Clinical trials

The present longitudinal, randomized, and blinded clinical trial aims to: * Evaluate the effects of resistance training on the functional capacity, quality of life, and cardiac biomarkers of hospitalized patients with heart failure (HF) on the waiting list for heart transplantation (HTx). * Evaluate the associations between Fried's frailty classification and functional capacity responses to resistance training. The protocol will have a total duration of 12 weeks.

The goal of this observational and prospective study is to investigate changes in physical performance, lung function, respiratory and peripheral muscle strength in patients during the postoperative period following pulmonary endarterectomy (PET).

The objective of this randomized clinical trial is to compare the effects of a standardized exercise program alone versus the same program combined with neuromuscular electrical stimulation in patients undergoing heart failure . The main questions it aims to answer are: * Assessing the ultrasonographic parameters: echo intensity (echogenicity), cross-sectional area, thickness, and pennation angle of the rectus femoris muscle in both lower limbs. * Evaluating the strength of the femoral quadriceps muscle * Evaluating the changes in the chronaxie of the rectus femoris muscle in both lower limbs. The protocol will have a total duration of 32 days, with an initial intervention period of 18 days, followed by a 14-day follow-up period.

To assess the importance of using SBRT-LATTICE-PATHY for the radiotherapy treatment of large tumors that would be considered intractable by currently used standard techniques. In this present study, the investigators will have the possibility of combining SBRT and LATTICE techniques, incorporating the concept of hypoxic tissue irradiation, which are potential modulators of abscopal and bystander effects, performing partial punctual treatment in the vertex region, without the need for irradiation of the entire tissue volume, further improving safety in relation to possible toxicities.

Hepatic reperfusion during liver transplantation remains a critical phase associated with significant hemodynamic and systemic disturbances, despite advances in surgical and anesthetic management. This phase is characterized by the release of acidotic, hypothermic, and hyperkalemic blood containing metabolic byproducts and inflammatory mediators resulting from ischemia-reperfusion injury. Clinically, reperfusion is associated with hemodynamic instability, including reductions in cardiac output and arterial pressure, as well as cardiac dysfunction and arrhythmias, often requiring pharmacologic support. These alterations may affect not only immediate intraoperative stability but also short- and long-term outcomes for both the patient and the graft. The abrupt restoration of blood flow to the transplanted liver leads to the systemic release of accumulated metabolites, reactive oxygen species, and inflammatory mediators, contributing to a systemic inflammatory response that may impact distant organs, including the kidneys and heart. Several revascularization strategies have been investigated to mitigate reperfusion-related injury: initial reperfusion via the portal vein, initial reperfusion through the hepatic artery, and simultaneous reperfusion through the portal vein and hepatic artery. A less frequently used and insufficiently studied strategy, not routinely or systematically implemented, involves diverting the initial reperfusion blood from the graft to the surgical field, followed by the restoration of hepatic blood outflow to the systemic circulation. This study hypothesizes that discarding the initial reperfusion blood via the infrahepatic vena cava will attenuate early hemodynamic, metabolic, and inflammatory changes and reduce postoperative complications compared to conventional reperfusion techniques.

The goal of this clinical trial is to evaluate whether hypothermic machine perfusion improves liver graft preservation and post-transplant outcomes compared to conventional static cold storage in adult patients undergoing liver transplantation. This study focuses on liver grafts from deceased donors, including those with extended criteria, which are more susceptible to ischemia-reperfusion injury and early graft dysfunction. The main questions it aims to answer are: Does hypothermic machine perfusion reduce ischemia-reperfusion injury and improve early graft function after liver transplantation? Does this preservation strategy improve clinical outcomes, including graft survival, complication rates, and post-transplant recovery, compared to static cold storage? Researchers will compare hypothermic machine perfusion (ex situ, oxygenated perfusion at low temperature) to standard static cold storage to assess differences in graft preservation quality and post-transplant outcomes. Participants will: Receive a liver graft preserved either by hypothermic machine perfusion or static cold storage, according to a 1:1 randomization protocol Undergo standard liver transplantation procedures Be followed after transplantation with clinical, laboratory, imaging, and biomarker assessments at predefined time points (7 days, 30 days, 6 months, and 1 year) Additional evaluations will include biochemical markers of liver function, inflammatory and immunological mediators, mitochondrial function assessment, and histological analysis to better characterize graft injury and recovery.

