Poa, Brazil

Effects of Topical Insulin on Corneal Epithelium Healing After Corneal Crosslinking in Patients With Keratoconus

Patients from the Keratoconus Clinic at the Hospital das Clínicas of UNICAMP diagnosed with keratoconus who are indicated for crosslinking will be evaluated regarding visual acuity, refraction, biomicroscopy, automated keratometry (Auto Kerato Refractometer KR 8000® Alcon), Goldmann applanation tonometry, corneal specular microscopy (EM-3000® Tomey) for endothelial cell count, corneal tomography (Pentacam® HR 70900 Oculus), and corneal optical coherence tomography (SPECTRALIS® Heidelberg Engineering). Once indicated for crosslinking, participants will be informed by the assistants of the Keratoconus Clinic about the study. Those who, after being informed about all aspects of the crosslinking procedure and the study, and sign the Informed Consent Form, will be randomly divided into two groups of equal size and stratified by gender. Group A will receive a prescription for insulin eye drops at a concentration of 50 IU/ml in a 0.5% methylcellulose vehicle, 1 drop four times a day, until complete corneal epithelial healing. Group B will receive a prescription for 0.5% methylcellulose eye drops (placebo), 1 drop four times a day, until complete corneal epithelial healing. The corneal crosslinking will be performed according to the standardized protocol of the UNICAMP Ophthalmology Department by third-year residents, supervised by attending physicians and faculty members. The procedure will be carried out in an outpatient setting. The anesthetic technique is topical, achieved through the application of 0.4% benoxinate hydrochloride eye drops (Oxinest). A blepharostat is then placed, and 30% alcohol is applied to the corneal epithelium for 20 seconds, demarcated by an 8.0mm optical zone marker to prevent alcohol leakage. The alcohol is removed using an absorbent sponge (Merocel®), followed by thorough cleaning of the ocular surface with 0.9% sodium chloride solution. Next, the corneal epithelium in the 8.0mm region is removed using a corneal scraper, and the soaking procedure begins, consisting of the instillation of 1 drop of 0.1% riboflavin for 30 minutes at 3-minute intervals. After soaking, the cornea is exposed to UV-A radiation at 9 mW/cm² for 10 minutes, with riboflavin instilled every 2 minutes during this period. Once the procedure is completed, 1 drop of moxifloxacin hydrochloride 5.45mg/ml (Oftalmox®; Gbio) antibiotic eye drops is applied, and a silicone-hydrogel soft contact lens, Air Optix Plus Hydraglyde (Alcon), is placed. Insulin eye drops 50 IU/ml (Eye Pharma) in Group A and placebo eye drops of 0.5% methylcellulose (Eye Pharma) in Group B will be prescribed every 6 hours to the eye that underwent the crosslinking procedure until complete corneal epithelialization occurs. Both the insulin and methylcellulose eye drops will come in identical bottles, making it impossible for the participants and the research team conducting the subsequent evaluations to distinguish between them. In addition to these medications, both groups will undergo postoperative treatment with prednisolone acetate 10mg/ml (Ster®; Genom) 1 drop every 6 hours, moxifloxacin hydrochloride 5.45mg/ml (Oftalmox®; Gbio) 1 drop every 6 hours, sodium hyaluronate 0.15% (Hyabak®; Genom) 1 drop every 4 hours, and silicone-hydrogel contact lenses (Air Optix Plus Hydraglyde; Alcon). These treatments are part of the standard postoperative care prescribed by the UNICAMP Department of Ophthalmology. The primary outcome is the time to complete corneal epithelial healing. After epithelial healing, the silicone-hydrogel contact lens will be removed, and the antibiotic eye drop (Oftalmox®; Gbio) will be discontinued in both groups, as well as the insulin eye drop in Group A and the methylcellulose eye drop in Group B. At this point, both groups will be prescribed sodium hyaluronate 0.15% and prednisolone acetate 10mg/ml. Sodium hyaluronate, an ocular lubricant, will be continued until the 30th postoperative day, and prednisolone acetate will be tapered every 7 days following this schedule: every 8 hours; every 12 hours; every 24 hours; and discontinuation. Third-year residents performing the procedures will not be masked, but they will not conduct postoperative follow-up and evaluation, which will be the responsibility of the research team. Participants will be masked, and the research team conducting the follow-up will also be masked. In case of any suspected complications related to the crosslinking procedure, an independent ophthalmologist from the cornea service will evaluate the patient without knowing to which group the patient belongs and will recommend the most appropriate treatment. Postoperative visits will take place on the 1st, 2nd, and 3rd days after the crosslinking procedure. A fourth evaluation will occur on the 6th day post-procedure, with follow-ups every 48 hours until the corneal epithelium is fully healed. Typically, this period is not expected to exceed one week in either group. Subsequent follow-ups will occur on the 30th and 60th days post-procedure. This follow-up schedule is routinely performed by the UNICAMP Department of Ophthalmology. At the 1st, 2nd, 3rd, and 6th postoperative days, the researcher responsible will document corneal status through photographs obtained using the Keratograph - OCULUS® device. If complete corneal healing has not occurred by the 6th day and further visits are needed, this documentation will also be performed. During these visits, objective factors such as ocular hyperemia and the extent of the epithelial defect will be assessed. For quantitative assessment of the epithelial defect, the photographs obtained using the Keratograph - OCULUS® will be analyzed using the ImageJ software (https://imagej.nih.gov/ij/). These visits will be carried out during the patient's routine care, lasting around 30 minutes. On the 30th postoperative day, biomicroscopy and applanation tonometry will be performed, with a duration of approximately 15 minutes. On the 60th postoperative day, visual acuity, refraction, biomicroscopy, corneal tomography, corneal optical coherence tomography, and endothelial cell count will be performed, with the visit lasting around 45 minutes. After this last visit, the patient will be referred back to the Keratoconus Clinic for standard follow-up, with decisions to be made by the UNICAMP Department of Ophthalmology.

