Targeted oxygenation in the respiratory care of premature infants at delivery-effects on outcome: a randomised controlled trial (Torpido 3060) study protocol.

Introduction: The safest oxygen levels needed for preterm infant respiratory support at birth are uncertain. We aimed to compare the outcomes of infants up to 28 weeks gestation who had respiratory care initiated at birth with fractional inspired oxygen (FiO) 0.3 or 0.

INTEGRATE II: randomised phase III controlled trials of regorafenib containing regimens versus standard of care in refractory Advanced Gastro-Oesophageal Cancer (AGOC): a study by the Australasian Gastro-Intestinal Trials Group (AGITG).

Background: Advanced gastro-oesophageal cancer (AGOC) carries a poor prognosis. No standard of care treatment options are available after first and second-line therapies. Regorafenib is an oral multi-targeted tyrosine kinase inhibitor targeting angiogenic, stromal, and oncogenic receptor tyrosine kinases.

Value of central review of RECIST v1.1 outcomes in the AGITG INTEGRATE randomised phase 2 international trial for advanced oesophago-gastric cancer.

Purpose: Activity estimates should be accurately evaluated in phase 2 clinical trials to ensure appropriate decisions about proceeding to phase 3 trials. RECIST v1.1.

Patient-Reported Bowel, Urinary, and Sexual Outcomes After Laparoscopic-Assisted Resection or Open Resection for Rectal Cancer: The Australasian Laparoscopic Cancer of the Rectum Randomized Clinical Trial (ALaCart).

Objective: The aim of this study was to compare patient-reported urinary, bowel, and sexual functioning of ALaCaRT Trial participants randomized to open or laparoscopic surgery for rectal cancer.

Summary Background Data: The primary endpoint, noninferiority of laparoscopic surgical resection adequacy, was not established.

Methods: Participants completed QLQ-CR29 at baseline, 3, and 12 months post-surgery.

Health-Related Quality of Life in Metastatic, Hormone-Sensitive Prostate Cancer: ENZAMET (ANZUP 1304), an International, Randomized Phase III Trial Led by ANZUP.

Purpose: We previously reported that enzalutamide improved overall survival when added to standard of care in metastatic, hormone-sensitive prostate cancer. Here, we report its effects on aspects of health-related quality of life (HRQL).

Methods: HRQL was assessed with the European Organisation for Research and Treatment of Cancer core quality-of-life questionnaire and QLM-PR25 at weeks 0, 4, 12, and then every 12 weeks until progression.

Effects of delayed versus immediate umbilical cord clamping in reducing death or major disability at 2 years corrected age among very preterm infants (APTS): a multicentre, randomised clinical trial.

Background: Very preterm infants are at increased risk of adverse outcomes in early childhood. We assessed whether delayed clamping of the umbilical cord reduces mortality or major disability at 2 years in the APTS Childhood Follow Up Study.

Methods: In this long-term follow-up analysis of the multicentre, randomised APTS trial in 25 centres in seven countries, infants (<30 weeks gestation) were randomly assigned before birth (1:1) to have clinicians aim to delay clamping for 60 s or more or clamp within 10 s of birth, both without cord milking.

Healthcare Costs of Laparoscopic versus Open Surgery for Rectal Cancer Patients in the First 12 Months: A Secondary Endpoint Analysis of the Australasian Laparoscopic Cancer of the Rectum Trial (ALaCaRT).

Background: Laparoscopic-assisted surgery for rectal cancer is widely used, however the healthcare costs are thought to be higher than for open resection. This secondary endpoint analysis of a randomized controlled trial aimed to evaluate total healthcare costs of laparoscopic-assisted surgery compared with open resection for rectal cancer over a 12-month period.

Methods: Patients in the Australasian Laparoscopic Cancer of the Rectum Trial (ALaCaRT) were included in a prospective costing analysis.

Overall Survival of Men with Metachronous Metastatic Hormone-sensitive Prostate Cancer Treated with Enzalutamide and Androgen Deprivation Therapy.

Men who initially present with localized prostate cancer and later develop metachronous metastases have a better prognosis than men with de novo metastatic disease and often have a low burden of disease on conventional imaging. Some have disease amenable to metastasis-directed therapy for lymph node or bone metastases, a strategy used by some because no documented overall survival (OS) benefit of combination systemic therapy in this setting. We report data for patients prospectively classified as "M0" at initial diagnosis from the interim analysis of the ENZAMET trial, with 34 mo of median follow-up for survivors.