Chronic thromboembolic pulmonary hypertension (CTEPH) is a condition in which old blood clots block the blood vessels in the lungs, making it harder for the heart to pump blood through the lungs. Surgery called pulmonary thromboendarterectomy can remove these clots and improve blood flow, but doctors need reliable ways to evaluate lung blood flow before and after surgery. This study will evaluate a bedside imaging method called electrical impedance tomography (EIT), which can measure how blood flows through different regions of the lungs without radiation or invasive procedures. Patients undergoing surgery for CTEPH will be monitored with EIT before and after surgery, and the results will be compared with standard lung perfusion imaging. The goal of this study is to determine whether EIT can provide useful information about lung blood flow and changes after surgery, and whether it could serve as a complementary bedside tool to help monitor patients with CTEPH.

Gestational diabetes mellitus (GDM) is one of the most common clinical conditions in pregnancy, with an increasing incidence due to the rise in overweight women and the postponement of motherhood. It is associated with perinatal complications and an increased risk of developing prediabetes and type 2 diabetes after delivery. Therefore, it is recommended that a 75g oral glucose tolerance test (OGTT-75g) be performed between 6 and 12 weeks postpartum. Despite its relevance, the rate of adherence to the test is low. Recent studies also indicate that measuring blood glucose one hour after the overload may be more sensitive than the traditional two-hour measurement in the early detection of dysglycemia. This study aims to evaluate strategies for qualifying the screening of metabolic changes in the postpartum period among women with GDM. The objectives are: (1) to analyze the impact of sending reminders via WhatsApp on the attendance rate for the 75g OGTT; and (2) to compare the frequency of prediabetes and diabetes diagnoses using two different diagnostic strategies applied to the same test-the traditional (fasting and 2-hour blood glucose) and the alternative (fasting and 1-hour blood glucose).

This randomized, double-blind, placebo-controlled clinical trial aims to evaluate whether single-dose amoxicillin prophylaxis administered prior to simple tooth extraction reduces postoperative infection rates in immunosuppressed patients with autoimmune rheumatic diseases (ARDs). Although antibiotic prophylaxis is not recommended for healthy individuals undergoing simple extractions, immunosuppressed ARD patients frequently receive antibiotics despite limited evidence supporting this practice. Secondary objectives include assessing infection severity, postoperative complications, and the impact of ARD diagnosis and immunosuppressive treatment on infection risk.

