scholarly journals ARCADIA study protocol: a phase II, randomised, double-blind, placebo-controlled clinical trial to assess the safety and efficacy of AZD1656 in patients with diabetes hospitalised with suspected or confirmed COVID-19

BMJ Open ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. e049650
Author(s):  
Kieran McCafferty ◽  
Zoe Hollowood ◽  
Michelle Allen ◽  
Donna Lockhart ◽  
Jamie Chorlton ◽  
...  
Keyword(s):  
Laboratory Data ◽  
Ethics Committee ◽  
Ordinal Scale ◽  
Case Report Form ◽  
Double Blind ◽  
Immunological Mechanism ◽  
Double Blind Placebo ◽  
Increased Risk ◽  
Patients With Diabetes ◽  
The Uk

IntroductionCOVID-19, caused by SARS-CoV-2, remains a global pandemic that has affected more than 100 million people worldwide with over 4.8 million deaths as of October 2021. Patients with diabetes have both an increased susceptibility to SARS-CoV-2 infection, enhanced disease severity and increased risk of mortality. The challenge presented in these patients is both to improve glycaemic control—which itself may confer a survival advantage—and to help maintain or restore immunological homeostasis. The specific glucokinase activator AZD1656 may address both of these challenges via its glucose-lowering effect and its immunological mechanism of action. The aim of the Alleviation of cardioRespiratory complications in patients with COVID-19 And DIAbetes (ARCADIA) trial is to investigate this hypothesis and determine whether AZD1656 can improve clinical outcomes for these patients.Methods and analysisARCADIA is a double-blind, placebo-controlled, interventional study of AZD1656 in 150 patients with either type 1 or type 2 diabetes who have been admitted to hospital with COVID-19. Eligible, consented patients will be randomised in a 1:1 manner to receive either active drug or matched placebo tablets while they are in hospital. All patients will receive the usual and current standard of care for patients with COVID-19 in that hospital. Clinical and laboratory data will be collected and assessed at baseline and throughout their participation in the study. Data will be captured in the case report form, which will be electronically archived at the end of the trial in the trial master file. The WHO 8-point Ordinal Scale for Clinical Improvement will be used to measure clinical outcome for the primary endpoint of the trial.Ethics and disseminationEthical approval has been obtained from the East Midlands-Leicester South Ethics Committee (REC 20/EM/0198) in the UK, from the National Bioethics Committee of Medicines and Medical Devices in Bucharest, Romania, and from the Ethics Committee IKEM a TN in Prague, Czech Republic. All study-related data will be used by the sponsor in accordance with local data protection law. In the UK, all patient identifiable data will be stored on a password-protected National Health Service N3 network with full audit trail. Anonymised data will be stored in an ISO27001 certificated data warehouse.Trial registration numberEudraCT 2020-002211-21, NCT04516759.

scholarly journals Effects of probiotics in patients with diabetes mellitus type 2: study protocol for a randomized, double-blind, placebo-controlled trial

Trials ◽  
2013 ◽  
Vol 14 (1) ◽  
pp. 195 ◽  
Author(s):  
Majed S Alokail ◽  
Shaun Sabico ◽  
Yousef Al-Saleh ◽  
Nasser M Al-Daghri ◽  
Khalid M Alkharfy ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Study Protocol ◽  
Diabetes Mellitus Type 2 ◽  
Controlled Trial ◽  
Diabetes Mellitus Type ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Patients With Diabetes

scholarly journals Supplementation with a Highly Concentrated Docosahexaenoic Acid (DHA) in Non-Proliferative Diabetic Retinopathy: A 2-Year Randomized Double-Blind Placebo-Controlled Study

Antioxidants ◽  
2022 ◽  
Vol 11 (1) ◽  
pp. 116
Author(s):  
Purificación Piñas García ◽  
Francisco Javier Hernández Martínez ◽  
Núria Aznárez López ◽  
Luis Castillón Torre ◽  
Mª Eugenia Tena Sempere
Keyword(s):  
Diabetic Retinopathy ◽  
Placebo Group ◽  
Docosahexaenoic Acid ◽  
Proliferative Diabetic Retinopathy ◽  
Serum Levels ◽  
Nutritional Supplement ◽  
Controlled Study ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Patients With Diabetes

