Pune Maharashtra, India

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.

Shortened Regimen for Drug-susceptible TB in Children

In previously untreated individuals with presumed drug-susceptible pulmonary and or peripheral lymph node TB treated with eight weeks of rifapentine, isoniazid, pyrazinamide and moxifloxacin (2HPZM), all given daily throughout, the proportion of participants who experience absence of cure (unsuccessful outcome) will not be inferior to that observed in participants who are treated with the standard regimen (eight weeks of rifampin, isoniazid, pyrazinamide, with or without ethambutol followed by 8 to 16 weeks of rifampin plus isoniazid depending on disease severity) all given daily throughout.

POEM-F for Achalasia International Study

Achalasia is the most common esophageal motility disorder worldwide, with an annual incidence of 1.6 per 100'000 individual and prevalence of 10 per 100'000 population. The incidence of achalasia has been dramatically rising over the past decade. A study conducted in Chicago suggested that over the 10 years from 2004 to 2014, the incidence and prevalence of achalasia were two- to threefold greater than estimates would have predicted. The likely explanation to the rise in incidence is an increased awareness of this condition and widespread availability of accurate diagnostic test with high resolution manometry. The cardinal features of achalasia include failed relaxation of lower esophageal sphincter and absent esophageal peristalsis. Owing to the benign nature of the disease, patients suffering from it would experience longstanding debilitating symptoms of dysphagia, chest pain, regurgitation, resulting in poor quality of life. In the past, laparoscopic Heller's cardiomyotomy with partial fundoplication and endoscopic pneumatic dilatation were considered as treatment options for achalasia. In the past 10 years, per-oral endoscopic myotomy (POEM) has emerged as the incisionless minimally invasive endoscopic treatment of choice for achalasia. This Natural Orifice Transluminal Endoscopic Surgical (NOTES) technique involves mucosal incision and creation of a submucosal tunnel in the distal esophagus down to gastric cardia, followed by esophageal and gastric myotomy. Since the procedure was first reported by Inoue H, et al in 2010, it has seen worldwide acceptance as first-line therapy. POEM has been associated with excellent relief of dysphagia and achalasia-related symptoms with a low and acceptable adverse event rate of 0.5%. In a previous randomised controlled trial, POEM had a higher treatment success rate than pneumatic dilatation. When compared with laparoscopic Heller's cardiomyotomy, POEM was associated with at least similar treatment efficacy and a trend towards reduced short term adverse event. POEM could perform even better than surgical myotomy in patients with type III achalasia. The main limitation of POEM is the incidence of gastroesophageal reflux disease (GERD) post-POEM. Kumbhari et al. looked at rates of GERD after POEM on patients who underwent subsequent objective pH testing. A total of 282 patients were included in this analysis from multiple centers in America, Asia, and Europe. About 58% of patients had objective evidence of abnormal acid exposure, with 23% showing evidence of esophagitis. More concerning, however, was that 60% of the patients with GERD were completely asymptomatic. This highlights an important issue at hand that many patients, either related to the propensity of GERD to be silent or the nature of achalasia to develop and insensate esophagus, do not report symptoms while showing high rates of GERD. POEM has been found to be consistently associated with higher rate of GERD than conventional Heller's cardiomyotomy or pneumatic dilatation across multiple studies. Supported by evidence demonstrating the efficacy of partial fundoplication during Heller's operation, there has been a significant interest in performing fundoplication after POEM during the same session to prevent the development of post-POEM GERD. Inoue et al. pioneered the technique of POEM-F that mimics the surgical Dor (anterior partial fundoplication) procedure. In the pilot study, technical success was achieved in all 21 patients, and all but one had an intact fundoplication wrap on upper endoscopy at a 1-month follow-up. Four more studies conducted in Japan and India have reported good early outcomes with POEM-F (Technical success of 85-100%) for achalasia. No severe adverse event has been reported in these studies which reiterates the safety of this procedure. In the longest follow-up study on POEM-F, GERD diagnosed by an abnormal esophageal acid exposure was seen in 11.1% of the 21 cases at one-year follow-up: comparable (8.8%) to a large meta-analysis of 4871 Heller's cardiomyotomy with fundoplication procedures. To date, no prospective multicenter randomised study has been conducted to compare the efficacy of POEM-F with conventional POEM in reducing post-procedure GERD. Therefore, in this study, the investigators aim to evaluate the of POEM-F in patients with achalasia through an international multicenter randomized controlled trial.

