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

Psychological impact of referral to an oncology hospital on patients with an ovarian mass

OBJECTIVES: In patients with an ovarian mass, a risk of malignancy assessment is used to decide whether referral to an oncology hospital is indicated. Risk assessment strategies do not perform optimally, resulting in either referral of patients with a benign mass or patients with a malignant mass not being referred. This process may affect the psychological well-being of patients. We evaluated cancer-specific distress during work-up for an ovarian mass, and patients' perceptions during work-up, referral, and treatment. METHODS: Patients with an ovarian mass scheduled for surgery were enrolled. Using questionnaires we measured (1) cancer-specific distress using the cancer worry scale, (2) patients' preferences regarding referral (evaluated pre-operatively), and (3) patients' experiences with work-up and treatment (evaluated post-operatively). A cancer worry scale score of ≥14 was considered as clinically significant cancer-specific distress. RESULTS: A total of 417 patients were included, of whom 220 (53%) were treated at a general hospital and 197 (47%) at an oncology hospital. Overall, 57% had a cancer worry scale score of ≥14 and this was higher in referred patients (69%) than in patients treated at a general hospital (43%). 53% of the patients stated that the cancer risk should not be higher than 25% to undergo surgery at a general hospital. 96% of all patients were satisfied with the overall work-up and treatment. No difference in satisfaction was observed between patients correctly (not) referred and patients incorrectly (not) referred. CONCLUSIONS: Relatively many patients with an ovarian mass experienced high cancer-specific distress during work-up. Nevertheless, patients were satisfied with the treatment, regardless of the final diagnosis and the location of treatment. Moreover, patients preferred to be referred even if there was only a relatively low probability of having ovarian cancer. Patients' preferences should be taken into account when deciding on optimal cut-offs for risk assessment strategies

Psychological impact of referral to an oncology hospital on patients with an ovarian mass

Objectives In patients with an ovarian mass, a risk of malignancy assessment is used to decide whether referral to an oncology hospital is indicated. Risk assessment strategies do not perform optimally, resulting in either referral of patients with a benign mass or patients with a malignant mass not being referred. This process may affect the psychological well-being of patients. We evaluated cancer-specific distress during work-up for an ovarian mass, and patients' perceptions during work-up, referral, and treatment. Methods Patients with an ovarian mass scheduled for surgery were enrolled. Using questionnaires we measured (1) cancer-specific distress using the cancer worry scale, (2) patients' preferences regarding referral (evaluated pre-operatively), and (3) patients' experiences with work-up and treatment (evaluated post-operatively). A cancer worry scale score of ≥14 was considered as clinically significant cancer-specific distress. Results A total of 417 patients were included, of whom 220 (53%) were treated at a general hospital and 197 (47%) at an oncology hospital. Overall, 57% had a cancer worry scale score of ≥14 and this was higher in referred patients (69%) than in patients treated at a general hospital (43%). 53% of the patients stated that the cancer risk should not be higher than 25% to undergo surgery at a general hospital. 96% of all patients were satisfied with the overall work-up and treatment. No difference in satisfaction was observed between patients correctly (not) referred and patients incorrectly (not) referred. Conclusions Relatively many patients with an ovarian mass experienced high cancer-specific distress during work-up. Nevertheless, patients were satisfied with the treatment, regardless of the final diagnosis and the location of treatment. Moreover, patients preferred to be referred even if there was only a relatively low probability of having ovarian cancer. Patients' preferences should be taken into account when deciding on optimal cut-offs for risk assessment strategies

Continuous glucose monitoring during diabetic pregnancy (GlucoMOMS): A multicentre randomized controlled trial

Aim: Diabetes is associated with a high risk of adverse pregnancy outcomes. Optimal glycaemic control is fundamental and is traditionally monitored with self-measured glucose profiles and periodic HbA1c measurements. We investigated the effectiveness of additional use of retrospective continuous glucose monitoring (CGM) in diabetic pregnancies. Material and methods: We performed a nationwide multicentre, open label, randomized, controlled trial to study pregnant women with type 1 or type 2 diabetes who were undergoing insulin therapy at gestational age < 16 weeks, or women who were undergoing insulin treatment for gestational diabetes at gestational age < 30 weeks. Women were randomly allocated (1:1) to intermittent use of retrospective CGM or to standard treatment. Glycaemic control was assessed by CGM for 5-7 days every 6 weeks in the CGM group, while self-monitoring of blood glucose and HbA1c measurements were applied in both groups. Primary outcome was macrosomia, defined as birth weight above the 90th percentile. Secondary outcomes were glycaemic control and maternal and neonatal complications. Results: Between July 2011 and September 2015, we randomized 300 pregnant women with type 1 (n = 109), type 2 (n = 82) or with gestational (n = 109) diabetes to either CGM (n = 147) or standard treatment (n = 153). The incidence of macrosomia was 31.0% in the CGM group and 28.4% in the standard treatment group (relative risk [RR], 1.06; 95% CI, 0.83-1.37). HbA1c levels were similar between treatment groups. Conclusions: In diabetic pregnancy, use of intermittent retrospective CGM did not reduce the risk of macrosomia. CGM provides detailed information concerning glycaemic fluctuations but, as a treatment strategy, does not translate into improved pregnancy outcome

A multi-centre, non-inferiority, randomised controlled trial to compare a cervical pessary with a cervical cerclage in the prevention of preterm delivery in women with short cervical length and a history of preterm birth - PC study

Background Preterm birth is in quantity and in severity the most important contributor of perinatal morbidity and mortality both in well- and low-resource countries. Cervical pessary and cervical cerclage are both considered as preventive treatments in women at risk for preterm birth. We aim to evaluate whether a cervical pessary can replace cervical cerclage for preventing recurrent preterm birth in women with a prior preterm birth due to cervical insufficiency or in women with a prior preterm birth and a short cervix in the current pregnancy. Methods/design A nationwide open-label multicentre randomised clinical trial will be set up to study women with a singleton pregnancy and a prior preterm birth before 34 weeks of gestation. Women are eligible in case of previous preterm birth based on cervical insufficiency (primary intervention, <16 weeks) or in case of previous preterm birth and a short cervical length in current pregnancy ≤25 mm (secondary intervention, <24 weeks). Eligible women will be randomised to either cervical pessary or cervical cerclage. Both interventions will be removed at labour or at 36 weeks of gestational age, whatever comes first. The primary outcome will be delivery before 32 weeks. Secondary outcomes will be gestational age at birth, preterm birth rate before 24, 28, 34 and 37 weeks of gestation (overall and stratified by spontaneous or indicated delivery), premature rupture of membranes, use of tocolysis and/or corticosteroids during pregnancy, mode of delivery, maternal infections, maternal side effects, neonatal and maternal hospital admissions, and a composite of adverse perinatal outcomes including both morbidity and mortality. We assume an event rate of 20% preterm birth before 32 weeks for cerclage and use a non-inferiority margin of 10% for the cervical pessary. Using an alpha of 0.05 and power of 0.80 we need 2 groups of 200 women each. Discussion The outcome of this study will indicate the effectiveness and the cost-effectiveness of a cervical cerclage and of a cervical pessary

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