Efficacy and Safety of Insulin Detemir Versus Neutral Protamine Hagedorn (NPH) Insulin in Pregnant Women With Type 1 Diabetes

A Randomised, Parallel-group, Open-labelled, Multinational Trial Comparing the Efficacy and Safety of Insulin Detemir (Levemir®) Versus Human Insulin (NPH Insulin), Used in Combination With Insulin Aspart as Bolus Insulin, in the Treatment of Pregnant Women With Type 1 Diabetes

This trial is conducted in Africa, Europe, North and South America and Oceania. The aim of this trial is to compare the effect and safety on blood glucose control in pregnant women with type 1 diabetes of a modern insulin analogue (insulin detemir) and human insulin (NPH insulin) given as long-acting insulin in combination with a short-acting insulin (insulin aspart).

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 470
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1181ACH
    • Novo Nordisk Investigational Site
  • Buenos Aires, Argentina, B1704ETD
    • Novo Nordisk Investigational Site
  • Buenos Aires, Argentina, C1155ADP
    • Novo Nordisk Investigational Site
  • Buenos Aires, Argentina, C1246ABQ
    • Novo Nordisk Investigational Site
  • Mar del Plata, Argentina, B7602CBM
    • Novo Nordisk Investigational Site
  • Pcia de Cordoba, Argentina, 5000
    • Novo Nordisk Investigational Site
  • Salta, Argentina, A4406CLA
    • Novo Nordisk Investigational Site
• Australia
  • Clayton, Australia, 3168
    • Novo Nordisk Investigational Site
  • Garran, Australia, 2605
    • Novo Nordisk Investigational Site
  • South Brisbane, Australia, 4101
    • Novo Nordisk Investigational Site
  • Subiaco, Australia, 6008
    • Novo Nordisk Investigational Site
  • Wollongong, Australia, 2500
    • Novo Nordisk Investigational Site
  • New South Wales
    • Broadmeadow, New South Wales, Australia, 2292
      • Novo Nordisk Investigational Site
    • Camperdown, New South Wales, Australia, 2050
      • Novo Nordisk Investigational Site
    • St Leonards, New South Wales, Australia, 2065
      • Novo Nordisk Investigational Site
  • South Australia
    • Elizabeth Vale, South Australia, Australia, 5112
      • Novo Nordisk Investigational Site
• Austria
  • Feldkirch, Austria, 6807
    • Novo Nordisk Investigational Site
  • Innsbruck, Austria, 6020
    • Novo Nordisk Investigational Site
  • Salzburg, Austria, 5020
    • Novo Nordisk Investigational Site
  • Wien, Austria, 1090
    • Novo Nordisk Investigational Site
  • Wien, Austria, 1130
    • Novo Nordisk Investigational Site
  • Wien, Austria, 1030
    • Novo Nordisk Investigational Site
  • Wien, Austria, 1170
    • Novo Nordisk Investigational Site
• Brazil
  • Porto Alegre, Brazil, 90035-170
    • Novo Nordisk Investigational Site
  • Sao Paulo, Brazil, 01221-900
    • Novo Nordisk Investigational Site
  • São Paulo, Brazil, 04022-002
    • Novo Nordisk Investigational Site
  • Parana
    • Curitiba, Parana, Brazil, 80030-110
      • Novo Nordisk Investigational Site
• Canada
  • Edmonton, Canada, T6G 2S2
    • Novo Nordisk Investigational Site
  • Montreal, Canada, H3A 1A1
    • Novo Nordisk Investigational Site
  • Quebec, Canada, G1V 4G2
    • Novo Nordisk Investigational Site
  • Toronto, Canada, M5G 1X5
    • Novo Nordisk Investigational Site
  • Toronto, Canada, M5S 1B2
    • Novo Nordisk Investigational Site
  • Vancouver, Canada, V6H 3N1
    • Novo Nordisk Investigational Site
  • Winnipeg, Canada, R3C 0N2
    • Novo Nordisk Investigational Site
  • Alberta
    • Calgary, Alberta, Canada, T2H 2G4
      • Novo Nordisk Investigational Site
  • Ontario
    • Cambridge, Ontario, Canada, N1R 7L6
      • Novo Nordisk Investigational Site
    • London, Ontario, Canada, N6A 4V2
      • Novo Nordisk Investigational Site
• Croatia
  • Zagreb, Croatia, 10 000
    • Novo Nordisk Investigational Site
• Denmark
  • Aalborg, Denmark, 9000
    • Novo Nordisk Investigational Site
  • Aarhus N, Denmark, 8200
    • Novo Nordisk Investigational Site
  • København ø, Denmark, 2100
    • Novo Nordisk Investigational Site
• Finland
  • Helsinki, Finland, 00029
    • Novo Nordisk Investigational Site
• France