Study of a Single Dose of Pretomanid Added to an Optimized Background Regimen in Children With Rifampicin-Resistant Tuberculosis

This is a Phase I, multi-site, open-label, non-comparative study of the PK, safety, tolerability, and acceptability of a single-dose of pretomanid added to an OBR in infants, children, and adolescents with RR-TB. The term children is used within the protocol to indicate the total age range from infants through adolescents; enrollment will be limited to children assigned female sex at birth and enrollment of neonates will be deferred until safety and pharmacokinetic data are available in older groups, pending review by the CMC and SMC during the interim analysis. Refer to the study design and the study eligibility criteria and a description of the study recruitment, screening, and enrollment process. Participants are expected to be enrolled at study sites in Brazil, India, South Africa and Thailand. Up to 72 participants will be enrolled to achieve at least nine evaluable participants in each of four weight groups, for a total of at least 36 enrolled participants. Participants will receive a single dose of pretomanid on the day of study entry. No additional doses of pretomanid will be administered; participants will continue their OBR. Intensive PK sampling and safety monitoring will be performed on the day of study entry and over the course of the next 48 hours. Participants will then complete a final study visit approximately two weeks after study entry.

Impact of Treatment With ALVEOGYL in Patients With Post-extraction Dry Socket

A Study to Determine the Validity and Sensitivity of 'Questionnaire to Screen for HYpothyroidism' (Q'SHY)

Objectives The objectives of the study are as described in the below points. 1. To develop a questionnaire (Q'SHY) for the identification and screening of subjects with suspected hypothyroidism. 2. To assess the validity of the designed questionnaire by comparing the outcomes of the responses between General population subjects and treatment naïve subjects group with hypothyroidism. 3. The study aims to establish a valid questionnaire with a robust sensitivity and specificity to detect signs and symptoms of hypothyroidism. Inclusion criteria for Subjects The criteria based on which, subjects in each Arm will be chosen to take part in the survey. Arm1: Subjects from the general population who are naïve to their hypothyroid status. - Male and female subjects between the age of 18 years and 65 years - Willing to sign the Subject Authorization Form (SAF) Arm 2: Subjects who are newly diagnosed patients of Hypothyroidism and are treatment naïve*. - Male and female subjects between the ages 18 years and 65 years. - Subjects who had symptoms of hypothyroidism were seen by a physician and diagnosed with hypothyroidism after laboratory testing of Thyroid Stimulating Hormone > 4.5 Milli international units per litre(mIU/L) within 2 weeks from the date of the survey - Willing to sign the SAF - Willing to provide their Thyroid Function Test report that was used to diagnose Hypothyroidism. * Treatment naive diagnosed on basis lab and clinical diagnosis within last 2 weeks Exclusion criteria for subjects Arm 1: Subjects from the general population who are naïve to their hypothyroid status - Individuals less than 18 years of age and more than 65 years of age. - Pregnant or lactating females Subjects previously diagnosed with and received treatment for thyroid diseases. - Subjects not willing to sign the SAF. Arm 2: Subjects who are newly diagnosed patients of Hypothyroidism and are treatment naïve - Individuals less than 18 years of age and more than 65 years of age. - Pregnant or lactating females - Subjects previously diagnosed with and received treatment for thyroid diseases. - Patients on treatment for Thyroid diseases Subjects not willing to sign the SAF. The above-mentioned criteria will be applicable to both Face validation and Pilot survey. 1. Subjects are divided into 2 arms, with 100 subjects in each arm. 2. Phase -1 - Arm 1: Sixteen subjects from the general population who are naïve to their hypothyroid status with equal distribution of males and females. - Arm 2: Sixteen subjects who are newly diagnosed patients of Hypothyroidism are treatment naïve with equal distribution of males and females 3. Phase -2 - Arm 1: One hundred subjects from the general population who are naïve to their hypothyroid status with equal distribution of males and females - Arm 2: One hundred subjects who are newly diagnosed patients of Hypothyroidism are treatment naïve with equal distribution of males and females

