Adjunctive Pascolizumab in Rifampicin-Susceptible Pulmonary Tuberculosis: Proof-of-Concept, Partially-Randomized, Double-Blind, Placebo-Controlled, Dose-Escalation Trial.

Background: Interleukin 4 (IL-4), increased in tuberculosis infection, may impair bacterial killing. Blocking IL-4 confers benefit in animal models. We evaluated safety and efficacy of pascolizumab (humanized anti-IL-4 monoclonal antibody) as adjunctive tuberculosis treatment.

Rosuvastatin adjunctive therapy for rifampicin-susceptible pulmonary tuberculosis: a phase 2b, randomised, open-label, multicentre trial.

Background: Shorter treatments are needed for drug-susceptible tuberculosis. Adjunctive statins increase bactericidal activity in preclinical tuberculosis models. We investigated the safety and efficacy of adjunctive rosuvastatin in people with tuberculosis.

Treatment Strategy for Rifampin-Susceptible Tuberculosis.

Background: Tuberculosis is usually treated with a 6-month rifampin-based regimen. Whether a strategy involving shorter initial treatment may lead to similar outcomes is unclear.

Methods: In this adaptive, open-label, noninferiority trial, we randomly assigned participants with rifampin-susceptible pulmonary tuberculosis to undergo either standard treatment (rifampin and isoniazid for 24 weeks with pyrazinamide and ethambutol for the first 8 weeks) or a strategy involving initial treatment with an 8-week regimen, extended treatment for persistent clinical disease, monitoring after treatment, and retreatment for relapse.

Pre- and apnoeic high-flow oxygenation for rapid sequence intubation in the emergency department (the Pre-AeRATE trial): A multicentre randomised controlled trial.

Introduction: Evidence regarding the efficacy of high-flow nasal cannula (HFNC) oxygenation for preoxygenation and apnoeic oxygenation is conflicting. Our objective is to evaluate whether HFNC oxygenation for preoxygenation and apnoeic oxygenation maintains higher oxygen saturation (SpO) during rapid sequence intubation (RSI) in ED patients compared to usual care.

Methods: This was a multicentre, open-label, randomised controlled trial in adult ED patients requiring RSI.

Effects of Increasing Concentrations of Rifampicin on Different Mycobacterium tuberculosis Lineages in a Whole-Blood Bactericidal Activity Assay.

High-dose rifampicin improved bactericidal activity and culture conversion in early-phase tuberculosis (TB) trials, done mainly in Africa. We performed a whole-blood bactericidal activity (WBA) study to determine whether the effects of high-dose rifampicin differ across globally relevant TB strains and whether effects are similar in dormant bacilli that will be required for enhancing cure. Whole blood from healthy volunteers was spiked with rifampicin (range, 0.

Alzheimer's Disease THErapy With NEuroaid (ATHENE): A Randomized Double-Blind Delayed-Start Trial.

Objectives: Preclinical and clinical studies indicate a role for MLC901 (NeuroAiD II) in Alzheimer's disease (AD). The primary aim was to investigate its safety as add-on therapy to standard treatment and the secondary aims its effect on cognition and slowing disease progression.

Design: Randomized double-blind placebo-controlled delayed-start study.

The Singapore Asymptomatic Narrow Angles Laser Iridotomy Study: Five-Year Results of a Randomized Controlled Trial.

Purpose: To examine the efficacy of laser peripheral iridotomy (LPI) in patients who received a diagnosis of primary angle-closure suspect (PACS).

Design: Prospective, randomized controlled trial.

Participants: This multicenter, randomized controlled trial (ClinicalTrials.

NEURoaid II (MLC901) in cognitively Impaired not demenTEd patientS (NEURITES): A pilot double blind, placebo-controlled randomized trial.

Objective: To investigate the efficacy and safety of MLC901 in vascular cognitive impairment no dementia (VCIND) patients.

Design: This was a multi-center, double-blind, randomized, placebo-controlled pilot study.

