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NCT ID: NCT04322773 Terminated - Clinical trials for Corona Virus Disease

Anti-il6 Treatment of Serious COVID-19 Disease With Threatening Respiratory Failure

TOCIVID
Start date: April 5, 2020
Phase: Phase 2
Study type: Interventional

Coronavirus disease 2019 (COVID-19) is caused by the newly discovered coronavirus, SARS-CoV-2. The median time from onset of symptoms of COVID-19 to development of acute respiratory distress syndrome (ARDS) has been reported as short as 9 days. No effective prophylactic or post-exposure therapy is currently available. According to data from the Danish Health Authority (www.sst.dk/corona), as of March 21st, 2020, there were 1326 patients infected with the disease in Denmark, more than 250 are admitted to a hospital, and >50 of them have required intensive care. Nearly 350.000 cases and 15.000 deaths have been reported globally. These numbers are likely to markedly increase during the coming weeks, challenging the capacity of health systems worldwide. In patients infected with SARS-CoV-2, it has been described that disease severity and outcomes are related to the characteristics of the immune response. Interleukin (IL)-6 and other components of the inflammatory cascade contribute to host defense against infections. However, exaggerated synthesis of IL-6 can lead to an acute severe systemic inflammatory response known as 'cytokine storm'. In the pathogenesis of SARS-CoV-2 pneumonia, a study found that a cytokine storm involving a considerable release of proinflammatory cytokines occurred, including IL-6, IL-12, and tumor necrosis factor α (TNF-α). Studies on the Middle East respiratory syndrome caused by another coronavirus (MERS-CoV), indicate that cytokine genes of IL-6, IL-1β, and IL-8 can be markedly upregulated. Similarly, patients with SARS-CoV-2 pneumonia admitted to an intensive care unit had higher plasma levels of cytokines including IL-6, IL-2, IL-7, IL-10, granulocyte-colony stimulating factor (G-CSF), interferon-γ-inducible protein (IP10), monocyte chemoattractant protein (MCP1), macrophage inflammatory protein 1 alpha (MIP1A), and TNF-α. These findings indicate that the magnitude and characteristics of the cytokine response is related to the severity and prognosis of patients with SARS-CoV-2 pneumonia. It has been suggested that IL-6 blockade may constitute a novel therapeutic strategy for other types of cytokine storm, such as the systemic inflammatory response syndrome including sepsis, macrophage activation syndrome and hemophagocytic lymphohistiocytosis. Remarkable beneficial effects of IL-6 blockade therapy using a IL-6 receptor inhibitor has been described in patients with severe SARS-CoV-2 pneumonia in a retrospective case series from China. Currently, there are two available drugs based on human monoclonal antibodies against IL-6 receptor, tocilizumab (RoActemra, Roche) and sarilumab (Kevzara, Sanofi). IL-6 receptor inhibitors are currently licensed for several autoimmune disorders and are considered well tolerated and safe in general. The most common side effects reported are upper respiratory tract infections, headache, hypertension, and abnormal liver function tests. The most serious side effects are serious infections, complications of diverticulitis, and hypersensitivity reactions. it is hypothesized that IL-6 might play a key role in the cytokine storm associated with serious adverse outcomes in patients infected with SARS-CoV-2 pneumonia, and that blockade of IL-6 would be suitable therapeutic target for these patients. The study will investigate the effect of different types of IL-6 inhibition versus no adjuvant treatment compared to standard of care in patients with severe SARS-CoV-2 pneumonia. Primary objective: To compare the effect of either one of three IL-6 inhibitor administrations, relative to the standard of care, on time to independence from supplementary oxygen therapy, measured in days from baseline to day 28, in patients with severe SARS-CoV-2 pneumonia.

NCT ID: NCT04322396 Terminated - Clinical trials for Corona Virus Infection

Proactive Protection With Azithromycin and hydroxyChloroquine in Hospitalized Patients With COVID-19

ProPAC-COVID
Start date: April 6, 2020
Phase: Phase 2
Study type: Interventional

This study explores whether patients acutely hospitalized may have shorter hospitalization and fewer admittances at Intensive Care Units by treatment with azithromycin and hydroxychloroquine.

NCT ID: NCT04315350 Terminated - Insulin Resistance Clinical Trials

The Effect of Curcumin on the Development of Prednisolone-induced Hepatic Insulin Resistance

CURPRED
Start date: December 1, 2019
Phase: N/A
Study type: Interventional

The aim of this study is to investigate whether ingestion of curcumin will prevent hepatic insulin resistance (assessed by homeostatic model assessment of insulin resistance (HOMA-IR)) induced by short-term oral glucocorticoid (prednisolone) administration in overweight and obese participants. As a secondary endpoint it will be investigated if prednisolone administration induce or worsen the degree of NAFLD in overweight or obese participants using magnetic resonance (MR) spectroscopy (MRS), and if curcumin can ameliorate this effect. Also, the possible anti-inflammatory effect of curcumin will be elucidated as a range of inflammatory markers before and after intervention will be measured. Thus, prednisolone treatment is used as a model of development of pre-diabetes.