We assessed the effect of a 2-year supplementation with a highly concentrated docosahexaenoic acid (DHA) product with antioxidant activity on non-proliferative diabetic retinopathy (NPDR) in a randomized double-blind placebo-controlled study. A total of 170 patients with diabetes were randomly assigned to the DHA group (n = 83) or the placebo group (n = 87). NPDR was diagnosed using non-contact slit lamp biomicroscopy examination, and classified into mild, moderate, and severe stages. Patients in the DHA group received a high rich DHA triglyceride (1050 mg/day) nutritional supplement, and those in the placebo group received olive oil capsules. The percentages of mild NPDR increased from 61.7% at baseline to 75.7% at the end of the study in the DHA group, and from 61.9% to 73.1% in the placebo group. Moderate NPDR stages decreased from 35.1% at baseline to 18.7% at the end of the study in the DHA group, and from 36.8% to 26.0% in the placebo group. In the DHA group, there were five eyes with severe NPDR at baseline, which increased to one more at the end of the study. In the placebo group, of two eyes with severe NPDR at baseline, one eye remained at the end of the study. Changes in visual acuity were not found. There were improvements in the serum levels of HbA1c in both groups, but significant differences between the DHA and the placebo groups were not found. In this study, the use of a DHA triglyceride nutraceutical supplement for 2 years did not appear to influence the slowing of the progression of NPDR.

PAciFy Cough – A multicentre, double blind, placebo controlled, crossover trial of morphine sulfate for the treatment of PulmonAry Fibrosis Cough

2021 ◽  
Author(s):  
Zhe Wu ◽  
Winston Banya ◽  
Nazia Chaudhuri ◽  
Ira Jakupovic ◽  
Toby Maher ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Clinical Trials ◽  
Pulmonary Fibrosis ◽  
Crossover Trial ◽  
Randomised Trial ◽  
Morphine Sulfate ◽  
Double Blind ◽  
Double Blind Placebo ◽  
The Uk

Abstract Background: Idiopathic pulmonary fibrosis (IPF) is a progressive disease that leads to lung scarring, Cough is reported by 85% of patients with IPF and can be a distressing symptom with a significant impact on patients’ quality of life. There are no proven effective therapies for IPF related cough. While morphine is frequently used as a palliative agent for breathlessness in IPF, its effects on cough have never been tested. PAciFy Cough is a multicenter, double-blind, placebo-controlled, crossover trial of morphine sulfate for the treatment of cough in IPF. Methods: We will recruit 44 subjects with IPF prospectively from three interstitial lung disease units in the UK, namely the Royal Brompton Hospital, Manchester University NHS Foundation Trust (MFT) and Aintree University Hospital NHS Foundation Trust. Patients will be randomized (1:1) to either placebo twice daily or morphine sulfate 5mg twice daily for 14 days. They will then crossover after a 7 day washout period. The primary endpoint is the percent change in daytime cough frequency (coughs per hour) from baseline as assessed by objective cough monitoring at Day 14 of treatment.Discussion: This multicentre, randomised trial will assess the effect of opioids on cough counts and cough associated quality of life in IPF subjects. If proven to be an effective intervention, it represents a readily available treatment for patients.Trial registration: The study was approved by the UK Medicines and Healthcare Regulatory Agency (Ref: CTA 21268/0224/001-0001 – EUDRACT 2019-003571-19 – Protocol Number RBH2019/001) on 08 April 2020, in compliance with the European Clinical Trials Directive and the Medicines for Human Use (Clinical Trials) Regulations 2004 and its subsequent amendments. The study was provided with ethical approval by the London Brent Research Ethics Committee (Ref: 20/LO/0368) on 21 May 2020 and is registered with clinicaltrials.gov (NCT04429516) on 12 June 2020, available at https://clinicaltrials.gov/ct2/show/NCT04429516

scholarly journals Efficacy and Safety of Dalbavancin for the Treatment of Acute Bacterial Skin and Skin Structure Infection (ABSSSI) in Patients with Diabetes Mellitus

2017 ◽  
Vol 4 (suppl_1) ◽  
pp. S95-S95 ◽  
Author(s):  
Michael Nowak ◽  
Urania Rappo ◽  
Pedro L Gonzalez ◽  
Jie Chen ◽  
Jennifer S McGregor ◽  
...  
Keyword(s):  
Single Dose ◽  
Clinical Success ◽  
Signs And Symptoms ◽  
Lesion Size ◽  
Categorical Variables ◽  
Continuous Variables ◽  
Double Blind ◽  
Exact Test ◽  
Increased Risk ◽  
Patients With Diabetes

