Santiago Regiã³n Metropolitana, Chile

A Dose Range-Finding Study to Assess the Efficacy and Safety of Multiple Dose Levels of AZD8630 in Adults With Uncontrolled Asthma at Risk of Exacerbations

This is a Phase II, randomised, placebo-controlled, double-blind, dose range-finding, multi-centre study to assess the efficacy and safety of inhaled AZD8630 administered at 3 doses via an inhaler in adult patients with uncontrolled asthma, at risk of an exacerbation. The study duration up to 57 weeks for participants in the optional safety extension study and up to 17 weeks for those not included. The maximal treatment period is up to 52 weeks. This study will be conducted in approximately 220 centres in 20-25 countries. Approximately 516 patients will be randomised globally

A Phase 3 Study to Evaluate Petosemtamab Plus Pembrolizumab Vs Pembrolizumab in First-line Treatment of Head and Neck Cancer

This is a Phase 3 randomized, open-label study to evaluate the efficacy and safety of petosemtamab plus pembrolizumab vs pembrolizumab in first-line treatment of recurrent or metastatic PD-L1+ HNSCC. HNSCC patients should not have had previous systemic therapy administered in the recurrent or metastatic setting, although previous systemic therapy as part of multimodal treatment for locally advanced disease is allowed if PD was ≥6 months after the last platinum-containing therapy dose. Previous treatments with anti PD-(L)1 or anti-EGFR therapies are not allowed. In the case of cetuximab, patients who have received cetuximab with radiotherapy as a local treatment and PD was >1 year after the last dose of cetuximab are eligible.

Effectiveness And Impact Of Nirsevimab In Chile (NIRSE-CL)

The primary aim of NirseCL is to evaluate the effectiveness of nirsevimab against Respiratory Syncytial Virus (RSV) in infants during the 2024 RSV season in Chile. The secondary objective is to determine the impact on RSV-related health outcomes at a national level. The target population to receive nirsevimab is approximately 160,000 subjects, including the entire newborn cohort born during the autumn-winter season, from April 1st, 2024, to September 31st, 2024, infants born from October 1st, 2023, to March 31st, 2024, which are 6 to 1 month old at the time of immunization in April-June, and the high-risk group defined as infants born with 29 weeks of gestational age (wga) or less who were born within nine months of the beginning of the RSV season; those born with Bronchopulmonary Dysplasia (BPD), 32 or less wga and/or a birth weight less than 1·5 kgs born within one year of the beginning of the RSV season, and newborns 34 or less wga and/or weight less than 2·5 kgs born during the RSV season. Nirsevimab will be administered as part of Chile's national immunization program, following the implementation plan designed by the Ministry of Health. The coverage with nirsevimab in the target population is expected to be high (95% for those born during the winter campaign and 80% for those born before the beginning of the autumn-winter season). The primary outcome measure for effectiveness will be lower-tract respiratory infection hospitalizations (LRTI) attributed to RSV in the pediatric intensive care units (PICU) at a nationwide and regional level, and the secondary outcomes will be overall LRTI hospitalizations attributed to RSV, LRTI hospitalizations, and hospitalizations due to any cause. Additional outcomes might be included if enough statistical power is attained. Effectiveness will be determined using a two-step process. First, historical data will be used to determine the set of ICD10 diagnosis codes that are attributable to RSV infection by using data from the Chilean national sentinel program and consolidated hospitalization records. Afterward, A series of complementary statistical analyses at different aggregation levels will be conducted to estimate the impact of nirsevimab on the target population. Detailed patient-level information will be used to compare LRTI hospitalizations of those receiving the immunization against those who did not, using an adjusted proportional hazard rates regression model to estimate the effectiveness of nirsevimab as a function of covariates such as wga, weight at birth, sex, nationality, maternal education, coexisting conditions, MMR vaccination (as an indicator of access to medical care), and place of birth. This method has been used to evaluate recent nationwide vaccination campaigns in Chile (Jara et al, 2021). A case-control matching approach will be used as an alternative method intended to gain statistical efficiency (Rose and van der Laan, 2009). Finally, as a robustness analysis, a synthetic control method that allows the comparison of whole time series without relying on individual-level data will be used (Bruhn et al., 2016).

