Comparison of Optimised MDI versus Pumps with or without Sensors in Severe Hypoglycaemia (the Hypo COMPaSS trial)

Abstract

BackgroundSevere hypoglycaemia (SH) is one of the most feared complications of type 1 diabetes (T1DM) with a reported prevalence of nearly 40%. In randomized trials of Multiple Daily Injections (MDI) and Continuous Subcutaneous Insulin Infusion (CSII) therapy there is a possible benefit of CSII in reducing SH. However few trials have used basal insulin analogues as the basal insulin in the MDI group and individuals with established SH have often been excluded from prospective studies. In published studies investigating the effect of Real Time Continuous Glucose Monitoring (RT-CGM) benefit in terms of reduced SH has not yet been demonstrated. The primary objective of this study is to elucidate whether in people with T1DM complicated by impaired awareness of hypoglycaemia (IAH), rigorous prevention of biochemical hypoglycaemia using optimized existing self-management technology and educational support will restore awareness and reduce risk of recurrent SH.Methods/designThis is a multicentre prospective RCT comparing hypoglycaemia avoidance with optimized MDI and CSII with or without RT-CGM in a 2×2 factorial design in people with type 1 diabetes who have IAH. The primary outcome measure for this study is the difference in IAH (Gold score) at 24 weeks. Secondary outcomes include biomedical measures such as HbA1c, SH incidence, blinded CGM analysis, self monitored blood glucose (SMBG) and response to hypoglycaemia in gold standard clamp studies. Psychosocial measures including well-being and quality of life will also be assessed using several validated and novel measures. Analysis will be on an intention-to-treat basis.DiscussionMost existing RCTs using this study’s interventions have been powered for change in HbA1c rather than IAH or SH. This trial will demonstrate whether IAH can be reversed and SH prevented in people with T1DM in even those at highest risk by using optimized conventional management and existing technology.Trial RegistrationISRCTN52164803 Eudract No: 2009-015396-27

Recovery of Hypoglycemia Awareness in Long-standing Type 1 Diabetes: A Multicenter 2 × 2 Factorial Randomized Controlled Trial Comparing Insulin Pump With Multiple Daily Injections and Continuous With Conventional Glucose Self-monitoring (HypoCOMPaSS)

“…The full study protocol is published (21) and accessible online (http://www.ncl .ac.uk/nctu/assets/documents/hypo COMPASS%20Protocol%20version% 203.1%20-%2026%20Apr%202012.pdf).…”

“…Full eligibility criteria are detailed in the study protocol (21 Stratification by HbA 1c was included to minimize selection bias, as it was hypothesized that two subgroups may not respond to the trial intervention and achieve improved hypoglycemia awareness or reduction in SH: those with a strong psychobehavioral drive to avoid high glucose even if this leads to recurrent biochemical hypoglycemia (characterized by lower HbA 1c ); and those with severe autonomic dysfunction precluding satisfactory restoration of awareness despite effective biochemical hypoglycemia avoidance (characterized by suboptimal HbA 1c ).…”

“…To improve sensitivity to change over a short period, we used also the Hypoglycemia Awareness Questionnaire (HypoA-Q), recently validated outside the current study (23). Screening was undertaken for undiagnosed thyroid, Addison, and celiac disease (21).…”

“…Following randomization, the number of study visits was the same for all participants, tailored for each group to technical aspects of their insulin administration and glucose monitoring intervention (21). All participants, whether allocated aspart insulin delivery by CSII (Paradigm Veo insulin pump; Medtronic) or MDIs (aspart/glargine) were given an insulin pump enabling benefit from direct transmission of SMBG levels to bolus calculator.…”

“…All participants were given identical written guidance on insulin titration primarily targeted toward absolute avoidance of biochemical hypoglycemia (21). Glargine was administered before bed with addition of a second dose before breakfast in those with consistent glucose .7.0 mmol/L before the evening meal or highly variable glucose levels between breakfast and the evening meal.…”