Triple vs High Dose Inhaled CORticosteroids
It remains to be clarified whether triple therapy is better than high dose inhaled corticosteroids and long-acting beta2-agonists combination (ICS/LABA) in patients with uncontrolled asthma despite the use of medium dose ICS/LABA combinations, particularly in cases with high T2 biomarkers´ values. The aim of this study is to evaluate, in a real-world setting, which is the best therapeutic strategy in this clinical scenario. This study will be a randomized, open-label, two-arm, prospective, 12-month trial to be conducted in 53 hospital asthma units. Participants will be allocated to receive one of two therapeutic strategies: same ICS/LABA combination at highest doses or the same maintenance therapy plus a long-acting anticholinergic (LAMA). Follow up visits will be scheduled at 12-16, 24-28 and 52 weeks after the baseline visit. The investigators can optimise therapy according to their clinical opinion if the patient remains uncontrolled. Demographic, clinical and lung function information will be collected at each visit. The primary endpoint will be the percentage of patients controlled at week 52, with both an ACT score of 20 or greater and no severe exacerbations). 620 patients (282 patients per treatment group, considering 10% drop-out) will be required for the study to have 80% power to detect non-inferiority limit of 10% in the rate of controlled patients between the high dose ICS/LABA arm and the triple therapy arm. All effectiveness analyses will be done according to the intention-to-treat principle. Secondary endpoints: percentage of patients controlled at week 24, ACT at weeks 12, 24 and 52, AIRQ at weeks 12, 24 and 52, quality of life (Mini-AQLQ) at weeks 12, 24 and 52, postbronchodilator FEV1 at weeks 12, 24 and 52, severe exacerbations at week 24 and 52. Differences between groups in 8 AM serum cortisol at week 52. Adherence at week 52 in the two study arms. Factors related to triple and high-dose ICS/LABA failure and success (control) at week 52. The results of this study will help physicians to decide the most appropriate therapeutic strategy for a large number of asthma patients: those who do not gain control with medium dose ICS/LABA. If non-inferiority of triple therapy vs high dose ICS/LABA is demonstrated, it could lead to a modification of the current guidelines.
Phase
4Span
70 weeksSponsor
Galaxia EmpíricaSagunto, Valencia
Recruiting
Evaluation of the Effect of FertyBiotic Pregnancy in the Metabolic Profile in Pregnant Women
After being informed about the study, all patients meeting the inclusion/exclusion criteria and giving written informed consent will be randomized in a double-blind manner in a ratio 1:1 to receive the food supplementation associated with probiotics or placebo (folic acid) once daily.
Phase
N/ASpan
125 weeksSponsor
FertypharmSagunto, Valencia
Recruiting
Healthy Volunteers
A Study of Vedolizumab in Children and Teenagers With Moderate to Severe Crohn's Disease (CD)
The drug being tested in this study is called vedolizumab. Vedolizumab is being tested to treat pediatric participants who have moderately to severely active CD. The drug is tested and approved in adults in approximately 70 countries. Participants to be enrolled must have failed response to, lost response to, or been intolerant to at least 1 of the current standard of care (SOC) induction and maintenance therapies for CD including exclusive and/or partial enteral nutrition therapy, immunomodulators (e.g., azathioprine [AZA], 6-mercaptopurine [6-MP], methotrexate [MTX]), and tumor necrosis factor-alpha (TNF-α) antagonists. The study will enroll approximately 120 patients. During the Induction Period participants will receive 3 doses of vedolizumab IV infusion at Day 1, Week 2, and Week 6 based on their weight at Baseline as: - Participants 10 to 15 kg, Vedolizumab 150 mg - Participants >15 to <30 kg, Vedolizumab 200 mg - Participants ≥30 kg, Vedolizumab 300 mg At Week 14, participants who achieve clinical response will be randomly assigned (by chance, like flipping a coin) in a 1:1 ratio to one of the 2 double-blind dose groups (high dose and low dose), stratified by previous exposure/failure to TNF-α antagonists therapy or naive to TNF-α antagonists therapy, and by weight groups. Participants will receive vedolizumab IV infusions every 8 weeks (Q8W) up to Week 46 during the Maintenance Period as follows: - Participants ≥30 kg, Vedolizumab 300 mg (High dose) or 150 mg (Low dose) - Participants >15 to <30 kg, Vedolizumab 200 mg (High dose) 100 mg (Low dose) - Participants 10 to 15 kg, Vedolizumab 150 mg (High dose) or 100 mg (Low dose) The dose will remain blinded to the participant and study doctor during the study (unless there is an urgent medical need). All participants will be administered vedolizumab via IV infusion. In participants who demonstrate lack of maintenance of clinical response during the Maintenance Period the dose will be escalated in a blinded fashion to the high dose in their weight group based on the weight at the time of the worsening of disease. In addition one-time rescue therapy with corticosteroids is allowed during Maintenance Period. This multi-center trial will be conducted worldwide. After the Week 54, participants may be eligible to continue receiving vedolizumab in extension study MLN0002-3029. Participants who do not maintain corticosteroid-free clinical response at week 54 will undergo an end-of-study (EOS) or ET visit, and a safety visit 18 weeks after the last dose of vedolizumab followed by 2 years of long term follow-up (up to 104 weeks), in addition these participants will then be eligible to enter study MLN0002-3029 for an observational LTFU period of 2 years after the last dose of study drug.
