: This multicenter, open-label randomized controlled trial is conducted 300 cases with COVID-19. The patients will be randomly (1:1) divided into treatment group or control group. All cases will receive standard therapy at the same time. The experiment group will receive Baidu Jieduan Granule treatment twice a day for 14 days. The outcomes are assessed at baseline and at 3, 5, 7, 14 days after treatment initiation. The primary outcome is the rate of symptom (fever, fatigue, and coughing) recovery. Adverse events will be monitored throughout the trial.Discussion: The study will provide a high-quality clinical evidence to support the efficacy and safety of Baidu Jieduan Granule in treatment of severe COVID-19, and also enrich the theory and practice of TCM in treating COVID-19. Trial registration: Chinese Clinical Trial Registry, ChiCTR2000029869. Registered on 15 February 2020

The effect of the transfemoral prosthetic socket interface designs on skeletal motion and socket comfort: A randomized clinical trial

2020 ◽  
Vol 44 (3) ◽  
pp. 145-154 ◽  
Author(s):  
Jason Kahle ◽  
Rebecca Maria Miro ◽  
Loi T Ho ◽  
Michael Porter ◽  
Derek J Lura ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Repeated Measures ◽  
Weight Bearing ◽  
Standard Of Care ◽  
Vertical Movement ◽  
Full Weight Bearing ◽  
Controlled Clinical Trial ◽  
Current Standard ◽  
Prosthetic Socket ◽  
The Impact

Background: The most crucial aspect of a prosthesis is the socket, as it will directly determine gait stability and quality. The current standard of care ischial ramus containment socket is reported to increase coronal stability through gait; however, socket discomfort is the primary complaint among prosthetic users. Objectives: The purpose of this study is to compare ischial ramus containment to alternatives in the transfemoral amputee population. All subjects were fit with three different sockets: traditional ischial ramus containment, a dynamic socket, and a sub-ischial. In this study, authors hypothesized socket skeletal motion would be equivalent across interventions. Study Design: Single-blind, repeated-measures, three-period randomized crossover clinical trial. Methods: Outcome measures were socket comfort score and skeletal motion, viewed coronally with X-ray measuring the position of the skeleton in relationship to the socket in full weight-bearing and full un-loading. Results: The mean age was 38.2 and mean Amputee Mobility Predictor score was 40. Mean vertical movement, horizontal movement, single limb prosthetic stance, mean femoral adduction in swing and stance, and median socket comfort score were not statistically different. Conclusion: The socket design did not significantly effect skeletal motion and socket comfort. All socket designs are suitable depending on the patient-centric preferences and prosthetist skill set. Clinical relevance The comfort of the standard of care transfemoral amputation socket has been widely reported as problematic. A comparison of alternative designs in a controlled clinical trial environment will assist the clinician in understanding the impact of design regarding skeletal motion and comfort. Users could benefit from alternatives applied in clinical practice.

Association of pre-existing autoimmune diseases in melanoma patients receiving immune checkpoint inhibition with improved survival and increased toxicity.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21586-e21586
Author(s):  
Nicholas Gulati ◽  
Arda Celen ◽  
Paul Johannet ◽  
Amelia Sawyers ◽  
Min Jae Kim ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Autoimmune Disease ◽  
Autoimmune Diseases ◽  
Immune Checkpoint ◽  
Standard Of Care ◽  
Controlled Clinical Trial ◽  
Checkpoint Inhibition ◽  
Immune Checkpoint Inhibition ◽  
Before And After ◽  
The Impact

e21586 Background: Immune checkpoint inhibition (ICI) improves progression-free (PFS) and overall survival (OS) for patients with metastatic melanoma (MM), but induces immune-related adverse events (irAEs). Pre-existing autoimmune disease (pre-AI) is considered a relative contraindication due to concerns of inciting autoimmune flare. We here tested the impact of pre-AI on both the survival and irAEs in MM patients treated with ICI. Methods: We examined MM patients treated with ICI who were enrolled in a clinicopathological database at NYULH with protocol-driven prospective follow up. We compiled a comprehensive list of 23 autoimmune diseases and examined the presence of these diseases prior to ICI treatment. We tested the associations between pre-AI and PFS, OS, and irAEs both in univariate and multivariate models. Results: 74/485 (15.3%) patients, who received 718 lines of ICI treatment as either standard of care or in clinical trials, had pre-AI, most commonly asthma (n=42), inflammatory bowel disease (n=9), psoriasis (n=9), rheumatoid arthritis (n=7), and eczema (n=6). In patients receiving ICI as standard of care (n=535), pre-AI was associated with irAEs (P=0.05) as well as with significantly improved PFS (P=0.024) and OS (P=0.007), controlling for patients’ sex, age, stage, ECOG status, and treatment line (1st line versus 2nd or 3rd line). However, no associations were observed between pre-AI and PFS (P=0.2) or irAEs (P=0.54) in the clinical trial group. Conclusions: Our data demonstrate the disparate impact of pre-AI on response and irAEs in standard of care versus the highly controlled clinical trial settings, and underscore the importance of examining the complex interaction between autoimmune disease before and after initiation of ICI. Our data also challenge the notion that clinicians should avoid use of ICI in pre-AI patients. More mechanistic research is needed to understand how to uncouple ICI response from toxicity.

