scholarly journals Convalescent Plasma to Limit Coronavirus Associated Complications: A Proof of Concept Phase-2 Clinical Study at a designated COVID-19 hospital in Mumbai city

2021 ◽  
Vol 4 (05) ◽  
pp. 940-949
Author(s):  
Behram Pardiwalla ◽  
Ajaykumar Yadav ◽  
Ashima Bhatia ◽  
Kedar Toraskar ◽  
Vijay Sharma ◽  
...  
Keyword(s):  
Standard Treatment ◽  
Treatment Options ◽  
Phase 2 ◽  
Proof Of Concept ◽  
Open Label ◽  
Arterial Blood ◽  
Significant Difference ◽  
Fraction Of Inspired Oxygen ◽  
Blood Fraction ◽  
Randomised Controlled

Objective: With few treatment options available to manage coronavirus disease 2019 (COVID-19), health systems devised strategies to manage covid-19 using repurposed drugs and revisiting older strategies, such as convalescent plasma. This study was planned to evaluate safety and efficacy of Anti-SARS-CoV-2 convalescent plasma in hospitalized subjects with COVID-19. Method: An open label, single centre, two arm, prospective, randomised, controlled exploratory phase 2 study was conducted at a covid-19 designated center. 20 subjects (≥18 years) were admitted to hospital (screened 15 June to 27 July 2020) with confirmed moderate covid-19 (partial pressure of oxygen in arterial blood/ fraction of inspired oxygen (PaO2/FiO2) ratio between 200 mm Hg and 300 mm Hg or a respiratory rate of more than 24/min with oxygen saturation 93% or less on room air): 10 subjects were assigned to convalescent plasma with standard treatment (test arm) and 10 subjects to standard treatment only (control arm). Subjects in the test arm received either single or two doses of convalescent plasma 24 hours apart based on their clinical condition as per investigator’s discretion. Results: Subjects in test arm showed earlier resolution of symptoms of fever, shortness of breath and cough and the mean duration for RT-PCR test turning negative was better in the test arm. One subject in the control arm progressed to severe ARDS, while none in test arm progressed to severe ARDS. There was no difference in the use of respiratory support (invasive and non-invasive ventilation) between the 2 arms. There was no mortality observed in the study and no serious adverse reaction observed with the transfusion of convalescent plasma in the study. Conclusion: This was an exploratory proof of concept study to explore the effectiveness of convalescent plasma in COVID-19 subjects and sample size was not large enough to detect a statistically significant difference however subjects in test arm of this study showed better outcomes in few of the efficacy parameters as compared to subjects in control arm. The use of convalescent plasma transfusion was also observed to be safe.

scholarly journals Evaluation of the efficacy and safety of inhaled magnesium sulphate in combination with standard treatment in patients with moderate or severe COVID-19: A structured summary of a study protocol for a randomised controlled trial

Trials ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Guitti Pourdowlat ◽  
Seyed Ruhollah Mousavinasab ◽  
Behrooz Farzanegan ◽  
Alireza Kashefizadeh ◽  
Zohreh Akhoundi Meybodi ◽  
...  
Keyword(s):  
Oxygen Saturation ◽  
Magnesium Sulphate ◽  
Standard Treatment ◽  
Controlled Trial ◽  
Arterial Oxygen Saturation ◽  
Arterial Oxygen ◽  
Open Label ◽  
Arterial Blood ◽  
Full Protocol ◽  
Randomised Controlled