Abstract Background ABSSSIs are common in patients with diabetes and have an increased risk of complications. Dalbavancin is a long-acting lipoglycopeptide with potent activity against Gram-positive pathogens responsible for ABSSSI, including methicillin-resistant Staphylococcus aureus (MRSA), and has demonstrated activity in ABSSSI with single-dose administration. We assessed outcomes in patients with and without diabetes in a clinical trial evaluating the efficacy of dalbavancin for ABSSSI. Methods In a double-blind, phase 3 trial, adult patients with ABSSSI involving deeper soft tissue or requiring significant surgical intervention, defined as major abscess, cellulitis, and traumatic wound/surgical site infection were randomized 1:1 to dalbavancin as a single-dose (1500 mg) or as a two-dose regimen (1000 mg on Day 1 and 500 mg on Day 8). The primary endpoint was ≥20% reduction in erythema at 48–72 hours; clinical success on Days 14 and 28 was defined as improvement in lesion size and signs and symptoms. P-values were obtained using Fisher’s exact test for categorical variables and Wilcoxon rank-sum test for continuous variables. In a post-hoc subgroup analysis, outcomes were compared among the subgroups of participants with and without diabetes. Results There were 76/698 (10.9%) participants with diabetes and 622/698 (89.1%) participants without diabetes. Participants with diabetes were more likely to be older or obese, and had higher rates of cellulitis, while participants without diabetes had higher rates of abscess (Figure 1). At Days 14 and 28, clinical success was achieved in ≥84% of participants with diabetes, and investigator assessment of cure was achieved in ≥95% of participants with diabetes (Figure 2). Drug-related adverse events were observed in 7 (9.2%) patients with and 44 (7.1%) participants without diabetes. Conclusion Dalbavancin has similar rates of clinical response and success for the treatment of ABSSSI in patients with or without diabetes. Disclosures M. Nowak, Allergan plc: Employee, Salary. U. Rappo, Allergan plc: Employee and Shareholder, Salary. P. L. Gonzalez, Allergan plc: Employee and Shareholder, Salary. J. Chen, Allergan plc: Employee, Salary. J. S. McGregor, Allergan plc: Employee, Salary. J. Bryowsky, Allergan plc: Employee and Shareholder, Salary.

scholarly journals Prevention of hepatic encephalopathy by administration of rifaximin and lactulose in patients with liver cirrhosis undergoing placement of a transjugular intrahepatic portosystemic shunt (TIPS): a multicentre randomised, double blind, placebo controlled trial (PEARL trial)

2020 ◽  
Vol 7 (1) ◽  
pp. e000531
Author(s):  
K de Wit ◽  
J J Schaapman ◽  
F Nevens ◽  
J Verbeek ◽  
S Coenen ◽  
...  
Keyword(s):  
Liver Cirrhosis ◽  
Hepatic Encephalopathy ◽  
The Netherlands ◽  
Transjugular Intrahepatic Portosystemic Shunt ◽  
Controlled Trial ◽  
Ethics Committee ◽  
Portosystemic Shunt ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Intrahepatic Portosystemic Shunt

IntroductionCirrhotic patients with portal hypertension can suffer from variceal bleeding or refractory ascites and can benefit from a transjugular intrahepatic portosystemic shunt (TIPS). Post-TIPS hepatic encephalopathy (HE) is a common (20%–54%) and often severe complication. A prophylactic strategy is lacking.Methods and analysisThe Prevention of hepatic Encephalopathy by Administration of Rifaximin and Lactulose in patients with liver cirrhosis undergoing placement of a TIPS (PEARL) trial, is a multicentre randomised, double blind, placebo controlled trial. Patients undergoing covered TIPS placement are prescribed either rifaximin 550 mg two times per day and lactulose 25 mL two times per day (starting dose) or placebo 550 mg two times per day and lactulose 25 mL two times per day from 72 hours before and until 3 months after TIPS placement. Primary endpoint is the development of overt HE (OHE) within 3 months (according to West Haven criteria). Secondary endpoints include 90-day mortality; development of a second episode of OHE; time to development of episode(s) of OHE; development of minimal HE; molecular changes in peripheral and portal blood samples; quality of life and cost-effectiveness. The total sample size is 238 patients and recruitment period is 3 years in six hospitals in the Netherlands and one in Belgium.Ethics and disseminationThis study protocol was approved in the Netherlands by the Medical Research Ethics Committee of the Academic Medical Centre, Amsterdam (2018-332), in Belgium by the Ethics Committee Research UZ/KU Leuven (S62577) and competent authorities. This study will be conducted in accordance with Good Clinical Practice guidelines and the principles of the Declaration of Helsinki. Study results will be submitted for publication in a peer-reviewed journal.Trial registration numbersClinicalTrials.gov (NCT04073290) and EudraCT database (2018-004323-37).