Phase
3Span
212 weeksSponsor
TakedaSagunto, Valencia
Recruiting
Changes in Viral Load in COVID-19 After Probiotics
1. Study hypothesis: Through the administration of specific probiotics, the immune response against the coronavirus COVID-19 could be stimulated, being able to decrease its viral load and secondary symptomatology. There is a different way to attack a harmful microorganism. It is based on the existence in its habitat of a whole complex network of other microorganisms, our microbiota, which prevents the development, growth and feeding of that microorganism, either by competition of space, food, or immune effects. In COVID-19 patients, intestinal dysbiosis has been described, specifically observing the decrease of species considered as probiotics of the genera Lactobacillus and Bifidobacterium. The current study proposes the testing of the novel nutritional supplement to potential the patient's immune system and balances the damaged microbiota. This product contains species from the genera described as affected in the COVID-19 infection. Moreover, the strains selected showed an anti-inflammatory and antioxidant effect, and capacity for stimulation of the immune system in previous assays. All three strains have the GRAS status recognized by the FDA and are on the EFSA QPS list. The product also contains vitamin D, zinc and selenium, three powerful inducers of the immune response. It is a safe product according to WHO criteria. In addition, it can be effective despite the administration of antibiotics, due to postbiotic activity, reducing the risk of sepsis described in this type of patient. In order to monitor the effects of treatment with the functional product, a follow-up will be made by means of consultation regarding the evolution of the patient's condition. On the other hand, we will try to correlate this state with the viral load present in serum and pharyngeal-nasal scraping. 2. PRIMARY AND SECONDARY OBJECTIVES Main objective: The main objective of the study is to evaluate the capacity of the novel nutritional supplement (immune system enhancer, antioxidant and anti-inflammatory capacity) to decrease the viral load by nasopharyngeal smear in patients admitted for COVID-19 coronavirus disease. The Patient will follow the medication agreed by the Hospital committee during all the process. Secondary objectives: Monitoring of changes, in patients admitted by COVID-19+, of the following parameters at admission and prior to discharge: - Hospital stay (days). Stay in Intensive Care Unit (days) - Clinical indicators: Respiratory rate, body temperature, number of bowel movements and consistency. Abdominal pain. Nausea and vomiting. Sat02. - Type of respiratory support on day 5 of admission: ambient air (none), nasal mask, ventimask, reservoir, non-invasive mechanical ventilation (NIV), orotracheal intubation. - Analytical parameters at admission and discharge: Total lymphocytes, Hemoglobin, Ferritin, Neutrophils, Urea/Creatinine, C-reactive protein, LDH, D-dimer, AST/ALT, Platelets. - Determination of the incidence of mortality in the patient cohort and comparison with that described in the literature. 3. PRIMARY AND SECONDARY STUDY VARIABLES 3. 1. Primary study variable - Viral load during the period of admission to the nasopharyngeal smear. 3. 2. Secondary study variables - Hospital stay (days). Stay in Intensive Care Unit (days). - Clinical indicators on admission and every 48 hours thereafter: Respiratory rate, oxygen saturation, body temperature, number of bowel movements and consistency. Abdominal pain. Nausea and vomiting. - Type of respiratory support on the 5th day of admission: ambient air (none), nasal glasses, ventimask, reservoir, non-invasive mechanical ventilation (NIV), orotracheal intubation. - Mortality. - Analytical parameters at day 0 and at hospital discharge: Total lymphocytes, ferritin, hemoglobin, neutrophils, urea/creatinine, C-reactive protein, IL-6, LDH, D-dimer, AST/ALT, platelets - Appearance of side effects. 4. MATERIAL AND METHODS 4.1. Study design Randomized clinical trial with a clinical intervention of prescription of functional novel nutritional supplement. The expected duration is 3 months in all patients presenting symptoms of infection by COVID-19 or COVID+. Serum viral load will be analyzed by rt-qPCR (reverse transcriptase quantitative Polymerase Chain Reaction) at the beginning of the patient's admission and every 48 hours until remission of the infection and pharyngeal-nasal exudate. The patient medicated according to hospital protocol will also be given a daily dose (one sachet) until remission of the illness or for one month. 