The goal of this clinical trial is to evaluate the humoral immunogenicity of the meningococcal B vaccine (MenB-4C) in pediatric patients with autoimmune rheumatic diseases (ARDs), compared to age- and sex-matched non-immunosuppressed controls. The main questions it aims to answer are: * To assess the influence of treatment on the response to the MenB-4C vaccine in patients with ARDs; * To evaluate the impact of the MenB-4C vaccine on disease activity in patients with ARDs; * To evaluate the safety of the MenB-4C vaccine in pediatric patients with ARDs and controls. * To evaluate the association between physical activity levels and immunogenicity after vaccination. Participants will: Receive the MenB-4C vaccine (Bexsero©), administered intramuscularly in the deltoid muscle, in a 2-dose schedule (0.5 mL each), 1 month apart. All participants will have blood samples collected immediately before vaccination at the baseline visit (D0), then receive the first vaccine dose on the same day (D0). The second dose will be administered 4 weeks after the first dose (D28). Blood samples will be collected on D0, D28, and D56. A final sample will be collected one year after the last dose (D208) to evaluate the persistence of immune response. At study entry and one month after each dose, patients will also be assessed for clinical and laboratory disease activity using disease-specific indices and scores. * Juvenile Systemic lupus erythematosus (JSLE): Systemic lupus erythematosus disease activity index 2000 (SLEDAI-2K) (CBC, anti-dsDNA, complement, urinalysis, protein/creatinine ratio) * Juvenile Idiopatic Arthritis (JIA): Juvenile Arthritis Disease Activity Score (JADAS) (ESR, CRP) * Juvenile dermatomyositis (JDM): Manual Muscle Testing (MMT) e Childhood Myositis Assessment Scale (CMAS): (CPK, transaminases, LDH) Researcher will also perform analysis in: Humoral immunogenicity will be assessed using serum bactericidal activity (SBA) assay with exogenous complement (baby rabbit, Pel Freez) against four test strains: H44/76 (fHBP), 5/99 (NadA), NZ98/254 (PorA), and M10713 (NHBA), from blood samples collected at D0, D28, D56, and D208. SBA assays will be conducted at the Immunology Center of the Adolfo Lutz Institute, São Paulo. Exogenous complement will be added to serially diluted serum samples, followed by the addition of a bacterial suspension. The humoral response rate induced by the vaccine, or seroconversion, will be defined by the bactericidal titer (the dilution that results in 50% bacterial killing within 60 minutes compared to the control), with titers ≥ 1:4 considered bactericidal. The geometric mean titers will be calculated using the exponential of the mean of the log-transformed concentrations. Immunosuppressive treatments (NSAIDs, prednisone/prednisolone, intra-articular steroids, hydroxychloroquine, methotrexate, azathioprine, leflunomide, cyclosporine, tacrolimus, mycophenolate mofetil, and biologics \[anti-TNF, tocilizumab, abatacept, belimumab, rituximab\]) will be recorded sistematicaly. Physical activity levels will be assessed using validated, age-appropriate methods.

The goal of this clinical trial is to evaluate whether the live attenuated tetravalent Butantan-Dengue vaccine (Butantan-DV) is safe and capable of inducing an immune response in patients aged 12 to 59 years with autoimmune rheumatic diseases (ARDs) who are clinically stable and under low-grade or no immunosuppression, as well as in healthy volunteers matched by sex and age. The main questions it aims to answer are: Does the vaccine induce adequate seroconversion in patients with ARDs compared to healthy controls? What is the frequency and intensity of common adverse events after vaccination in ARDs patients? Does physical activity levels and nutritional status influence vaccine-induced immune response in patients with ARDs? Researchers will compare patients with ARDs to healthy controls to evaluate if the vaccine elicits similar immune responses and safety profiles. All participants will: * receive a single 0.5 mL dose of the Butantan-DV vaccine via subcutaneous injection; * undergo blood sample collection before and after vaccination (baseline, Day 42, and Day 400) to assess antibody and cellular responses; * attend follow-up visits on Days 7, 14, and 42 for safety monitoring and laboratory tests; * report any symptoms or adverse events using a standardized diary for 42 days; * be followed for up to one year for long-term safety and immunogenicity assessments. * wear a device for 14 consecutive days to assess current and habitual physical activity levels. * answer three non-consecutive 24-hour dietary recalls, including at least one weekend day to assess nutritional status. * collect blood samples one-year after vaccination to access immunogenicity and cellular response. Researcher will also perform subgroups analysis in: A viremia subgroup (50 patients and 50 healthy controls) will provide additional samples on Days 1, 7, 14, 28, 42, and-if viremia is detected-Day 68, to evaluate post-vaccination viremia and its duration. An immunogenicity subgroup (\~20% of participants, n=96) will undergo cellular immune response testing via flow cytometry to evaluate T-cell responses.