scholarly journals Effectiveness and Safety of Niclosamaide as Add-on Therapy to the Standard of Care Measures in COVID-19 Management: Randomized controlled clinical trial

2021 ◽  
Author(s):  
Ahmed S. Abdulamir ◽  
Faiq I. Gorial ◽  
Sattar J Saaedi ◽  
Mohammed Fauzi Maulood ◽  
Hashim Ali Hashim ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Survival Rate ◽  
Viral Infections ◽  
Standard Of Care ◽  
Antiviral Effect ◽  
Control Group ◽  
Controlled Clinical Trial ◽  
Open Label ◽  
Randomized Controlled ◽  
Experimental Group

Background: COVID-19 pandemic has ignited the urge for repurposing old drugs as candidate antiviral medicines to treat novel challenges of viral infections. Niclosamide (NCS) is an anti-parasitic drug of known antiviral potential. Therefore, this study attempts to investigate the antiviral effect and safety of NCS on SARS-CoV-2 caused COVID-19 patients. Methods: Randomized controlled open label clinical trial encompassed 75 COVID-19 patients treated with standard of care plus NCS were included as experimental group and 75 COVID-19 patients treated with only standard of care therapy as control group. Each group was composed of 25 mild, 25 moderate and 25 severe patients. Survival rate, time to recovery, and side effects were the main endpoints for the assessment of the therapeutic effect and safety of NCS. Results: NCS did not enhance survival rate as three of severe COVID-19 patients in NCS and in control groups died (P>0.05). However, NCS, compared to control group, reduced the time to recovery in moderate and severe COVID-19 patients about 5 and 3 days, respectively but not in mild patients (P≤0.05). Most interestingly, NCS lowered time to recovery up to five days in patients with co-morbidities (P≤0.05) whereas only one day lowered in patients without co-morbidities (P>0.05). Conclusion: It is concluded that NCS accelerates time to recovery about 3 to 5 days in moderate to severe COVID-19 patients especially those with co-morbidities; hence, NCS is of clinical benefit for freeing hospital beds for more patients in pandemic crisis.

scholarly journals Direct antivirals working against the novel coronavirus: azithromycin (DAWn-AZITHRO), a randomized, multicenter, open-label, adaptive, proof-of-concept clinical trial of new antivirals working against SARS-CoV-2—azithromycin trial

Trials ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Iwein Gyselinck ◽  
◽  
Laurens Liesenborghs ◽  
Ewout Landeloos ◽  
Ann Belmans ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Standard Of Care ◽  
Ordinal Scale ◽  
Cytokine Signaling ◽  
Nasopharyngeal Swab ◽  
The Novel ◽  
Proof Of Concept ◽  
Open Label ◽  
Novel Coronavirus

Abstract Background The rapid emergence and the high disease burden of the novel coronavirus SARS-CoV-2 have created a medical need for readily available drugs that can decrease viral replication or blunt the hyperinflammatory state leading to severe COVID-19 disease. Azithromycin is a macrolide antibiotic, known for its immunomodulatory properties. It has shown antiviral effect specifically against SARS-CoV-2 in vitro and acts on cytokine signaling pathways that have been implicated in COVID-19. Methods DAWn-AZITHRO is a randomized, open-label, phase 2 proof-of-concept, multicenter clinical trial, evaluating the safety and efficacy of azithromycin for treating hospitalized patients with COVID-19. It is part of a series of trials testing promising interventions for COVID-19, running in parallel and grouped under the name DAWn-studies. Patients hospitalized on dedicated COVID wards are eligible for study inclusion when they are symptomatic (i.e., clinical or radiological signs) and have been diagnosed with COVID-19 within the last 72 h through PCR (nasopharyngeal swab or bronchoalveolar lavage) or chest CT scan showing typical features of COVID-19 and without alternate diagnosis. Patients are block-randomized (9 patients) with a 2:1 allocation to receive azithromycin plus standard of care versus standard of care alone. Standard of care is mostly supportive, but may comprise hydroxychloroquine, up to the treating physician’s discretion and depending on local policy and national health regulations. The treatment group receives azithromycin qd 500 mg during the first 5 consecutive days after inclusion. The trial will include 284 patients and recruits from 15 centers across Belgium. The primary outcome is time from admission (day 0) to life discharge or to sustained clinical improvement, defined as an improvement of two points on the WHO 7-category ordinal scale sustained for at least 3 days. Discussion The trial investigates the urgent and still unmet global need for drugs that may impact the disease course of COVID-19. It will either provide support or else justify the discouragement of the current widespread, uncontrolled use of azithromycin in patients with COVID-19. The analogous design of other parallel trials of the DAWN consortium will amplify the chance of identifying successful treatment strategies and allow comparison of treatment effects within an identical clinical context. Trial registration EU Clinical trials register EudraCT Nb 2020-001614-38. Registered on 22 April 2020