Abstract Objectives Basic and clinical studies have shown that magnesium sulphate ameliorates lung injury and controls asthma attacks by anti-inflammatory and bronchodilatory effects. Both intravenous and inhaled magnesium sulphate have a clinical impact on acute severe asthma by inhibition of airway smooth muscle contraction. Besides, magnesium sulphate can dilate constricted pulmonary arteries and reduce pulmonary artery resistance. However, it may affect systemic arteries when administered intravenously. A large number of patients with covid-19 admitted to the hospital suffer from pulmonary involvement. COVID-19 can cause hypoxia due to the involvement of the respiratory airways and parenchyma along with circulatory impairment, which induce ventilation-perfusion mismatch. This condition may result in hypoxemia and low arterial blood oxygen pressure and saturation presented with some degree of dyspnoea and shortness of breath. Inhaled magnesium sulphate as a smooth muscle relaxant (natural calcium antagonist) can cause both bronchodilator and consequently vasodilator effects (via a direct effect on alveolar arterioles in well-ventilated areas) in the respiratory tract. We aim to investigate if inhaled magnesium sulphate as adjuvant therapy to standard treatment can reduce ventilation-perfusion mismatch in the respiratory tract and subsequently improve arterial oxygen saturation in hospitalized patients with COVID-19. Trial design A multi-centre, open-label, randomised controlled trial (RCT) with two parallel arms design (1:1 ratio) Participants Patients aged 18-80 years hospitalized at Masih Daneshvari Hospital and Shahid Dr. Labbafinejad hospital in Tehran and Shahid Sadoughi Hospital in Yazd will be included if they meet the inclusion criteria of the study. Inclusion criteria are defined as 1. Confirmed diagnosis of SARS-CoV-2 infection based on polymerase chain reaction (PCR) of nasopharyngeal secretions or clinical manifestations along with chest computed tomography (chest CT) scan 2. Presenting with moderate or severe COVID-19 lung involvement confirmed with chest CT scan and arterial oxygen saturation below 93% 3. Length of hospital stay ≤48 hours. Patients with underlying cardiovascular diseases including congestive heart failure, bradyarrhythmia, heart block, the myocardial injury will be excluded from the study. Intervention and comparator Participants will be randomly divided into two arms. Patients in the intervention arm will be given both standard treatment for COVID-19 (according to the national guideline) and magnesium sulphate (5 cc of a 20% injectable vial or 2 cc of a 50% injectable vial will be diluted by 50 cc distilled water and nebulized via a mask) every eight hours for five days. Patients in the control (comparator) arm will only receive standard treatment for COVID-19. Main outcomes Improvement of respiratory function and symptoms including arterial blood oxygen saturation, dyspnoea (according to NYHA functional classification), and cough within the first five days of randomization. Randomisation Block randomisation will be used to allocate eligible patients to the study arms (in a 1:1 ratio). Computer software will be applied to randomly select the blocks. Blinding (masking) The study is an open-label RCT without blinding. Numbers to be randomised (sample size) The trial will be performed on 100 patients who will be randomly divided into two arms of control (50) and intervention (50). Trial Status The protocol is Version 5.0, January 05, 2021. Recruitment of the participants started on July 30, 2020, and it is anticipated to be completed by February 28, 2021. Trial registration The trial was registered in the Iranian Registry of Clinical Trials (IRCT) on July 28, 2020. It is available on https://en.irct.ir/trial/49879. The registration number is IRCT20191211045691N1. Full protocol The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest of expediting the dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

scholarly journals Inhaled budesonide in the treatment of early COVID-19 (STOIC): a phase 2, open-label, randomised controlled trial

2021 ◽  
Author(s):  
Sanjay Ramakrishnan ◽  
Dan V Nicolau ◽  
Beverly Langford ◽  
Mahdi Mahdi ◽  
Helen Jeffers ◽  
...  
Keyword(s):  
Randomised Controlled Trial ◽  
Controlled Trial ◽  
Phase 2 ◽  
Open Label ◽  
Inhaled Budesonide ◽  
Randomised Controlled

Regorafenib compared with lomustine in patients with relapsed glioblastoma (REGOMA): a multicentre, open-label, randomised, controlled, phase 2 trial

2019 ◽  
Vol 20 (1) ◽  
pp. 110-119 ◽  
Author(s):  
Giuseppe Lombardi ◽  
Gian Luca De Salvo ◽  
Alba Ariela Brandes ◽  
Marica Eoli ◽  
Roberta Rudà ◽  
...  
Keyword(s):  
Phase 2 ◽  
Open Label ◽  
Phase 2 Trial ◽  
Randomised Controlled

scholarly journals Aspirin in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

2021 ◽  
Author(s):  
Peter W Horby ◽  
Guilherme Pessoa-Amorim ◽  
Natalie Staplin ◽  
Jonathan R Emberson ◽  
Enti Spata ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Usual Care ◽  
Rate Ratio ◽  
Invasive Mechanical Ventilation ◽  
Standard Of Care ◽  
Open Label ◽  
Absolute Increase ◽  
Significant Difference ◽  
Randomised Controlled ◽  
To Receive

