A prospective randomised cross-over study of the effect of insulin analogues and human insulin on the frequency of severe hypoglycaemia in patients with type 1 diabetes and recurrent hypoglycaemia (the HypoAna trial): study rationale and design.
BACKGROUND
Severe hypoglycaemia still represents a significant problem in insulin-treated diabetes. Most patients do not experience severe hypoglycaemia often. However, 20% of patients with type 1 diabetes experience recurrent severe hypoglycaemia corresponding to at least two episodes per year. The effect of insulin analogues on glycaemic control has been documented in large trials, while their effect on the frequency of severe hypoglycaemia is less clear, especially in patients with recurrent severe hypoglycaemia. The HypoAna Trial is designed to investigate whether short-acting and long-acting insulin analogues in comparison with human insulin are superior in reducing the occurrence of severe hypoglycaemic episodes in patients with recurrent hypoglycaemia. This paper reports the study design of the HypoAna Trial.


METHODS
The study is a Danish two-year investigator-initiated, prospective, randomised, open, blinded endpoint (PROBE), multicentre, cross-over trial investigating the effect of insulin analogues versus human insulin on the frequency of severe hypoglycaemia in subjects with type 1 diabetes. Patients are randomised to treatment with basal-bolus therapy with insulin detemir / insulin aspart or human NPH insulin / human regular insulin in random order. The major inclusion criterion is history of two or more episodes of severe hypoglycaemia in the preceding year.


CONCLUSIONS
In contrast to almost all other studies in this field the HypoAna Trial includes only patients with major problems with hypoglycaemia. The HypoAna Trial will elucidate whether basal-bolus regimen with short-acting and long-acting insulin analogues in comparison with human insulin are superior in reducing occurrence of severe hypoglycaemic episodes in hypoglycaemia prone patients with type 1 diabetes. http://www.clinicaltrials.gov: NCT00346996.
Department of Cardiology, Nephrology and Endocrinology, Hillerød University Hospital, Dyrehavevej 29, DK-3400, Hillerød, Denmark. pelk@hih.regionh.dk.
Peter Lommer
PL
Kristensen
Ulrik
U
Pedersen-Bjergaard
Henning
H
Beck-Nielsen
Kirsten
K
Nørgaard
Hans
H
Perrild
Jens Sandahl
JS
Christiansen
Tonny
T
Jensen
Hans-Henrik
HH
Parving
Birger
B
Thorsteinsson
Lise
L
Tarnow