Efficacy and Safety of Insulin Aspart vs. Human Insulin During Pregnancy by Women With Type 1 Diabetes

A Randomised, Parallel-group, Open-label, Multinational Trial Comparing the Safety and Efficacy of Insulin Aspart (NovoRapid®) Versus Human Insulin (Actrapid®), Used in a Multiple Injection Regimen, in the Treatment of Pregnant Women With Type 1 Diabetes, Focusing on Maternal Hypoglycaemia and Pregnancy Outcomes

This trial was conducted in Europe, Middle East, North America and South America.

The aim of this trial was to compare the use of an intensified insulin treatment with insulin aspart (NovoRapid®) versus human insulin (Actrapid®) in pregnancy.

Study Overview

• Status: Completed
• Conditions: Diabetes; Diabetes Mellitus, Type 1
• Intervention / Treatment: Drug: insulin aspart; Drug: human insulin

• Study Type: Interventional
• Enrollment (Actual): 419
• Phase: Phase 4

Contacts and Locations

Study Locations

• Argentina
  • Ciudad de Buenos Aires, Argentina, 1405
    • Novo Nordisk Investigational Site
  • Pcia de Cordoba, Argentina, 5000
    • Novo Nordisk Investigational Site
• Austria
  • Graz, Austria, 8036
    • Novo Nordisk Investigational Site
  • Salzburg, Austria, 5020
    • Novo Nordisk Investigational Site
  • Wien, Austria, 1090
    • Novo Nordisk Investigational Site
  • Wien, Austria, A-1130
    • Novo Nordisk Investigational Site
• Bulgaria
  • Sofia, Bulgaria, 1431
    • Novo Nordisk Investigational Site
• Canada
  • Ottawa, Canada, K1H 8L6
    • Novo Nordisk Investigational Site
  • St John's, Canada, A1B 3V6
    • Novo Nordisk Investigational Site
  • Toronto, Canada, M5G 1X5
    • Novo Nordisk Investigational Site
  • Toronto, Canada, M5S 1B2
    • Novo Nordisk Investigational Site
  • Vancouver, Canada, V5Z 1C6
    • Novo Nordisk Investigational Site
  • Winnipeg, Canada, R3C 0N2
    • Novo Nordisk Investigational Site
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 1V7
      • Novo Nordisk Investigational Site
• Croatia
  • Zagreb, Croatia, 10 000
    • Novo Nordisk Investigational Site
• Denmark
  • Hvidovre, Denmark, 2650
    • Novo Nordisk Investigational Site
  • København ø, Denmark, 2100
    • Novo Nordisk Investigational Site
• Finland
  • Helsinki, Finland, 00029
    • Novo Nordisk Investigational Site
  • Kuopio, Finland, 70210
    • Novo Nordisk Investigational Site
  • Oulu, Finland, 90029
    • Novo Nordisk Investigational Site
• France
  • ANGERS cedex 09, France, 49033
    • Novo Nordisk Investigational Site
  • Avignon, France, 84902
    • Novo Nordisk Investigational Site
  • Bondy, France, 93143
    • Novo Nordisk Investigational Site
  • Brest, France, 29609
    • Novo Nordisk Investigational Site
  • Lille, France, 59037
    • Novo Nordisk Investigational Site
  • MARSEILLE Cédex 05, France, 13385
    • Novo Nordisk Investigational Site
  • Nantes, France, 44093
    • Novo Nordisk Investigational Site
  • Nimes, France, 30006
    • Novo Nordisk Investigational Site
  • Paris, France, 75181
    • Novo Nordisk Investigational Site
  • PuyRicard, France, 13540
    • Novo Nordisk Investigational Site
  • Strasbourg, France, 67000
    • Novo Nordisk Investigational Site
  • Strasbourg, France, 67091
    • Novo Nordisk Investigational Site
  • TOULOUSE cedex, France, 31054
    • Novo Nordisk Investigational Site
  • Valenciennes, France, 59322
    • Novo Nordisk Investigational Site
• Germany
  • Berlin, Germany, 12051
    • Novo Nordisk Investigational Site
• Greece
  • Athens, Greece, GR-11528
    • Novo Nordisk Investigational Site
  • Athens, Greece, 11521
    • Novo Nordisk Investigational Site
  • Athens, Greece, 151 23
    • Novo Nordisk Investigational Site
• Ireland
  • Dublin, Ireland, DUBLIN 7
    • Novo Nordisk Investigational Site
• Israel
  • Beer Sheva, Israel, 84101
    • Novo Nordisk Investigational Site
  • Haifa, Israel, 31096
    • Novo Nordisk Investigational Site
  • Jerusalem, Israel, 91031
    • Novo Nordisk Investigational Site
  • Petah-Tikva, Israel, 49100
    • Novo Nordisk Investigational Site
• Netherlands
  • Apeldoorn, Netherlands, 7334 DZ
    • Novo Nordisk Investigational Site
  • Brunssum, Netherlands, 6442 BE
    • Novo Nordisk Investigational Site