  • Amiens, France
    • Novo Nordisk Investigational Site
  • Angers, France, 49000
    • Novo Nordisk Investigational Site
  • Bondy, France, 93143
    • Novo Nordisk Investigational Site
  • Lille, France, 59037
    • Novo Nordisk Investigational Site
  • MONTPELLIER cedex 5, France, 34295
    • Novo Nordisk Investigational Site
  • Marseille, France, 13009
    • Novo Nordisk Investigational Site
  • Nimes, France, 30006
    • Novo Nordisk Investigational Site
  • Strasbourg, France, 67000
    • Novo Nordisk Investigational Site
  • TOULOUSE cedex 9, France, 31059
    • Novo Nordisk Investigational Site
  • Valenciennes, France, 59322
    • Novo Nordisk Investigational Site
• Ireland
  • Dublin, Ireland, DUBLIN 7
    • Novo Nordisk Investigational Site
  • Dublin 1, Ireland
    • Novo Nordisk Investigational Site
  • Dublin 2, Ireland
    • Novo Nordisk Investigational Site
  • Dublin 8, Ireland
    • Novo Nordisk Investigational Site
• Israel
  • Petach Tikva, Israel, 49100
    • Novo Nordisk Investigational Site
• Norway
  • Bergen, Norway, 5021
    • Novo Nordisk Investigational Site
  • Trondheim, Norway, NO-7030
    • Novo Nordisk Investigational Site
  • Tønsberg, Norway, 3116
    • 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, 10-061
    • Novo Nordisk Investigational Site
  • Szczecin, Poland, 71-455
    • Novo Nordisk Investigational Site
  • Warszawa, Poland, 03-242
    • Novo Nordisk Investigational Site
  • Warszawa, Poland, 02-097
    • Novo Nordisk Investigational Site
  • Wroclaw, Poland, 50-306
    • Novo Nordisk Investigational Site
  • Zabrze, Poland, 41-800
    • Novo Nordisk Investigational Site
• Russian Federation
  • Moscow, Russian Federation, 101000
    • Novo Nordisk Investigational Site
  • Moscow, Russian Federation, 127411
    • Novo Nordisk Investigational Site
  • Novosibirsk, Russian Federation, 630047
    • Novo Nordisk Investigational Site
  • Saint-Petersburg, Russian Federation, 199034
    • Novo Nordisk Investigational Site
  • Samara, Russian Federation, 443095
    • Novo Nordisk Investigational Site
  • Tumen, Russian Federation, 625023
    • Novo Nordisk Investigational Site
• South Africa
  • Eastern Cape
    • Port Elizabeth, Eastern Cape, South Africa, 6045
      • Novo Nordisk Investigational Site
    • Port Elizabeth, Eastern Cape, South Africa, 6014
      • Novo Nordisk Investigational Site
  • Gauteng
    • Pretoria, Gauteng, South Africa, 0001
      • Novo Nordisk Investigational Site
  • KwaZulu-Natal
    • Durban, KwaZulu-Natal, South Africa, 4001
      • Novo Nordisk Investigational Site
• Spain
  • Alcoy, Spain, 03803
    • Novo Nordisk Investigational Site
  • Alicante, Spain, 03010
    • Novo Nordisk Investigational Site
  • Barcelona, Spain, 08025
    • Novo Nordisk Investigational Site
  • Madrid, Spain, 28009
    • Novo Nordisk Investigational Site
  • Santander, Spain, 39008
    • Novo Nordisk Investigational Site
  • Sevilla, Spain, 41014
    • Novo Nordisk Investigational Site
  • Valencia, Spain, 46017
    • Novo Nordisk Investigational Site
• United Kingdom
  • Belfast, United Kingdom, BT12 6BA
    • Novo Nordisk Investigational Site
  • Birmingham, United Kingdom, B9 5SS
    • Novo Nordisk Investigational Site
  • Blackburn, United Kingdom, BB2 3HH
    • Novo Nordisk Investigational Site
  • Bristol, United Kingdom, BS10 5NB
    • Novo Nordisk Investigational Site
  • Edinburgh, United Kingdom, EH16 4SA
    • Novo Nordisk Investigational Site
  • Exeter, United Kingdom, EX2 5AX
    • Novo Nordisk Investigational Site
  • Leicester, United Kingdom, LE1 5WW
    • Novo Nordisk Investigational Site
  • London, United Kingdom, W12 0NN
    • Novo Nordisk Investigational Site
  • Middlesbrough, United Kingdom, TS4 3BW
    • Novo Nordisk Investigational Site
  • Northampton, United Kingdom, NN1 5BD
    • Novo Nordisk Investigational Site
  • Norwich, United Kingdom, NR4 7UY
    • Novo Nordisk Investigational Site
  • Plymouth, United Kingdom, PL6 8BQ
    • Novo Nordisk Investigational Site
  • Southampton, United Kingdom, SO16 5YA
    • Novo Nordisk Investigational Site