4.2. Sample size of the study According to GRANMO Sample Size Calculator (Version 7.12 April 2012) Accepting an alpha risk of 0.15 and a beta risk of 0.3 in a bilateral contrast, 48 subjects in the first group and 48 in the second are required to detect the difference between two proportions as statistically significant, than for group 1 (intervention group) it is expected to be 0.5 and group 2 0.7. A follow-up loss rate of 5% has been estimated. The ARCOSENE approach has been used. 4.3. Statistical plan Quantitative variables will be expressed as mean and standard deviation assuming normal distribution based on the central limit theorem. Qualitative variables will be expressed as frequencies with their 95% confidence intervals. Qualitative variables will be compared using the Chi-square test. Quantitative variables will be compared using the Student T test. In order to evaluate the impact of the intervention on the evolution of the disease by COVID-19, on average stay, clinical variables and qualitative and quantitative analyses, a multivariate analysis will be carried out, in which it will be controlled by different variables that could act as factors of confusion (age, sex, type of disease, severity of the disease on admission, other diseases that could affect the evolution, medical treatment, previous surgeries, etc.) 4.4. Planning the physical-sample drawing Main evaluation criteria: These patients will have their surgery performed pharyngeal-nasal smear on day 0 and day 5 of hospital admission. Viral load testing and cytokines: In the samples, the viral load will be determined by rt-qPCR, in hospital services. Cytokines shall be measured at the indication of the physician when deemed appropriate. 5. ETHICAL ASPECTS TAKEN INTO ACCOUNT IN THE STUDY PROTOCOL 5.1 Ethical conduct of the study The study will be carried out in accordance with the following guidelines: - Local ethical standards. - European directives on the protection of human subjects in research. - Declaration of Helsinki. - The study will be conducted in strict accordance with the international ethical recommendations for human research and clinical trials set out in the Declaration of Helsinki, and in accordance with the recommendations of the Ministry of Health on clinical trials. - Recommendations of the European Network of Pharmacoepidemiology and Pharmacovigilance Centres - GMP recommendations. - Other relevant guidelines, laws or regulations applicable in each country and in the Valencian Community As it is a research project with a nutritional supplement, it is not considered a medicine or a health product, and therefore the Biomedical Research Law applies to it and not the EECC RD 1090/2015. Therefore, there is no need for authorization by the AEMPS (State Agency for Medicines) or by the Conselleria de Sanitat. The study protocol will be submitted for prior approval to the Hospital de Sagunto IRB.
Phase
N/ASpan
48 weeksSponsor
Hospital de SaguntoSagunto, Valencia
Recruiting
A Prospective Registry Study in Patients With Unresectable Locally Advanced or Metastatic Breast Cancer (MBC)
The target population for inclusion in this study is breast cancer patients recently diagnosed (from January 2016) with unresectable locally advanced or metastatic disease (either after a recurrence or as first diagnosis). No treatment regimen will be protocol specified. This is an observational study in which clinical decisions concerning the optimum management strategy for a particular patient are taken independently of and/or prior to, any decision by the physician to invite a patient to participate in the study. The treating physician will make all treatment decisions according to his/her regular clinical practice independent of this study. Patients enrolled on the study are free to withdraw their informed consent for the use and disclosure of health information at any time and when asked, patients are not obliged to provide a reason. Patients may request discontinuation from the study at any time. The date and the reason for withdrawal or discontinuation from the study must be recorded in the electronic case report form (eCRF). An attempt will be made to determine the date of discontinuation and final status (i. e. withdrawal of consent, loss to follow-up, death) of any patient who discontinues from the study. However, the treating clinician is encouraged to follow the patient as long as possible, until patient death or through study end. The Sponsor has the right to terminate the study at any time. The Sponsor will notify the investigator if the study is placed on hold or if the Sponsor decides to discontinue the study.
Phase
N/ASpan
518 weeksSponsor
Spanish Breast Cancer Research GroupSagunto, Valencia
Recruiting