Setting And Participant: VCIND patients from hospitals in Singapore (67), Vietnam (19), and the Philippines (17) were recruited and followed-up from March 2013 to April 2018.

Frequency and Clinical Impact of Serious Adverse Events on Post-Stroke Recovery with NeuroAiD (MLC601) versus Placebo: The CHInese Medicine Neuroaid Efficacy on Stroke Recovery Study.

Background: Most comparative clinical trials are designed to assess the treatment effect for efficacy endpoints, with less emphasis on the analysis of safety outcomes. However, an extensive analysis of safety data could demonstrate beneficial results in terms of effectiveness by reducing serious adverse events (SAEs), and their unfavourable clinical impact on the study population. We aimed to conduct an exploratory analysis of the CHInese Medicine Neuroaid Efficacy on Stroke recovery (CHIMES) study safety database comparing the frequency of SAEs and their clinical impacts among subjects having received MLC601 or placebo during the first 3 months post-stroke.

Impact of selective immune-cell depletion on growth of Mycobacterium tuberculosis (Mtb) in a whole-blood bactericidal activity (WBA) assay.

We investigated the contribution of host immune cells to bacterial killing in a whole-blood bactericidal activity (WBA) assay, an ex vivo model used to test efficacy of drugs against mycobacterium tuberculosis (Mtb). We performed WBA assays with immuno-magnetic depletion of specific cell types, in the presence or absence of rifampicin. Innate immune cells decreased Mtb growth in absence of drug, but appeared to diminish the cidal activity of rifampicin, possibly attributable to intracellular bacterial sequestration.

Pre- and Apnoeic high flow oxygenation for RApid sequence intubation in The Emergency department (Pre-AeRATE): study protocol for a multicentre, randomised controlled trial.

Background: Maintaining adequate oxygenation during rapid sequence intubation (RSI) is imperative to prevent peri-intubation adverse events that can lead to increased duration of hospital and intensive care unit stay, or a prolonged vegetative state requiring long-term institutionalisation. Despite employing current best practices during RSI, desaturation during intubation still occurs. High-flow nasal cannula (HFNC) oxygenation may potentially improve oxygenation during pre- and apnoeic oxygenation to allow a longer safe apnoeic time for RSI.

Adjunctive use of celecoxib with anti-tuberculosis drugs: evaluation in a whole-blood bactericidal activity model.

COX-2 inhibition may be of benefit in the treatment of tuberculosis (TB) through a number of pathways including efflux pump inhibition (increasing intracellular TB drug levels) and diverse effects on inflammation and the immune response. We investigated celecoxib (a COX-2 inhibitor) alone and with standard anti-tuberculosis drugs in the whole-blood bactericidal activity (WBA) model. Healthy volunteers took a single dose of celecoxib (400 mg), followed (after 1 week) by a single dose of either rifampicin (10 mg/kg) or pyrazinamide (25 mg/kg), followed (after 2 or 7 days respectively) by the same anti-tuberculosis drug with celecoxib.

Coadministration of Allopurinol To Increase Antimycobacterial Efficacy of Pyrazinamide as Evaluated in a Whole-Blood Bactericidal Activity Model.

Coadministering pyrazinamide (PZA) with the xanthine oxidase inhibitor allopurinol increases systemic levels of the active metabolite, pyrazinoic acid (POA), but the effects on bactericidal activity against tuberculosis are unknown. We randomized healthy volunteers to take a single dose of PZA (either 10 or 25 mg/kg of body weight) at the first visit and the same dose 7 days later, coadministered with allopurinol (100 mg daily; 2 days before to 1 day after the PZA dose). Blood was drawn at intervals until 48 h after each PZA dose, and drug levels were measured using liquid chromatography-tandem mass spectrometry.

Activity of faropenem with and without rifampicin against Mycobacterium tuberculosis: evaluation in a whole-blood bactericidal activity trial.

Background: Faropenem has in vitro activity against Mycobacterium tuberculosis (Mtb) and shows synergy with rifampicin. We tested this in a whole-blood bactericidal activity (WBA) trial.