Testosterone treatment to prevent or revert type 2 diabetes in men enrolled in a lifestyle programme (T4DM): a randomised, double-blind, placebo-controlled, 2-year, phase 3b trial.

Background: Men who are overweight or obese frequently have low serum testosterone concentrations, which are associated with increased risk of type 2 diabetes. We aimed to determine whether testosterone treatment prevents progression to or reverses early type 2 diabetes, beyond the effects of a community-based lifestyle programme.

Methods: T4DM was a randomised, double-blind, placebo-controlled, 2-year, phase 3b trial done at six Australian tertiary care centres.

Return to work following laparoscopic-assisted resection or open resection for rectal cancer: Findings from AlaCaRT-Australasian Laparoscopic Cancer of the Rectum Trial.

Background: Maintaining employment for adults with cancer is important, however, little is known about the impact of surgery for rectal cancer on an individual's capacity to return to work (RTW). This study aimed to determine the impact of laparoscopic vs. open resection on RTW at 12 months.

The effect of lactoferrin supplementation on death or major morbidity in very low birthweight infants (LIFT): a multicentre, double-blind, randomised controlled trial.

Background: Very low birthweight or preterm infants are at increased risk of adverse outcomes including sepsis, necrotising enterocolitis, and death. We assessed whether supplementing the enteral diet of very low-birthweight infants with lactoferrin, an antimicrobial protein, reduces all-cause mortality or major morbidity.

Methods: We did a multicentre, double-blind, pragmatic, randomised superiority trial in 14 Australian and two New Zealand neonatal intensive care units.

SPAR - a randomised, placebo-controlled phase II trial of simvastatin in addition to standard chemotherapy and radiation in preoperative treatment for rectal cancer: an AGITG clinical trial.

Background: Retrospective studies show improved outcomes in colorectal cancer patients if taking statins, including overall survival, pathological response of rectal cancer to preoperative chemoradiotherapy (pCRT), and reduced acute and late toxicities of pelvic radiation. Major tumour regression following pCRT has strong prognostic significance and can be assessed in vivo using MRI-based tumour regression grading (mrTRG) or after surgery using pathological TRG (pathTRG).

Methods: A double-blind phase 2 trial will randomise 222 patients planned to receive long-course fluoropyrimidine-based pCRT for rectal adenocarcinoma at 18+ sites in New Zealand and Australia.

A high-volume, low-cost approach to participant screening and enrolment: Experiences from the T4DM diabetes prevention trial.

Background/aims: Participant recruitment to diabetes prevention randomised controlled trials is challenging and expensive. The T4DM study, a multicentre, Australia-based, Phase IIIb randomised controlled trial of testosterone to prevent Type 2 diabetes in men aged 50-74 years, faced the challenge of screening a large number of prospective participants at a small number of sites, with few staff, and a limited budget for screening activities. This article evaluates a high-volume, low-cost, semi-automated approach to screen and enrol T4DM study participants.

Recruitment of men to a multi-centre diabetes prevention trial: an evaluation of traditional and online promotional strategies.

Background: Effective interventions are required to prevent the current rapid increase in the prevalence of Type 2 diabetes. Clinical trials of large-scale interventions to prevent Type 2 diabetes are essential but recruitment is challenging and expensive, and there are limited data regarding the most cost-effective and efficient approaches to recruitment. This paper aims to evaluate the cost and effectiveness of a range of promotional strategies used to recruit men to a large Type 2 diabetes prevention trial.

Enzalutamide with Standard First-Line Therapy in Metastatic Prostate Cancer.

Background: Enzalutamide, an androgen-receptor inhibitor, has been associated with improved overall survival in men with castration-resistant prostate cancer. It is not known whether adding enzalutamide to testosterone suppression, with or without early docetaxel, will improve survival in men with metastatic, hormone-sensitive prostate cancer.

Methods: In this open-label, randomized, phase 3 trial, we assigned patients to receive testosterone suppression plus either open-label enzalutamide or a standard nonsteroidal antiandrogen therapy (standard-care group).

Telephone call reminders did not increase screening uptake more than SMS reminders: a recruitment study within a trial.

Objectives: The aim of the study was to compare the response rates and costs of phone call vs. short message service (SMS) screening reminders to prospective randomized controlled trial (RCT) participants.

Study Design And Setting: This study was a randomized evaluation within a large Australian diabetes prevention RCT.