  • Watford, United Kingdom, WD18 0HB
    • 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
• Planning to become pregnant and have a screening HbA1c (glycosylated haemoglobin) lesser than or equal to 9.0%, or
• Pregnant with an intrauterine singleton living foetus, 8-12 weeks pregnant when joining the trial and a HbA1c lesser than or equal to 8.0% when pregnancy is confirmed

Exclusion Criteria:

• Known or suspected hypersensitivity to the trial product(s) or related products
• Untreated hyperthyroidism or hypothyroidism
• Known or suspected abuse of alcohol or narcotics
• Cardiac problems
• Impaired kidney function
• History of severe hyperemesis gravidarum
• Treatment with in-vitro fertilisation or other medical infertility treatment
• Impaired liver function
• Uncontrolled hypertension
• Proliferative retinopathy or maculopathy requiring acute treatment
• Known to be HIV (human immunodeficiency virus) positive, Hepatitis B or Hepatitis C positive
• Any concomitant medication contraindicated in pregnancy

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Insulin detemir; Individually adjusted insulin detemir injected subcutaneously as basal insulin + individually adjusted insulin aspart injected subcutaneously as bolus insulin from randomisation (gestational week 8-12) and continued until 6 weeks after delivery. If a subject was not pregnant at randomisation, treatment was given up to a maximum of 52 weeks. For subjects who became pregnant, randomised treatment was continued until 6 weeks after delivery. Subjects who were not pregnant at 52 weeks after randomisation were withdrawn	Drug: insulin detemir; Treat-to-target, dose titration, s.c. (under the skin) injection; Drug: insulin aspart; Treat-to-target, dose titration, s.c. (under the skin) injection
Active Comparator: Neutral Protamine Hagedorn (NPH) insulin; Individually adjusted NPH insulin injected subcutaneously as basal insulin + individually adjusted insulin aspart injected subcutaneously as bolus insulin from randomisation (gestational week 8-12) and continued until 6 weeks after delivery. If a subject was not pregnant at randomisation, treatment was given up to a maximum of 52 weeks. For subjects who became pregnant, randomised treatment was continued until 6 weeks after delivery. Subjects who were not pregnant at 52 weeks after randomisation were withdrawn	Drug: insulin aspart; Treat-to-target, dose titration, s.c. (under the skin) injection; Drug: NPH insulin; Treat-to-target, dose titration, s.c. (under the skin) injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Glycosylated Haemoglobin (HbA1c) for Full Analysis Set (Pregnant Subjects) at GW 36	At gestational week (GW) 36
Glycosylated Haemoglobin (HbA1c) for Per Protocol Analysis Set (Pregnant Subjects) at GW 36	At gestational week (GW) 36

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Glycosylated Haemoglobin (HbA1c) During Pregnancy		During the pregnancy period [Visit P1 (GW 8-12), Visit P2 (GW 14), Visit P3 (GW 24), Visit P4 (GW 36), Delivery Visit (end of pregnancy)] and Follow-Up Visit ( 6 weeks after delivery)
Subjects Reaching HbA1c at or Below 6.0% Both at GW 24 and GW 36		At both Visit P3 (GW 24) and Visit P4 (GW 36)
Fasting Plasma Glucose (FPG)		During the pregnancy period [Visit P1 (GW 8-12), Visit P2 (GW 14), Visit P3 (GW 24), Visit P4 (GW 36)]
8-point Self-monitored Plasma Glucose (SMPG) Profile at GW 24	8-point SMPG was recorded 3 times prior to each visit, and the average value for each of the 8-time points was applied when presenting and analysing the SMPG data. Visit reallocation was made for the early termination visit and for the withdrawal visit.	Visit P3 (GW 24)
8-point Self Monitored Plasma Glucose (SMPG) Profile at GW 36	8-point SMPG was recorded 3 times prior to each visit, and the average value for each of the 8-time points was applied when presenting and analysing the SMPG data. Visit reallocation was made for the early termination visit and for the withdrawal visit.	Visit P4 (GW 36)