scholarly journals A Phase II Safety and Efficacy Study on Prognosis of Moderate Pneumonia in COVID-19 patients with Regular Intravenous Immunoglobulin Therapy

2021 ◽  
Author(s):  
Raman R S ◽  
Vijaykumar Bhagwan Barge ◽  
Anil Kumar Darivenula ◽  
Himanshu Dandu ◽  
Rakesh R Kartha ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Randomized Study ◽  
Standard Of Care ◽  
Immunoglobulin Therapy ◽  
Clinical Trial Registry ◽  
Open Label ◽  
Intravenous Immunoglobulin Therapy ◽  
Safety And Efficacy ◽  
Therapeutic Benefits ◽  
Wide Range

Abstract Background Currently, there is no specific drug for the treatment of COVID-19. Therapeutic benefits of intravenous immunoglobin (IVIG) have been demonstrated in wide range of diseases. The present study is conducted to evaluate the safety and efficacy of IVIG in the treatment of COVID-19 patients with moderate pneumonia. Methods An open-label, multicenter, comparative, randomized study was conducted on COVID-19 patients with moderate pneumonia. 100 eligible patients were randomized in 1:1 ratio either to receive IVIG + standard of care (SOC) or SOC. Results Duration of hospital stay was significantly shorter in IVIG group to that of SOC alone (7.7 Vs. 17.5 days). Duration for normalization of body temperature, oxygen saturation and mechanical ventilation were significantly shorter in IVIG compared to SOC. Percentages of patients on mechanical ventilation in two groups were not significantly different (24% Vs. 38%). Median time to RT-PCR negativity was significantly shorter with IVIG than SOC (7 Vs.18 days). There were only mild to moderate adverse events in both groups except for one patient (2%), who died in SOC. Conclusions IVIG was safe and efficacious as an adjuvant with other antiviral drugs in the treatment of COVID-19. The trial was registered under Clinical Trial Registry, India (CTRI/2020/06/026222).

Topical oxygen therapy in the treatment of diabetic foot ulcers: a multicentre, open, randomised controlled clinical trial

2021 ◽  
Vol 30 (Sup5) ◽  
pp. S7-S14
Author(s):  
Thomas E Serena ◽  
Neal M Bullock ◽  
Windy Cole ◽  
John Lantis ◽  
Lam Li ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Adverse Events ◽  
Diabetic Foot ◽  
Oxygen Therapy ◽  
Wound Closure ◽  
Foot Ulcers ◽  
Controlled Clinical Trial ◽  
Diabetic Foot Ulcers ◽  
Open Label ◽  
Number Of Patients

Objectives: Perfusion and blood oxygen levels are frequently insufficient in patients with hard-to-heal wounds due to poor circulation, vascular disruption and vasoconstriction, reducing the wound's capacity to heal. This study aimed to investigate the effect of topical oxygen on healing rates in patients with hard-to-heal diabetic foot ulcers (DFUs) (i.e., non-responsive over four weeks). Method: This multicentre, open-label, community-based randomised clinical trial compared standard care (SOC) with or without continuous topical oxygen therapy (TOT) for 12 weeks in patients with DFUs or minor amputation wounds. SOC included debridement, offloading with total contact casting (TCC) and appropriate moisture balance. Primary endpoints were the number of patients to achieve complete wound closure and percentage change in ulcer size. Secondary endpoints were pain levels and adverse events. Results: For the study, 145 patients were randomised with index ulcers graded Infectious Diseases Society of America (IDSA) 1 or 2, or Wagner 1 or 2. In the intention-to-treat analysis, 18/64 (28.1%) patients healed in the SOC group at 12 weeks compared with 36/81 (44.4%) in the SOC plus TOT group (p=0.044). There was a statistically significant reduction in wound area between the groups: SOC group mean reduction: 40% (standard deviation (SD) 72.1); SOC plus TOT group mean reduction: 70% (SD 45.5); per protocol p=0.005). There were no significant differences in changes to pain levels or adverse events. Conclusion: This study suggests that the addition of TOT to SOC facilitates wound closure in patients with hard-to-heal DFUs.

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