NCT ID: NCT04311489 Terminated - Cirrhosis, Liver Clinical Trials

Refractory Ascites in Patients With Liver Cirrhosis, and the Potential Treatment With 48 Hours Infusion of Ularitide.

ULA04
Start date: August 1, 2020
Phase: Phase 2
Study type: Interventional

This clinical trial intends to investigate the safety, tolerability and efficacy of ularitide on the renal response in patients with liver cirrhosis and refractory ascites for a maximum exposure duration of 48 hours, through a randomized, placebo-controlled, double-blind, single-center trial.

NCT ID: NCT04308395 Terminated - Clinical trials for Basal Cell Nevus Syndrome

Extension Study of Patidegib Topical Gel, 2% in Subjects With Gorlin Syndrome (Basal Cell Nevus Syndrome)

Start date: June 3, 2020
Phase: Phase 3
Study type: Interventional

This is a multicenter, open label extension study evaluating the safety of Patidegib Topical Gel, 2%, applied topically twice daily to the face of adult subjects with Gorlin syndrome.

NCT ID: NCT04280055 Terminated - Cluster Headache Clinical Trials

Prophylactic Effects of Psilocybin on Chronic Cluster Headache

EPOCH
Start date: January 21, 2020
Phase: Phase 1/Phase 2
Study type: Interventional

The purpose of this study is to investigate the prophylactic effects of psilocybin in chronic cluster headache. Subjects will receive a low dose of psilocybin during 3 sessions spaced by one week. Subjects will maintain a headache diary prior to, during, and after the administrations in order to document headache frequency, intensity and duration. Subjects will undergo a fMRI scanning before the first and after the last psilocybin session.

NCT ID: NCT04271475 Terminated - Clinical trials for Chronic Thromboembolic Pulmonary Hypertension

A Study to Evaluate Efficacy and Safety of Macitentan 75 mg in Inoperable or Persistent/Recurrent Chronic Thromboembolic Pulmonary Hypertension

MACiTEPH
Start date: July 7, 2020
Phase: Phase 3
Study type: Interventional

The purpose of the study is to evaluate the effect of macitentan 75 mg versus placebo on exercise capacity at Week 28 in participants with chronic thromboembolic pulmonary hypertension (CTEPH).

NCT ID: NCT04258150 Terminated - Pancreatic Cancer Clinical Trials

Ipilimumab, Nivolumab, Tocilizumab and Radiation in Pretreated Patients With Advanced Pancreatic Cancer

TRIPPLE-R
Start date: April 16, 2020
Phase: Phase 2
Study type: Interventional

Pancreatic cancer (PC) remains a dreadful disease due to its often advanced stage at diagnosis and poor sensitivity to chemotherapy. Progression after 1. line chemotherapy is inevitable in patients with advanced PC, and treatment options for patients who progress after 1. line chemotherapy are limited. Considering the emerging role of the tumor microenvironment (TME), the combination of checkpoint blocking antibodies with agents that target the inhibitory effects of the TME could lead to better responses in tumor historically resistant to checkpoint blocking antibody approaches. Inflammation is one of the hallmarks of cancer, and contributes to PC initiation, enhanced invasiveness and metastasis. The immune-modulating cytokine interleukin-6 (IL-6) facilitates the inflammation cascade and key pathways within the respective TME, among others promotion of tumor-induced immunosuppression and facilitation of metastasis. Thus, IL-6 inhibition approach can potentially directly affect the immunosuppressive TME compartment. To explore the synergy of the proposed combinatorial approach, participants with locally advanced/metastatic pancreatic tumors who have progressed during or after at least 1 line of systemic chemotherapy in the metastatic setting will receive nivolumab and ipilimumab administered in combination with radiotherapy and tocilizumab. It is anticipated that this clinical study will inform the use of this 3-drug combination for further phase II and/or phase III clinical testing.

NCT ID: NCT04252703 Terminated - Clinical trials for Cardiovascular Diseases

'MInimalist' or 'MOre Complete' Strategies for Revascularization in Octogenarians

Start date: May 13, 2020
Phase: N/A
Study type: Interventional

Older patients with co-morbidity are increasingly represented in interventional cardiology practice. They have been historically excluded from studies regarding the optimal management of NSTEACS. Though there are associated risks with invasive treatment, such patients likely derive the greatest absolute benefit from PCI. Small, though highly selective, studies suggest a routine invasive strategy may reduce the risk of recurrent myocardial infarction. The study aims to include, as far as possible, an 'all-comers' population of patients aged 80 and above to define the optimum amount of revascularization required to achieve good outcomes and satisfactory symptom relief for this challenging cohort of patients.

NCT ID: NCT04248465 Terminated - Clinical trials for Amyotrophic Lateral Sclerosis

An Efficacy and Safety Study of Ravulizumab in ALS Participants

Start date: March 30, 2020
Phase: Phase 3
Study type: Interventional

The purpose of the study is to assess the efficacy and safety of ravulizumab for the treatment of adult participants with ALS.