Study of Bepirovirsen in Participants Living With Human Immunodeficiency Virus and Chronic Hepatitis B Virus Infection (B-Focus)

Study to Evaluate the Effect of Balcinrenone/Dapagliflozin in Patients With Heart Failure and Impaired Kidney Function

The purpose of this study is to investigate the effect of balcinrenone/dapagliflozin compared with dapagliflozin, on the risk of CV death, HF event with and without hospitalisation, in patients with chronic HF, impaired kidney function, and who have had a recent HF event. Eligible patients will randomly be assigned with a 1:1:1 ratio to receive once daily administration of one capsule and one tablet of one of the following treatments: 1. Balcinrenone/dapagliflozin 15 mg/10 mg capsule and matching placebo for dapagliflozin 10 mg tablet 2. Balcinrenone/dapagliflozin 40 mg/10 mg capsule and matching placebo for dapagliflozin 10 mg tablet 3. Dapagliflozin 10 mg tablet and matching placebo for balcinrenone/dapagliflozin capsule The study is event driven, and the average study duration for a participant is estimated to be 22 months including screening period, 20 months blinded treatment period and a one-month follow-up period on open-label dapagliflozin. The study will be conducted at approximately 700 sites in approximately 40 countries globally.

Classifying for HER2 Dependence to De-Escalate Neoadjuvant Chemotherapy in Patients With HER2+ Early Breast Cancer Undergoing HER2 Double-Blockade