Fluid Intolerance Signals as Safety Limits to Prevent Fluid-induced Harm During Septic Shock Resuscitation

Fluids are the first-line hemodynamic therapy during septic shock resuscitation, restoring tissue perfusion by effectively increasing cardiac output and oxygen delivery. Nevertheless, resuscitation fluids can be seen as a double-edged sword since they have a narrow therapeutic index. In the one hand, insufficient fluid administration can perpetuate hypoperfusion, leading to irreversible tissue hypoxia, while excessive fluid administration can lead to fluid-induced harm. The extreme scenario of this condition, fluid overload, has been consistently associated with worse clinical outcomes, including increased risks of prolonged mechanical ventilation, acute kidney injury and mortality. As an eminently retrospective diagnosis, it may underestimate the importance of timely recognition of fluid-induced harm during the resuscitation period and could shift clinicians' efforts to treatment rather than prevention. Thus, identifying organ-specific venous congestion signals early on during the resuscitation process is desirable and could avoid these adverse outcomes. Recent studies have shown that venous congestion signals are present even during the first day of ICU admission. The investigators hypothesized that in critically ill patients with septic shock, a fluid resuscitation strategy that integrates fluid intolerance signals as safety limits will prevent fluid-induced harm, without compromising hypoperfusion resolution, compared to a standard resuscitation strategy. To confirm this hypothesis, the investigators propose a multicenter prospective randomized controlled study in 62 critically ill patients with septic shock, comparing two strategies for conducting fluid resuscitation, aiming to decrease fluid-induced harm. One strategy will follow the standard of care, while the other will rest on real-time ultrasound-based monitoring of fluid intolerance signals. The latter approach will allow clinicians to limit fluid administration when potentially deleterious signals appear. The impact of both strategies on fluid-induced harm will be assessed by the evolution of key organ function biomarkers, namely lungs, heart, and kidneys during the 6-hour study period. Perfusion dynamics will be assessed by capillary refill time and arterial lactate kinetics during the study period. Patients will receive general monitoring and management according to ICU standards. Patients will be followed-up for 28 days for other relevant outcomes.

Effect of Virtual Reality-based Therapy on Negative Symptoms in People with Schizophrenia

A Phase 2a/b Study of the Efficacy and Safety of Subcutaneous Amlitelimab in Adults With Nonresponsive Celiac Disease

Magnetic Duodeno-Ileal Chile Study

The objective of the MagDI Chile Study is to evaluate the feasibility / performance, safety, and initial efficacy of the MagDI System in eligible participants who are indicated for a duodeno-ileal (small bowel) side-to-side anastomosis procedure for partial intestinal diversion (e.g., one example of a small bowel clinical procedure requiring a side-to-side anastomosis). The partial diversion of intestinal contents from the duodenum to the ileum via side-to-side duodeno-ileostomy is intended to facilitate weight management / loss in obese adults and improve metabolic outcomes in obese adults with and without type 2 diabetes mellitus (T2DM). Side-to-side anastomoses are currently created by sutures, staples, and anastomotic compression devices. The most common side-to-side anastomosis technique used today is stapling, requiring cutting of the intestines and staples remain behind in the body. Linear staplers are available in different sizes (e.g., 30mm, 45mm, 50mm, 60mm). A predicate for this side-to-side duodeno-ileostomy diversion procedure is the single-anastomosis duodeno-ileostomy (SADI) procedure.

Safety, Tolerability, and Effectiveness of Duodenal Mucosal RF Vapor Ablation for Insulin Elimination in Type-2 Diabetes

This is a prospective, open-label pilot, to determine safety and efficacy of step-up therapy with RFVA and Semaglutide

Phase IIa Study Evaluating AZD7798 in Crohn's Disease