The objective of the study is to evaluate the effectiveness of extracorporeal shock wave therapy (ESWT) in improving pain in patients with TMD pain after 5 weeks of treatment, 1 month and 3 months after the end of treatment. As secondary objectives, we plan to evaluate the effectiveness of focal shockwave therapy in relation to: 1. Range of motion (ROM) of the temporomandibular joint using goniometry after 5 weeks of treatment; 2. Degree of inflammation, using ultrasound evaluation in the temporomandibular joint relating to the degree of pain after focal shockwave therapy for 5 weeks; 3. Jaw movement (MM), joint noise (RA), joint pressure (PA) and disability index (DI) will be measured at each treatment session and after 5 weeks of treatment, 1 month and 3 months after the end of treatment in the affected joints; 4. Quality of life will be assessed using the "Short Form Health 36" questionnaire (SF-36) during the 5 weeks of treatment, 1 month and 3 months after the end of treatment; 5. Pain control medication will also be considered and compared before and after the proposed treatment for 5 weeks. Safety will be assessed throughout the study by monitoring the incidence of study-related adverse events. All patients will be contacted periodically and encouraged to report any side effects.

This clinical trial aims to evaluate the effect of temporary methotrexate (MTX) discontinuation on the humoral immunogenicity of the 20-valent pneumococcal conjugate vaccine (PCV20) in adult patients with autoimmune rheumatic diseases (ARDs). Key questions: * Does suspending MTX for 2 weeks after PCV20 enhance humoral immunogenicity? * What is the impact of MTX discontinuation on functional opsonophagocytic activity (OPA) and cellular immunity? * What is the risk of disease flaring with MTX withdrawal?

The goal of this clinical trial is to find out whether the BESDATA BD-DF videolaryngoscope works as well as the McGRATH™ MAC videolaryngoscope for placing a breathing tube in infants during surgery. The study will also compare the costs associated with using each device. The main questions this study aims to answer are: Is the BESDATA BD-DF videolaryngoscope as effective as the McGRATH™ MAC videolaryngoscope for successful placement of a breathing tube on the first attempt in infants? Are there differences between the two devices in terms of procedure time, number of attempts, airway-related complications, and overall costs? Researchers will compare infants who are intubated using the BESDATA BD-DF videolaryngoscope with infants who are intubated using the McGRATH™ MAC videolaryngoscope to see whether the two devices perform similarly and whether one is more cost-effective than the other. Participants will: Be randomly assigned to have a breathing tube placed using one of the two videolaryngoscopes; Receive standard general anesthesia for an elective surgical procedure; Have information collected during and after the procedure to assess safety, effectiveness, and costs.

This study investigates the motor and non-motor effects of Low-Intensity Focused Ultrasound (LIFU) as a non-invasive neuromodulation technique in patients with essential tremor (ET) and refractory tremor. LIFU is a non-thermal, non-ablative form of transcranial focused ultrasound that modulates neural activity through mechanical mechanisms, including direct effects on neuronal membranes, alterations in membrane excitability, and modulation of synaptic transmission. Unlike high-intensity focused ultrasound (HIFU), which produces tissue ablation, LIFU induces reversible effects with a favorable safety profile, making it a promising candidate for non-invasive neuromodulation in movement disorders. In this randomized, double-blind, sham-controlled, crossover trial, 20 patients with ET and refractory tremor will receive active LIFU targeting the ventral intermediate nucleus (VIM) of the thalamus and sham stimulation in separate sessions, separated by a washout period of at least 12 weeks. Clinical assessments using standardized and validated neurological scales will be performed before and after each session to evaluate changes in motor symptoms, tremor severity, quality of life, and non-motor features. The primary outcome is the change in the Fahn-Tolosa-Marín Tremor Rating Scale (FTMTRS) and the Essential Tremor Rating Assessment Scale (TETRAS©). Secondary outcomes include the Patient Global Impression of Change (PGIC) and monitoring of adverse events. This study is being conducted at the Movement Disorders Center of Hospital das Clínicas, University of São Paulo (HC-FMUSP), São Paulo, Brazil, and has been approved by the institutional ethics committee (CAPPesq; approval number 7.406.027).