  • Den Haag, Netherlands, 2597 AX
    • Novo Nordisk Investigational Site
  • Eindhoven, Netherlands, 5631 BM
    • Novo Nordisk Investigational Site
  • Roermond, Netherlands, 6043 CV
    • Novo Nordisk Investigational Site
  • Rotterdam, Netherlands, 3045 PM
    • Novo Nordisk Investigational Site
  • Utrecht, Netherlands, 3584 CX
    • Novo Nordisk Investigational Site
• Norway
  • Oslo, Norway, 0027
    • Novo Nordisk Investigational Site
  • Tromsø, Norway, 9038
    • Novo Nordisk Investigational Site
  • Trondheim, Norway, NO-7030
    • Novo Nordisk Investigational Site
• Poland
  • Krakow, Poland, 31-501
    • Novo Nordisk Investigational Site
  • Lodz, Poland, 93-338
    • Novo Nordisk Investigational Site
  • Lublin, Poland, 20-081
    • Novo Nordisk Investigational Site
  • Olsztyn, Poland, 10-457
    • Novo Nordisk Investigational Site
  • Poznan, Poland, 60-535
    • Novo Nordisk Investigational Site
  • Szczecin, Poland, 71-455
    • Novo Nordisk Investigational Site
  • Warszawa, Poland, 02-097
    • Novo Nordisk Investigational Site
  • Wroclaw, Poland, 50-306
    • Novo Nordisk Investigational Site
• Russian Federation
  • Moscow, Russian Federation, 101000
    • Novo Nordisk Investigational Site
  • Moscow, Russian Federation, 127411
    • Novo Nordisk Investigational Site
  • Saint-Petersburg, Russian Federation, 199034
    • Novo Nordisk Investigational Site
• Spain
  • Alicante, Spain, 03010
    • Novo Nordisk Investigational Site
  • Girona, Spain, 17007
    • Novo Nordisk Investigational Site
  • Santander, Spain, 39008
    • Novo Nordisk Investigational Site
  • Sevilla, Spain, 41014
    • Novo Nordisk Investigational Site
• United Kingdom
  • Ashington, United Kingdom, NE63 9JJ
    • Novo Nordisk Investigational Site
  • Bath, United Kingdom, BA1 3NG
    • Novo Nordisk Investigational Site
  • Belfast, United Kingdom, BT12 6BA
    • Novo Nordisk Investigational Site
  • Birmingham, United Kingdom, B9 5SS
    • Novo Nordisk Investigational Site
  • Bristol, United Kingdom, BS10 5NB
    • Novo Nordisk Investigational Site
  • Cambridge, United Kingdom, CB2 2QQ
    • Novo Nordisk Investigational Site
  • Edgbaston, Birmingham, United Kingdom, B15 2TH
    • Novo Nordisk Investigational Site
  • Edinburgh, United Kingdom, EH16 4SA
    • Novo Nordisk Investigational Site
  • Exeter, United Kingdom, EX2 5AX
    • Novo Nordisk Investigational Site
  • Hull, United Kingdom, HU3 2JZ
    • Novo Nordisk Investigational Site
  • Leeds, United Kingdom, LS9 7TF
    • Novo Nordisk Investigational Site
  • Leicester, United Kingdom, LE1 5WW
    • Novo Nordisk Investigational Site
  • Liverpool, United Kingdom, L7 8XP
    • Novo Nordisk Investigational Site
  • London, United Kingdom, SE5 9RS
    • Novo Nordisk Investigational Site
  • London, United Kingdom, W12 OHS
    • Novo Nordisk Investigational Site
  • Newcastle, United Kingdom, NE29 0LR
    • Novo Nordisk Investigational Site
  • Norfolk, United Kingdom, NR4 7UY
    • Novo Nordisk Investigational Site
  • Northampton, United Kingdom, NN1 5BD
    • Novo Nordisk Investigational Site
  • Nottingham, United Kingdom, NG7 2UH
    • Novo Nordisk Investigational Site
  • Oxford, United Kingdom, OX3 9DU
    • Novo Nordisk Investigational Site
  • Plymouth, United Kingdom, PL8 8DQ
    • Novo Nordisk Investigational Site
  • Reading, United Kingdom, RG51 5BS
    • Novo Nordisk Investigational Site
  • Sheffield, United Kingdom, S5 7AU
    • Novo Nordisk Investigational Site
  • Sheffield, United Kingdom, S10 2JF
    • Novo Nordisk Investigational Site
  • Southampton, United Kingdom, SO16 6YD
    • Novo Nordisk Investigational Site
  • Stourbridge, United Kingdom, DY3 3BG
    • Novo Nordisk Investigational Site
  • Worcester, United Kingdom, WR5 1HN
    • Novo Nordisk Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Type 1 diabetes
• Treated with insulin for at least 12 months
• Either plan to become pregnant in the immediate future, willing to undertake pre pregnancy counselling, and has a screening HbA1c lesser than or equal to 12.0%, or
• Pregnant with normal singleton pregnancy, gestational age for at least 10 weeks at the time of randomisation, confirmed by ultrasound scan.