Background: Aspirin has been proposed as a treatment for COVID-19 on the basis of its antithrombotic properties. Methods: In this randomised, controlled, open-label trial, several possible treatments were compared with usual care in patients hospitalised with COVID-19. Eligible and consenting adults were randomly allocated in a 1:1 ratio to either usual standard of care alone or usual standard of care plus 150mg aspirin once daily until discharge using web-based simple (unstratified) randomisation with allocation concealment. The primary outcome was 28-day mortality. The trial is registered with ISRCTN (50189673) and clinicaltrials.gov (NCT04381936). Findings: Between 01 November 2020 and 21 March 2021, 7351 patients were randomly allocated to receive aspirin and 7541 patients to receive usual care alone. Overall, 1222 (17%) patients allocated to aspirin and 1299 (17%) patients allocated to usual care died within 28 days (rate ratio 0.96; 95% confidence interval [CI] 0.89-1.04; p=0.35). Consistent results were seen in all pre-specified subgroups of patients. Patients allocated to aspirin had a slightly shorter duration of hospitalisation (median 8 days vs. 9 days) and a higher proportion were discharged from hospital alive within 28 days (75% vs. 74%; rate ratio 1.06; 95% CI 1.02-1.10; p=0.0062). Among those not on invasive mechanical ventilation at baseline, there was no significant difference in the proportion meeting the composite endpoint of invasive mechanical ventilation or death (21% vs. 22%; risk ratio 0.96; 95% CI 0.90-1.03; p=0.23). Aspirin use was associated with an absolute reduction in thrombotic events of 0.6% (SE 0.4%) and an absolute increase in clinically significant bleeding of 0.6% (SE 0.2%). Interpretation: In patients hospitalised with COVID-19, aspirin was not associated with reductions in 28-day mortality or in the risk of progressing to invasive mechanical ventilation or death but was associated with a small increase in the rate of being discharged alive.

Phase II study of cabozantinib (cabo) combined with pembrolizumab (pembro) in metastatic or recurrent gastric and gastroesophageal adenocarcinoma (GEC) to overcome resistance to checkpoint inhibitors.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. TPS253-TPS253
Author(s):  
Farshid Dayyani ◽  
Chloe Thomas ◽  
Gwendolyn Ung ◽  
Thomas H Taylor
Keyword(s):  
Checkpoint Inhibitors ◽  
Treatment Options ◽  
Objective Response ◽  
Unmet Need ◽  
Primary Objective ◽  
Phase 2 ◽  
Open Label ◽  
Secondary Resistance ◽  
Phase 2 Trial ◽  
Number Of Patients

TPS253 Background: GEC is the third leading cause of cancer mortality and the fifth most common malignancy worldwide. Fluoropyrimidine and platinum-based combinations are the most commonly used 1L treatment regimens. There are few standard treatment options after 1st line regimens. In the 3L+ GEC Keynote-059 trial, objective response rate (ORR) with Pembro was 15.5% in PD-L1(+) vs. 6.4% in PD-L1(-) tumors. While the responses were durable, the 6-months PFS (6-PFS) was only 14.1% and the median PFS was 2.0 mo. This highlights the remaining unmet need for the majority of patients who either are refractory or develop disease progression following treatment with PD-1 inhibitors in GEC. Cabo plus checkpoint inhibitors have shown clinical benefit in various cancers including hepatocellular, renal cell (RCC), urothelial and castration-resistant prostate cancers. In the CheckMate-9ER trial, Cabo+Nivolumab improved both OS and PFS vs sunitinib in 1L RCC. In patients with RCC who had progression on anti-PD1 inhibitor treatment, Cabo showed promising activity with an ORR of 33% and DCR of 79% (ESMO 2018, abstract 3793). Hypothesis: Based on preclinical and clinical observations, Cabo might contribute to overcoming primary or secondary resistance to PD-1 blockade in GEC. Methods: Prospective, open label, non-randomized phase 2 trial. Eligibility: Diagnosis of GEC, 2+ line of treatment including previous fluoropyrimidine/platinum, ECOG 0-2, adequate organ function, prior checkpoint inhibitor if tumor PD-L1 CPS≥10%. Treatment: Cabozantinib 40mg PO daily, Pembrolizumab 200 mg IV on day 1 of 21d cycle. Primary objective: Feasibility of the combination and estimate of efficacy. Primary endpoint:PFS-6. Secondary objectives: OS, ORR, adverse events. Total number of patients to be enrolled N = 27. Current enrollment (Sep 2020) N = 10. Statistics: If the PFS-6 is > 25%, the study would be regarded as positive, in which case it is planned to expand patient enrollment into a larger single arm phase 2 trial with additional sites to establish the efficacy of the regimen. Clinical trial information: NCT04164979.

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