This will be a multicenter, prospective, randomized, open-label trial with women harboring microprolactinomas and treatment naïve. The sample will be added consecutively and randomized into 2 unblinded groups: the high dosage group will receive a high cabergoline (CAB) dose for a period of \~6 months vs the standard dosage group, which will use the lowest needed dose of CAB to achieve normoprolactinemia for 2 years. The primary outcome will be remission rate.

This methodological study aims to develop and validate a questionnaire named for the Assessment of Patient Knowledge in Pulmonary Arterial Hypertension. The study will be conducted in four phases: (1) questionnaire development based on guidelines and literature; (2) content validation by expert judges; (3) semantic validation with patients; and (4) psychometric testing in a sample of up to 200 patients with confirmed pulmonary arterial hypertension (PAH). In addition to validation, the study will collect clinical and functional data from medical records, including risk stratification using the COMPERA 2.0 method The final instrument is expected to support patient education strategies and contribute to improved clinical management of PAH.

This interventional phase IV clinical trial will evaluate the efficacy, immunogenicity and safety of the adjuvanted recombinant herpes zoster vaccine (RZV) in adults with autoimmune rheumatic diseases (ARDs) receiving immunomodulatory monotherapy. Humoral immune response will be quantified by anti-glycoprotein E (anti-gE) antibody titers. Patients will receive two doses of RZV. Outcomes include seroconversion and geometric mean titers six weeks after completion of the vaccination schedule, persistence of antibody titers at one year, and incidence of confirmed herpes zoster during follow-up.

Pulmonary Arterial Hypertension is a rare and progressive condition that compromises pulmonary circulation and can lead to right ventricular failure. Despite recent advances in diagnosis and treatment, the median survival of patients is only 2.8 years. The treatment for this disease is based on drugs that act on three main pathways: prostacyclin, endothelin, and nitric oxide. Iloprost, a prostacyclin analogue available in an inhaled form, is an important and well-established treatment. However, its mandatory frequent administration, the need for a specific inhalation technique, and its adverse event profile make its use complex. Although pharmacotherapeutic and inhalation technique follow-up by a qualified professional is widely studied in diseases like asthma and COPD, its application in Pulmonary Arterial Hypertension still lacks evidence. Thus, this study aims to evaluate how a pharmacist's intervention can improve treatment adherence, mitigate side effects and difficulties associated with inhalation, in addition to optimizing clinical and hemodynamic outcomes in patients with Pulmonary Arterial Hypertension using iloprost.

The goal of this randomized, double-blind, placebo-controlled clinical trial is to evaluate the effectiveness and safety of oral suppressive therapy with acyclovir in preventing herpes simplex virus (HSV) reactivation in patients with autoimmune rheumatic diseases (ARDs) who have a history of recurrent HS episodes. The main questions this study aims to answer are: Does continuous oral acyclovir reduce the frequency of HSV reactivation in ARD patients compared to placebo? What is the safety profile of prolonged acyclovir use in this population? What are the main risk factors (clinical and treatment-related) associated with HSV reactivation in immunosuppressed patients. Participants will: Be randomly assigned (1:1) to receive oral acyclovir (400 mg BID) or placebo for 12 months; Be followed for a total of 24 months, with regular clinical evaluations (every 3 months) and laboratory monitoring (every 3 months); Be assessed for HSV recurrence based on clinical symptoms, detection of HSV DNA by polymerase chain reaction (PCR) in mucocutaneous swabs in doubtful cases, and standardized reporting forms; Undergo disease activity assessments and adverse event monitoring at regular intervals. The study includes adult and pediatric patients with confirmed diagnoses of one of the following ARDs: systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), juvenile idiopathic arthritis (JIA), ankylosing spondylitis (AS), psoriatic arthritis (PsA), dermatomyositis/polymyositis (DM/PM), systemic sclerosis (SSc), systemic vasculitis, primary Sjögren's syndrome, Mixed connective tissue disease (MCTD), Chronic recurrent multifocal osteomyelitis (CRMO), Sarcoidosis and Behçet's Syndrome. All participants must have a documented history of recurrent HSV (oral and/or genital) before inclusion.