This is a nonrandomized phase II single arm study to assess de-escalation of chemotherapy in participants with HER2-positive early breast cancer undergoing neoadjuvant therapy with PHESGO™. Participants will be evaluated by central laboratory review for confirmation of selected biomarkers (pre-screening). Participants who meet the biomarker assessment criteria will follow the eligibility criteria assessment. Participants with HER2 positive disease that meet the eligibility criteria will be treated with neoadjuvant PHESGO™. A baseline PET/CT will be performed prior to start of PHESGO™ treatment. All participants will receive fixed-dose subcutaneous formulation with pertuzumab and trastuzumab (PHESGO™) every 21 days for 3 cycles to evaluate PET/CT response. After the 3rd cycle, participants achieving PET/CT response (defined in this trial as ≥40% reduction in the SUVMax as calculated by the formula SUVbaseline SUVresponse/SUVbaseline) will continue treatment with PHESGO™ for 5 additional cycles, completing 8 neoadjuvant cycles of PHESGO™. Participants without PET/CT response after 3rd cycle will be out of study and will receive treatment and surgery according to institutional standard of care. For this cohort of participant, data regarding treatment received, pCR status and outcomes will be collected. Definitive breast cancer surgery will be performed after the 8th cycle of therapy. After surgery, participants will receive adjuvant treatment according to their response. Participants achieving pCR will receive PHESGO™ alone as adjuvant treatment to complete a total of one year of therapy, thus receiving 10 cycles of adjuvant PHESGO™. Participants not achieving pCR will receive one of two adjuvant therapy options as per investigator's choice: (1) 14 cycles of trastuzumab emtansine (T-DM1), or (2) investigator's choice chemotherapy regimen (up to 6 cycles) plus 10 cycles of PHESGO™. Disease status and survival data collection will be abstracted from medical records for up to 5 years after surgery. Participants will be followed for recurrence and survival data with abstraction of data from medical records every 3 months in first year after surgery; every 4 months in second and third years; and then annually until five years. Medical procedures and therapies in the follow-up period are not a formal investigational part of this clinical trial and therefore will be performed according to the institutional standard of care.

Candesartan Cilexetil + Chlorthalidone + Amlodipine Versus Exforge HCT®️ for Systemic Arterial Hypertension

This phase III, multicenter, randomized, double-blind, controlled, parallel trial will evaluate the non-inferiority of the association between candesartan cilexetil 16mg + chlorthalidone 12.5mg + amlodipine 5mg in relation to Exforge HCT® (valsartan 160mg + hydrochlorothiazide 12 5mg + amlodipine 5mg) in the treatment of systemic arterial hypertension. A total of 698 participants will be included. Follow-up visits will occur four, eight, and twelve weeks after the date of the randomization visit. A telephone contact will be performed 30 days after the end of treatment. The primary efficacy outcome is the mean change in blood pressure, measured at the research site, 12 weeks after starting treatment, compared to baseline. Incidence of adverse events will be collected from the first dose of treatment up to 30 days after the end of the treatment foreseen in the protocol.

Study to evaLuate the effIcacy and Safety of abeLacimab in High-risk Patients With Atrial Fibrillation Who Have Been Deemed Unsuitable for Oral antiCoagulation (LILAC-TIMI 76)

Development of Online Store for Testing Regulatory Food and Nutrition Policies in Brazil