Maternal Safety - Number of Subjects With Adverse Events (AEs)	AE=any undesirable medical event occurring to a subject in a clinical trial, whether or not related to the trial product. Related AE=relationship of probable or possible. Serious adverse event (SAE) =any undesirable serious medical event as defined in protocol.	Participants were followed during the pregnancy period, an average of 9.6 months
Safety in Children - Number of Subjects (Foetuses and Newborns) With Adverse Events	AE=any undesirable medical event occurring to a subject in a clinical trial, whether or not related to the trial product. Related AE=relationship of probable or possible. SAE=any undesirable serious medical event as defined in protocol.	Foetuses/Newborns were followed during the pregnancy period, an average of 9.6 months and Follow-Up period (6 weeks after delivery)
Maternal Safety - Hypoglycaemic Episodes	All episodes include major, minor and symptoms only. Major episode : unable to self-treat. Minor: able to self-treat and plasma glucose (PG) < 3.1 mmol/L. Symptoms only: able to self-treat and no PG measurement or PG glucose ≥3.1 mmol/L. Diurnal: Episode occurring between 06.00 - 00.00, both including.	Participants were followed during the pregnancy period, an average of 9.6 months
Maternal Safety - Nocturnal Hypoglycaemic Episodes	A nocturnal episode is any episode occurring between 0.01 - 5.59, both including. It includes major, minor and symptoms only episodes. Major: unable to self-treat. Minor: able to self-treat and plasma glucose (PG) < 3.1 mmol/L. Symptoms only: able to self-treat and no PG measurement or PG glucose ≥3.1 mmol/L.	Participants were followed during the pregnancy period, an average of 9.6 months
Maternal Safety - Change in Albumin Serum Level (Biochemistry)	This is the standard safety lab parameter and is calculated as an estimate of the mean change from Visit P1 in albumin level at Follow-Up Visit (6 weeks after delivery).	Visit P1 (GW 8-12), Follow-Up (FU) Visit (6 weeks after delivery)
Maternal Safety - Change in Alanine Aminotransferase Serum Level (Biochemistry)	This is the standard safety lab parameter and is calculated as an estimate of the mean change from Visit P1 in alanine aminotransferase level at Follow-Up Visit (6 weeks after delivery).	Visit P1 (GW 8-12), Follow-Up (FU) Visit (6 weeks after delivery)
Maternal Safety - Change in Alkaline Phosphatase Serum Level (Biochemistry)	This is the standard safety lab parameter and is calculated as an estimate of the mean change from Visit P1 in alkaline phosphatase level at Follow-Up Visit (6 weeks after delivery).	Visit P1 (GW 8-12), Follow-Up (FU) Visit (6 weeks after delivery)
Maternal Safety - Change in Creatinine Serum Level (Biochemistry)	This is the standard safety lab parameter and is calculated as an estimate of the mean change from Visit P1 in creatinine serum level at Follow-Up Visit (6 weeks after delivery).	Visit P1 (GW 8-12), Follow-Up (FU) Visit (6 weeks after delivery)
Maternal Safety - Change in Lactate Dehydrogenase Serum Level (Biochemistry)	This is the standard safety lab parameter and is calculated as an estimate of the mean change from Visit P1 in lactate dehydrogenase serum level at Follow-Up Visit (6 weeks after delivery).	Visit P1 (GW 8-12), Follow-Up (FU) Visit (6 weeks after delivery)
Maternal Safety - Change in Potassium Serum Level (Biochemistry)	This is the standard safety lab parameter and is calculated as an estimate of the mean change from Visit P1 in potassium serum level at Follow-Up Visit (6 weeks after delivery).	Visit P1 (GW 8-12), Follow-Up (FU) Visit (6 weeks after delivery)
Maternal Safety - Change in Sodium Serum Level (Biochemistry)	This is the standard safety lab parameter and is calculated as an estimate of the mean change from Visit P1 in sodium serum level at Follow-Up Visit (6 weeks after delivery).	Visit P1 (GW 8-12), Follow-Up (FU) Visit (6 weeks after delivery)
Maternal Safety - Change in Total Protein Serum Level (Biochemistry)	This is the standard safety lab parameter and is calculated as an estimate of the mean change from Visit P1 in total protein serum level at Follow-Up Visit (6 weeks after delivery).	Visit P1 (GW 8-12), Follow-Up (FU) Visit (6 weeks after delivery)