Anticoagulation for Stroke Prevention In Patients With Recent Episodes of Perioperative AF After Noncardiac Surgery

ASPIRE-AF is a prospective, randomized, open-label trial of non-vitamin K oral anticoagulants (NOACs) versus no oral anticoagulation in patients with transient perioperative atrial fibrillation and additional stroke factors after noncardiac surgery. The primary objective is to assess the effects of NOACs versus no anticoagulation on the co-primary composite outcomes of 1. non-hemorrhagic stroke and systemic embolism, and 2. vascular mortality, and non-fatal non-hemorrhagic stroke, myocardial infarction, peripheral arterial thrombosis, amputation, and symptomatic venous thromboembolism over the duration of follow-up.

A Study of Tildrakizumab in Pediatric Subjects With Chronic Plaque Psoriasis

Study to Evaluate the Efficacy, Safety, and Tolerability of IMU-838 in Patients With Relapsing Multiple Sclerosis

This study will be a multicenter, randomized, double-blind, placebo-controlled study with a blinded Main Treatment Period (MT) and an Open Label Period (OLE) to evaluate the efficacy, safety, and tolerability of IMU-838 in adult patients with RMS. The study will consist of the following periods: Screening Period: Approximately 28 days Main Treatment Period: Up to 72 weeks (approximately 15 months) Open Label Extension Period: Up to approximately 8 years

Timing of Necrosectomy After Endoscopic Drainage of Walled-off Pancreatic Necrosis (WON)

INTRODUCTION Acute pancreatitis is one of the most common gastrointestinal diseases requiring emergency admissions to the hospital. 10-20% of these patients develop pancreatic necrosis and subsequent walled-off pancreatic necrosis (WON) and is associated with a mortality of 20-30%. Grade 1A evidence exists to support an initial minimally invasive drainage approach to infected WON. However, the optimal approach and timing of necrosectomy remains unaddressed. The current suggested approach in international guidelines is the endoscopic step-up approach. However, recent evidence from large national cohorts support the use of direct endoscopic necrosectomy (DEN) at the time of stent placement, resulting in earlier resolution of WON and less number of necrosectomies. OBJECTIVE This study aims to investigate the clinical outcomes of the DEN versus the step-up approach for necrosectomy after endoscopic drainage of WON. HYPOTHESIS The hypothesis is that DEN at the time of LAMS placement improves clinical outcomes after endoscopic drainage of WON as compared to the endoscopic step-up approach. DESIGN AND SUBJECTS This is a multicentre international randomized controlled trial. Patients with suspected or confirmed infected or symptomatic WON on computed tomography (CT) and who are deemed feasible for endoscopic drainage will be included in the study. Endoscopic drainage with lumen-apposing metal stents (LAMS) will be performed. Patients will be randomised to either the endoscopic step-up approach or direct endoscopic necrosectomy (DEN) approach. The primary endpoint is a composite of major complications or death within 6 months after randomisation. Secondary endpoints include time to resolution of WON, pancreatic functions, biliary strictures, need for necrosectomy, total number of interventions, length of hospital and ICU stay, recurrence of WON and unplanned readmissions related to WON. A reduction in cumulative primary endpoint with the DEN approach by 22.4% (32.2% to 9.8%) in comparison to endoscopic step-up approach was assumed. With a 2-sided significance level of 5% and power of 80%, taking into account a 5% drop-out rate, a total of 108 patients was required to demonstrate this effect. Study collaboration has been established with four other international centres. A estimation of 3 years is required to complete study recruitment.