Among noncommunicable disease, cardiovascular-related diseases are the leading cause of death worldwide and contribute to almost one-third of deaths in Brazil. Cardiovascular disease has become the leading cause of death in Brazil since 1960 due in part to poor eating habits, obesity, and insufficient physical activity. Consumption of high levels of sodium, added sugar, and saturated fat is a major driver of the development of cardiovascular disease. In this context, nutrition policies and interventions, such as the use of warning labels, are an important tool for reducing risk of diet-related diseases. The Brazilian Ministry of Health has recently announced efforts to combat the country's growing burden of diet-related noncommunicable diseases, and Brazil's National Health Surveillance Agency (ANVISA) has approved a more transparent and accessible system for communicating nutrition information for foods and beverages. The proposal will require labeling with a magnifying glass symbol on the front of products' packages to inform consumers about excess nutrients (i.e., sodium, sugar, saturated fat). Similar interventions have been implemented across Latin America, including Chile, Peru, and Mexico. A recent study in Chile demonstrated a reduction in purchases of food and drink items displaying warning labels. This study seeks to test the effectiveness of different nutrient profiles to determine which products should carry the new labels in Brazil (i.e., the Pan-American Health Organization's profile or Brazil's National Health Surveillance Agency's proposed profile). Additionally, it seeks to assess whether the inclusion of information about products' ultra-processed nature further impacts consumers' product perceptions. The study will provide critical information for the Brazilian Ministry of Health on the effectiveness of the new label proposal and on strategies to inform Brazilians of product healthfulness. Participants will be initially redirected from Cint (an online panel company). Following online consent and completion of a screening survey, participants will be redirected to an experimental online grocery store (Saruê), given a shopping list, and asked to shop for the items on the list as if in a real store. Upon redirection from Cint, participants will be randomly assigned into three arms: 1) control (no FOPLs); 2) FOPLs applied to products based on Brazil's National Health Surveillance Agency (ANVISA)'s nutrient profile model; or 3) front-of-package labels applied to products based on the Pan-American Health Organization (PAHO)'s nutrient profile model. After participants select products and check out, they will answer a survey about their perceptions about the labels and products carrying them. These questions will include self-reported responses to the content (e.g., elaboration, beliefs). After data collection, data on participants' selected products in the online grocery store will be analyzed to determine which nutrient profile was the most effective in decreasing participants' consumption of key nutrients. Setting: The trial will take place in Saruê, an experimental online grocery store created for researchers to examine how front-of-package labels influence consumer purchases in a controlled but realistic environment. The online store reflects real-world prices and is modeled after Pão de Açúcar, a Brazilian online grocery store . Recruitment: Participants will be recruited through Cint, a survey research firm. The eligibility criteria are residing in Brazil, being 18 years or older, and being responsible for at least half of the grocery shopping for one's household. Participants are ineligible if they were involved in any pre-testing related to the survey. Experiments conducted using online convenience samples, such as those recruited by Cint, largely replicate findings from studies conducted via probability-based samples. Cint will screen for eligibility and recruit participants from their pool of 8 million participants in Brazil. Approximately 3,000 participants will be recruited. As compensation, participants will receive incentives or points that can be redeemed for gift cards or goods per Cint's protocols. Informed Consent: Participants will sign an informed consent form that follows a structure that is customary in Brazil. Randomization: After the participant has signed the consent form, they will be randomly assigned to one of the three study arms. Randomization order will be determined a priori. Participants will have an equal chance of being randomized to each trial arm.

Efficacy and Safety of Trimodulin (BT588) in Subjects With Severe Community-acquired Pneumonia (sCAP)

This is a randomized, placebo-controlled, double-blind, multi-center, multi-national, phase III trial, to assess the efficacy and safety of trimodulin compared to placebo treatment, as adjunctive treatment to SoC in adult hospitalized subjects with sCAP receiving IMV. Subjects will be randomized on a 1:1 basis to receive trimodulin or placebo, stratified by center. Investigational medicinal product (IMP) treatments will be blinded. Subject will be administered IMP once daily on 5 consecutive days (day 1 through day 5) adjunctive to SoC. The subsequent follow-up phase comprises maximally 23 days (day 6 through day 28) followed by an end-of-follow-up visit/telephone call on day 29 [+3]. For subjects still in the hospital (trial site) after day 29, an extended follow-up is conducted until discharge or until day 90. For all subjects alive on day 29, a closing visit/telephone call on day 91 [+10] will be done.

CORE-OLE: A Study of Olezarsen (ISIS 678354) Administered Subcutaneously to Participants With Severe Hypertriglyceridemia (SHTG)

This is a multi-center, open-label extension (OLE) study of approximately 800 participants with SHTG who would be rolled over from studies ISIS 678354-CS5 (NCT05079919) or ISIS 678354-CS6 (NCT05552326). Day 1 of this study may be same as the Week 53 visit of either ISIS 678354-CS5 or ISIS 678354-CS6, as applicable. Participants will receive olezarsen during the 157-week treatment period. The study will include a 31-day qualification Period, a 157-week treatment period, and a 13-week post-treatment period.

Merit WRAPSODY™ Endoprosthesis for Treatment of Stenosis or Occlusion (WRAP)

Prospective, multicenter, observational study to evaluate the Merit WRAPSODY™ Endoprosthesis for treatment of stenosis or occlusion within the dialysis outflow circuit of an arteriovenous (AV) fistula or AV graft (The WRAP Registry)