Exclusion Criteria:

• Previous birth of child with a major congenital malformation
• More than 2 previous multiple miscarriages or stillbirths
• Severe hyperemesis gravidarum, requiring hospitalisation, according to Investigator judgement
• Subjects being treated for infertility
• Proliferative retinopathy or maculopathy requiring acute treatment
• Drug or alcohol abuse
• Impaired renal, hepatic or cardiac function

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Relative risk of major maternal hypoglycaemia	after 24 hours

Secondary Outcome Measures

Outcome Measure
Relative risk of major and minor hypoglycaemia
Diabetic complications
Obstetric complications
Other Adverse Events

Collaborators and Investigators

• Sponsor: Novo Nordisk A/S
• Investigators: Study Director: Global Clinical Registry (1452, GCR), Novo Nordisk A/S

Publications and helpful links

General Publications

• Mathiesen ER, Kinsley B, Amiel SA, Heller S, McCance D, Duran S, Bellaire S, Raben A; Insulin Aspart Pregnancy Study Group. Maternal glycemic control and hypoglycemia in type 1 diabetic pregnancy: a randomized trial of insulin aspart versus human insulin in 322 pregnant women. Diabetes Care. 2007 Apr;30(4):771-6. doi: 10.2337/dc06-1887.
• Hod M, Jovanovic L. Improving outcomes in pregnant women with type 1 diabetes. Diabetes Care. 2007 Jul;30(7):e62. doi: 10.2337/dc07-0488. No abstract available.
• Hod M, Damm P, Kaaja R, Visser GH, Dunne F, Demidova I, Hansen AS, Mersebach H; Insulin Aspart Pregnancy Study Group. Fetal and perinatal outcomes in type 1 diabetes pregnancy: a randomized study comparing insulin aspart with human insulin in 322 subjects. Am J Obstet Gynecol. 2008 Feb;198(2):186.e1-7. doi: 10.1016/j.ajog.2007.08.005. Epub 2007 Oct 1.
• McCance DR, Damm P, Mathiesen ER, Hod M, Kaaja R, Dunne F, Jensen LE, Mersebach H. Evaluation of insulin antibodies and placental transfer of insulin aspart in pregnant women with type 1 diabetes mellitus. Diabetologia. 2008 Nov;51(11):2141-3. doi: 10.1007/s00125-008-1120-y. Epub 2008 Aug 23. No abstract available.
• Heller S, Damm P, Mersebach H, Skjoth TV, Kaaja R, Hod M, Duran-Garcia S, McCance D, Mathiesen ER. Hypoglycemia in type 1 diabetic pregnancy: role of preconception insulin aspart treatment in a randomized study. Diabetes Care. 2010 Mar;33(3):473-7. doi: 10.2337/dc09-1605. Epub 2009 Dec 10.
• Damm P, Mersebach H, Rastam J, Kaaja R, Hod M, McCance DR, Mathiesen ER. Poor pregnancy outcome in women with type 1 diabetes is predicted by elevated HbA1c and spikes of high glucose values in the third trimester. J Matern Fetal Neonatal Med. 2014 Jan;27(2):149-54. doi: 10.3109/14767058.2013.806896. Epub 2013 Jun 20.
• Altschuler JA, Casella SJ, MacKenzie TA, Curtis KM. The effect of cinnamon on A1C among adolescents with type 1 diabetes. Diabetes Care. 2007 Apr;30(4):813-6. doi: 10.2337/dc06-1871.
• Williams MM, Clouse RE, Nix BD, Rubin EH, Sayuk GS, McGill JB, Gelenberg AJ, Ciechanowski PS, Hirsch IB, Lustman PJ. Efficacy of sertraline in prevention of depression recurrence in older versus younger adults with diabetes. Diabetes Care. 2007 Apr;30(4):801-6. doi: 10.2337/dc06-1825.

Helpful Links

• Clinical Trials at Novo Nordisk

Study record dates

Study Major Dates

• Study Start: September 1, 2002
• Primary Completion (Actual): April 1, 2005
• Study Completion (Actual): April 1, 2005

Study Registration Dates

• First Submitted: August 10, 2006
• First Submitted That Met QC Criteria: August 16, 2006
• First Posted (Estimate): August 17, 2006

Study Record Updates

• Last Update Posted (Estimate): December 21, 2016
• Last Update Submitted That Met QC Criteria: December 20, 2016
• Last Verified: December 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 1; Hypoglycemic Agents; Physiological Effects of Drugs; Insulin; Insulin, Globin Zinc; Insulin Aspart
• Other Study ID Numbers: ANA-1474