scholarly journals The efficacy and safety of levilimab in severely ill COVID-19 patients not requiring mechanical ventilation: results of a multicenter randomized double-blind placebo-controlled phase III CORONA clinical study

2021 ◽  
Author(s):  
Nikita V. Lomakin ◽  
Bulat A. Bakirov ◽  
Denis N. Protsenko ◽  
Vadim I. Mazurov ◽  
Gaziyavdibir H. Musaev ◽  
...  
Keyword(s):  
Clinical Improvement ◽  
Rescue Therapy ◽  
Subcutaneous Administration ◽  
Phase Iii ◽  
Ordinal Scale ◽  
Primary Efficacy ◽  
Efficacy And Safety ◽  
Double Blind ◽  
Improvement Rate ◽  
Double Blind Placebo

Abstract Objective and design The aim of this double-blind, placebo-controlled, phase III CORONA clinical trial was to evaluate the efficacy and safety of IL-6 receptor inhibitor levilimab (LVL) in subjects with severe COVID-19. Subjects The study included 217 patients. The eligible were men and non-pregnant women aged 18 years or older, hospitalized for severe COVID-19 pneumonia. Treatment 206 subjects were randomized (1:1) to receive single subcutaneous administration of LVL 324 mg or placebo, both in combination with standard of care (SOC). 204 patients received allocated therapy. After the LVL/placebo administration in case of deterioration of symptoms, the investigator could perform a single open-label LVL 324 mg administration as the rescue therapy. Methods The primary efficacy endpoint was the proportion of patients with sustained clinical improvement on the 7-category ordinal scale on Day 14. All efficacy data obtained after rescue therapy administration were considered missing. For primary efficacy analysis, all subjects with missing data were considered non-responders. Results 63.1% and 42.7% of patients in the LVL and in the placebo groups, respectively, achieved sustained clinical improvement on Day 14 (P = .0017). The frequency of adverse drug reactions was comparable between the groups. Conclusion In patients with radiologically confirmed SARS-CoV-2 pneumonia, requiring or not oxygen therapy (but not ventilation) with no signs of other active infection administration of LVL + SOC results in an increase of sustained clinical improvement rate. Trail registration The trial is registered at the US National Institutes of Health (ClinicalTrials.gov; NCT04397562).

scholarly journals Amisulpride augmentation of clozapine for treatment-refractory schizophrenia: a double-blind, placebo-controlled trial

2018 ◽  
Vol 8 (7) ◽  
pp. 185-197 ◽  
Author(s):  
Thomas R.E. Barnes ◽  
Verity Leeson ◽  
Carol Paton ◽  
Louise Marston ◽  
David P. Osborn ◽  
...  
Keyword(s):  
Clinical Response ◽  
Negative Symptoms ◽  
Primary Outcome ◽  
Controlled Trial ◽  
Control Group ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Persistent Symptoms ◽  
Cardiac Symptoms ◽  
Increased Risk

Background: A second antipsychotic is commonly added to clozapine to treat refractory schizophrenia, notwithstanding the limited evidence to support such practice. Methods: The efficacy and adverse effects of this pharmacological strategy were examined in a double-blind, placebo-controlled, 12-week randomized trial of clozapine augmentation with amisulpride, involving 68 adults with treatment-resistant schizophrenia and persistent symptoms despite a predefined trial of clozapine. Results: There were no statistically significant differences between the amisulpride and placebo groups on the primary outcome measure (clinical response defined as a 20% reduction in total Positive and Negative Syndrome Scale score) or other mental state measures. However, the trial under recruited and was therefore underpowered to detect differences in the primary outcome, meaning that acceptance of the null hypothesis carries an increased risk of type II error. The findings suggested that amisulpride-treated participants were more likely to fulfil the clinical response criterion, odds ratio 1.17 (95% confidence interval 0.40–3.42) and have a greater reduction in negative symptoms, but these numerical differences were not statistically significant and only evident at 12 weeks. A significantly higher proportion of participants in the amisulpride group had at least one adverse event compared with the control group ( p = 0.014), and these were more likely to be cardiac symptoms. Conclusions: Treatment for more than 6 weeks may be required for an adequate trial of clozapine augmentation with amisulpride. The greater side-effect burden associated with this treatment strategy highlights the need for safety and tolerability monitoring, including vigilance for indicators of cardiac abnormalities, when it is used in either a clinical or research setting.

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