This clinical trial evaluates the immunogenicity (humoral and cellular) and safety of the 20-valent pneumococcal conjugate vaccine (PCV20) in children, adolescents, and young adults aged 2-25 years with autoimmune rheumatic diseases (ARDs). All participants will receive PCV20 according to prior vaccine history. Antibody titers, opsonophagocytic activity, cellular immune responses, and adverse events will be measured up to 6 months post-vaccination. Effects of immunosuppressive therapy and physical activity levels related vaccine response will also be assessed.

Sjögren's disease (SjD) is a chronic, immune-mediated, systemic inflammatory disease characterized mainly by involvement of the salivary and lacrimal glands, causing symptoms of sicca syndrome. The disease predominantly affects women (9:1 to 20:1), with a peak incidence between 40 and 60 years of age. Symptoms of dryness include those resulting from vaginitis sicca, such as vulvovaginal irritation, dryness, pruritus, dyspareunia, polyuria, nocturia, dysuria, and urinary urgency/incontinence, which may begin before and worsen after menopause. These symptoms impact the sexual life and health-related quality of life of SjD patients. However, there are no specific recommendations for the management of vaginal dryness in this disease. Urogenital syndrome (UGS), a condition that affects women from the general population in the menopausal phase, is characterized by similar symptoms and can be treated with systemic or local hormone therapy (e.g., topical promestriene). Current data also demonstrate the efficacy and safety of vaginal fractional CO2 laser treatment for UGS. However, there are no studies on the efficacy of vaginal fractional CO2 laser and topical promestriene in the treatment of vaginal dryness in SjD.

Pulmonary hypertension is a serious and progressive disease that is difficult to treat and diagnose, mainly because its symptoms are nonspecific and often delay recognition. Early diagnosis is a major challenge. Although several tests may suggest the disease, the definitive diagnosis still requires right heart catheterization, an invasive procedure that directly measures pulmonary hemodynamics such as pulmonary artery pressure, cardiac output, and vascular resistance. Electrical impedance tomography (EIT) is a non-invasive, radiation-free bedside monitoring method that can evaluate ventilation and pulmonary perfusion. The number of studies investigating perfusion with EIT has been increasing, since the possibility of having a safe, radiation-free, and repeatable method available at the bedside is of great clinical interest in different fields of medicine. Our hypothesis is that EIT provides information that correlates with the findings of right heart catheterization in patients with suspected pulmonary arterial hypertension (PAH). EIT may serve as a useful screening tool prior to catheterization and may also help in risk stratification of patients with pulmonary hypertension

Vertigo and dizziness are common neurological complaints in the emergency department and may represent a wide spectrum of etiologies, including vertebrobasilar transient neurological attacks (VB-TNAs). Distinguishing VB-TNAs, particularly vertebrobasilar transient ischemic attacks (VB-TIAs), from migraine-like and other non-vascular conditions is often challenging at first presentation due to the absence of specific biomarkers and overlapping clinical features. The UTRAVERA study is a multicenter, prospective, observational investigation designed to characterize the clinical features of patients presenting with acute transient vertigo or dizziness suspected to be VB-TNAs. The study will also evaluate diagnostic evolution over time, treatment responses, and prognostic factors associated with clinical outcomes.

This is a single-center, randomized intervention study in a volunteer population of patients with cocaine/crack use disorder to evaluate the pharmacological treatment of cocaine/crack craving, comparing the drug clonidine with the active placebo clonazepam.