Methods: We randomized healthy volunteers to receive a single oral dose of faropenem (600 mg) with amoxicillin/clavulanic acid (500/125 mg) ( n  =   8), rifampicin (10 mg/kg) ( n  =   14) or the combination rifampicin + faropenem + amoxicillin/clavulanic acid ( n  =   14).

Emergency Department Management of Sepsis Patients: A Randomized, Goal-Oriented, Noninvasive Sepsis Trial.

Study Objective: The noninvasive cardiac output monitor and passive leg-raising maneuver has been shown to be reasonably accurate in predicting fluid responsiveness in critically ill patients. We examine whether using a noninvasive protocol would result in more rapid lactate clearance after 3 hours in patients with severe sepsis and septic shock in the emergency department.

Methods: In this open-label randomized controlled trial, 122 adult patients with sepsis and serum lactate concentration of greater than or equal to 3.

Five-Year Clinical Trial on Atropine for the Treatment of Myopia 2: Myopia Control with Atropine 0.01% Eyedrops.

Purpose: To compare the safety and efficacy of different concentrations of atropine eyedrops in controlling myopia progression over 5 years.

Design: Randomized, double-masked clinical trial.

Participants: A total of 400 children originally randomized to receive atropine 0.

Risk factors for progressive myopia in the atropine therapy for myopia study.

Purpose: To investigate variables associated with myopic progression despite treatment in the Atropine in the Treatment of Myopia Study.

Design: Retrospective cohort study.

Methods: Two hundred of 400 children were randomized to receive atropine 1% in 1 eye only in this institutional study.

Safety and immunogenicity of a virus-like particle pandemic influenza A (H1N1) 2009 vaccine: results from a double-blinded, randomized Phase I clinical trial in healthy Asian volunteers.

Methods: A novel, fully bacterially produced recombinant virus-like particle (VLP) based influenza vaccine (gH1-Qbeta) against A/California/07/2009(H1N1) was tested in a double-blind, randomized phase I clinical trial at two clinical sites in Singapore. The trial evaluated the immunogenicity and safety of gH1-Qbeta in the presence or absence of alhydrogel adjuvant. Healthy adult volunteers with no or low pre-existing immunity against A/California/07/2009 (H1N1) were randomized to receive two intramuscular injections 21 days apart, with 100μg vaccine, containing 42μg hemagglutinin antigen.

Molecular analysis of infant fecal microbiota in an Asian at-risk cohort-correlates with infant and childhood eczema.

Background: Studies have suggested that selective microbial targets prevail in the fecal microbiota of infants with eczema. This study evaluated the composition of fecal microbiota of infants who developed eczema in the first 5 years of life and compared these with those of healthy controls.

Findings: Children who developed eczema in the first 2 years, those with eczema at 5 years of age and healthy controls were selected from the placebo arm of a birth cohort of at-risk infants participating in a randomized double-blind trial on the protective effects of supplemental probiotics in early life on allergic outcomes.

Supplementation with probiotics in the first 6 months of life did not protect against eczema and allergy in at-risk Asian infants: a 5-year follow-up.

Background: Healthy gut microflora is essential for oral tolerance and immunity. A promising approach to preventing allergic diseases in genetically at-risk infants is to introduce administration of probiotics early in life when their immune system is still relatively immature.

Objective: In this follow-up study, we aim to determine if early-life supplementation with strains of probiotics has any long-term effect on allergic outcomes.

Analysis of time-to-event data with nonuniform patient entry and loss to follow-up under a two-stage seamless adaptive design with weibull distribution.

In the pharmaceutical industry, a two-stage seamless adaptive design that combines two separate independent clinical trials into a single clinical study is commonly employed in clinical research and development. In practice, in the interest of shortening the development process, it is not uncommon to consider study endpoints with different treatment durations at different stages (Chow and Chang, 2006 ; Maca et al., 2006 ).