SUGAR-DIP trial: Oral medication strategy versus insulin for diabetes in pregnancy, study protocol for a multicentre, open-label, non-inferiority, randomised controlled trial

Introduction In women with gestational diabetes mellitus (GDM) requiring pharmacotherapy, insulin was the established first-line treatment. More recently, oral glucose lowering drugs (OGLDs) have gained popularity as a patient-friendly, less expensive and safe alternative. Monotherapy with metformin or glibenclamide (glyburide) is incorporated in several international guidelines. In women who do not reach sufficient glucose control with OGLD monotherapy, usually insulin is added, either with or without continuation of OGLDs. No reliable data from clinical trials, however, are available on the effectiveness of a treatment strategy using all three agents, metformin, glibenclamide and insulin, in a stepwise approach, compared with insulin-only therapy for improving pregnancy outcomes. In this trial, we aim to assess the clinical effectiveness, cost-effectiveness and patient experience of a stepwise combined OGLD treatment protocol, compared with conventional insulin-based therapy for GDM. Methods The SUGAR-DIP trial is an open-label, multicentre randomised controlled non-inferiority trial. Participants are women with GDM who do not reach target glycaemic control with modification of diet, between 16 and 34 weeks of gestation. Participants will be randomised to either treatment with OGLDs, starting with metformin and supplemented as needed with glibenclamide, or randomised to treatment with insulin. In women who do not reach target glycaemic control with combined metformin and glibenclamide, glibenclamide will be substituted with insulin, while continuing metformin. The primary outcome will be the incidence of large-for-gestational-age infants (birth weight >90th percentile). Secondary outcome measures are maternal diabetes-related endpoints, obstetric complications, neonatal complications and cost-effectiveness analysis. Outcomes will be analysed according to the intention-to-treat principle. Ethics and dissemination The study protocol was approved by the Ethics Committee of the Utrecht University Medical Centre. Approval by the boards of management for all participating hospitals will be obtained. Trial results will be submitted for publication in peer-reviewed journals

Empirical management of community-acquired pneumonia: impact of concurrent A/H1N1 influenza pandemic on guideline implementation

Background: Guideline-concordant therapies have been proven to be associated with improved health and economic outcomes in the treatment of community-acquired pneumonia (CAP). However, actual use of CAP guidelines remains poor, but using tailored interventions looks promising. Based on local observations, we assessed the impact of low-intensity interventions to improve guideline use. Methods: Pre- and post-intervention study with segmented regression analysis in a large tertiary care centre [University Hospitals Leuven (UZL)] and a smaller secondary care control hospital [Ziekenhuis Oost-Limburg (ZOL)] from October 2007 through to June 2010 in Belgium. Results: A total of 477 patients were included in UZL, with 58.5% of the patients treated according to local guidelines. Guideline adherence remained stable, but a decrease (-28.6%; P=0.021) was observed during guideline re-introduction in October 2009. Further analysis showed a high correlation with the concurrent A/H1N1 influenza pandemic (r(point-biserial)=0.683; P=0.045) and with suspected influenza infection (odds ratio=2.70; P=0.038). In ZOL, 326 patients were enrolled, with 69.3% being treated concordantly. A similar, non-significant decrease in guideline adherence was observed after October 2009. Conclusions: Our interventions did not lead to a higher proportion of CAP patients receiving guideline-compliant therapy. Instead, a compliance decrease was observed, coinciding with the peak in the A/H1N1 pandemic in the population. Similar observations could be made in ZOL. The widespread attention for this pandemic may have altered the perception of needed antibiotic therapy for pulmonary infections, bypassing our interventions and decreasing actual guideline compliance. Increased vigilance and follow-up is needed when epidemics with similar impact occur in the future

SUGAR-DIP trial:Oral medication strategy versus insulin for diabetes in pregnancy, study protocol for a multicentre, open-label, non-inferiority, randomised controlled trial

Introduction In women with gestational diabetes mellitus (GDM) requiring pharmacotherapy, insulin was the established first-line treatment. More recently, oral glucose lowering drugs (OGLDs) have gained popularity as a patient-friendly, less expensive and safe alternative. Monotherapy with metformin or glibenclamide (glyburide) is incorporated in several international guidelines. In women who do not reach sufficient glucose control with OGLD monotherapy, usually insulin is added, either with or without continuation of OGLDs. No reliable data from clinical trials, however, are available on the effectiveness of a treatment strategy using all three agents, metformin, glibenclamide and insulin, in a stepwise approach, compared with insulin-only therapy for improving pregnancy outcomes. In this trial, we aim to assess the clinical effectiveness, cost-effectiveness and patient experience of a stepwise combined OGLD treatment protocol, compared with conventional insulin-based therapy for GDM. Methods The SUGAR-DIP trial is an open-label, multicentre randomised controlled non-inferiority trial. Participants are women with GDM who do not reach target glycaemic control with modification of diet, between 16 and 34 weeks of gestation. Participants will be randomised to either treatment with OGLDs, starting with metformin and supplemented as needed with glibenclamide, or randomised to treatment with insulin. In women who do not reach target glycaemic control with combined metformin and glibenclamide, glibenclamide will be substituted with insulin, while continuing metformin. The primary outcome will be the incidence of large-for-gestational-age infants (birth weight >90th percentile). Secondary outcome measures are maternal diabetes-related endpoints, obstetric complications, neonatal complications and cost-effectiveness analysis. Outcomes will be analysed according to the intention-to-treat principle. Ethics and dissemination The study protocol was approved by the Ethics Committee of the Utrecht University Medical Centre. Approval by the boards of management for all participating hospitals will be obtained. Trial results will be submitted for publication in peer-reviewed journals