Recruitment strategies in randomised controlled trials of men aged 50 years and older: a systematic review.

Objectives: To identify and review evaluations of strategies to recruit men aged 50 years and over to randomised controlled trials (RCTs).

Design: Systematic review and narrative synthesis.

Data Sources: MEDLINE, EMBASE, CINAHL and ORRCA databases were searched to 1 December 2017.

Testosterone therapy to prevent type 2 diabetes mellitus in at-risk men (T4DM): Design and implementation of a double-blind randomized controlled trial.

Background: Low circulating testosterone is associated with an increased risk of developing type 2 diabetes (T2DM) in overweight men with impaired glucose tolerance (IGT).

Aims: To determine in a multi-centre, double-blinded placebo-controlled randomized trial whether testosterone treatment combined with lifestyle intervention (Weight Watchers) relative to lifestyle intervention alone reduces T2DM incidence and improves glucose tolerance at 2 years.

Study Population: Overweight or obese men aged 50-74 years with a serum testosterone of ≤14 nmol/L and IGT or newly diagnosed T2DM established by an oral glucose tolerance test (OGTT).

Disease-free Survival and Local Recurrence After Laparoscopic-assisted Resection or Open Resection for Rectal Cancer: The Australasian Laparoscopic Cancer of the Rectum Randomized Clinical Trial.

Objective: The aim of the study was to determine the efficacy of laparoscopic rectal resection (Lap) versus open laparotomy and rectal resection (Open) for rectal cancer on locoregional recurrence (LRR) and disease-free survival (DFS) at 2 years.

Summary Background Data: Although a Lap approach to colon cancer surgery may offer similar oncological outcomes to Open with potentially less morbidity, this remains to be clearly established for the treatment of rectal cancer.

Methods: A randomized, multicenter noninferiority phase 3 trial of 475 patients with T1 to T3 rectal adenocarcinoma <15 cm from anal verge, given Lap or Open and followed for a minimum 2 years to assess LRR, DFS, and overall survival (OS).

Cancer Molecular Screening and Therapeutics (MoST): a framework for multiple, parallel signal-seeking studies of targeted therapies for rare and neglected cancers.

Background: Precision medicine aims to link molecular targets in tumours with corresponding therapies, particularly for patients with rare cancers. Innovative approaches are needed to translate molecular opportunities into clinical care. The Cancer Molecular Screening and Therapeutics (MoST) program employs a molecular screening platform to identify molecular changes of therapeutic relevance (actionable changes) and a master protocol for multiple, parallel signal-seeking clinical substudies, focused on therapies for patients with rare and neglected cancers.

D-Dimer Predicts Long-Term Cause-Specific Mortality, Cardiovascular Events, and Cancer in Patients With Stable Coronary Heart Disease: LIPID Study.

Background: D-dimer, a degradation product of cross-linked fibrin, is a marker for hypercoagulability and thrombotic events. Moderately elevated levels of D-dimer are associated with the risk of venous and arterial events in patients with vascular disease. We assessed the role of D-dimer levels in predicting long-term vascular outcomes, cause-specific mortality, and new cancers in the LIPID trial (Long-Term Intervention with Pravastatin in Ischaemic Disease) in the context of other risk factors.

Delayed versus Immediate Cord Clamping in Preterm Infants.

Background: The preferred timing of umbilical-cord clamping in preterm infants is unclear.

Methods: We randomly assigned fetuses from women who were expected to deliver before 30 weeks of gestation to either immediate clamping of the umbilical cord (≤10 seconds after delivery) or delayed clamping (≥60 seconds after delivery). The primary composite outcome was death or major morbidity (defined as severe brain injury on postnatal ultrasonography, severe retinopathy of prematurity, necrotizing enterocolitis, or late-onset sepsis) by 36 weeks of postmenstrual age.

Long-Term Effectiveness and Safety of Pravastatin in Patients With Coronary Heart Disease: Sixteen Years of Follow-Up of the LIPID Study.

Background: We aimed to assess the long-term effects of treatment with statin therapy on all-cause mortality, cause-specific mortality, and cancer incidence from extended follow-up of the Long-term Intervention with Pravastatin in Ischemic Disease (LIPID) trial.

Methods And Results: LIPID initially compared pravastatin and placebo over 6 years in 9014 patients with previous coronary heart disease. After the double-blind period, all patients were offered open-label statin therapy.