Maternal Safety - Change in Haemoglobin Level (Haematology)	This is the standard safety lab parameter and is calculated as an estimate of the mean change from Visit P1 in haemoglobin level at Follow-Up Visit (6 weeks after delivery).	Visit P1 (GW 8-12), Follow-Up (FU) Visit (6 weeks after delivery)
Maternal Safety - Change in Leukocytes Level (Haematology)	This is the standard safety lab parameter and is calculated as an estimate of the mean change from Visit P1 in leukocytes level at Follow-Up Visit (6 weeks after delivery).	Visit P1 (GW 8-12), Follow-Up (FU) Visit (6 weeks after delivery)
Maternal Safety - Change in Thrombocytes Level (Haematology)	This is the standard safety lab parameter and is calculated as an estimate of the mean change from Visit P1 in thrombocytes level at Follow-Up Visit (6 weeks after delivery).	Visit P1 (GW 8-12), Follow-Up (FU) Visit (6 weeks after delivery)
Maternal Safety - Change in Urine Albumin Level (Urinalysis)	This is the standard safety lab parameter and calculated as an estimate of the mean change from Visit P1 in urine albumin level at Follow-Up Visit (6 weeks after delivery).	Visit P1 (GW 8-12), Follow-Up (FU) Visit (6 weeks after delivery)
Maternal Safety - Change in Albumin/Creatinine Ratio (Urinalysis)	This is the standard safety lab parameter and calculated as an estimate of the mean change from Visit P1 in albumin/creatinine ratio at Follow-Up Visit (6 weeks after delivery).	Visit P1 (GW 8-12), Follow-Up (FU) Visit (6 weeks after delivery)
Maternal Safety - Change in Urine N (Creatinine) (Urinalysis)	This is the standard safety lab parameter and calculated as an estimate of the mean change from Visit P1 in Urine-N (creatinine) level at Follow-Up Visit (6 weeks after delivery).	Visit P1 (GW 8-12), Follow-Up (FU) Visit (6 weeks after delivery)
Maternal Safety - Change in Insulin Detemir Specific Antibodies	Change in concentrations of values for insulin detemir specific antibodies from baseline to Visit P4 was calculated. The unit for measuring antibody levels is amount of tracer bound to the antibodies in the precipitate (B) expressed in percentage of the total amount of tracer (T) added to the mixture (%B/T). Samples were taken before 1st dosing.	Baseline, Visit P4 (GW 36). Baseline is Visit 2 (randomisation visit, within 3 weeks of screening) for subjects not pregnant at randomisation and Visit P1 (GW 8-12) for pregnant subjects at randomisation.
Maternal Safety - Change in Insulin Aspart Specific Antibodies	Change in concentrations values for insulin aspart specific antibodies from baseline to Visit P4 was calculated. The unit for measuring antibody levels is amount of tracer bound to the antibodies in the precipitate (B) expressed in percentage of the total amount of tracer (T) added to the mixture (%B/T). Samples were taken before 1st dosing.	Baseline, Visit P4 (GW 36). Baseline is Visit 2 (randomisation visit, within 3 weeks of screening) for subjects not pregnant at randomisation and Visit P1 (GW 8-12) for pregnant subjects at randomisation.
Maternal Safety - Change in Insulin Detemir/Insulin Aspart Cross Reacting Antibodies	Change in concentrations values for insulin detemir/aspart cross-reacting antibodies from baseline to Visit P4 was calculated. The unit for measuring antibody levels is amount of tracer bound to the antibodies in the precipitate (B) expressed in percentage of the total amount of tracer (T) added to the mixture (%B/T). Samples were taken before 1st dosing	Baseline, Visit P4 (GW 36). Baseline is Visit 2 (randomisation visit, within 3 weeks of screening) for subjects not pregnant at randomisation and Visit P1 (GW 8-12) for pregnant subjects at randomisation.
Pregnancy Outcome Safety - Level of Detemir Specific Antibodies (AB) in Umbilical Cord Blood	Antibodies were measured in a subtraction radioimmunoassay and expressed as antibody bound tracer relative to the total amount of tracer (%B/T).	At Delivery (End of Pregnancy)
Pregnancy Outcome Safety - Level of Aspart Specific Antibodies (AB) in Umbilical Cord Blood	Antibodies were measured in a subtraction radioimmunoassay and expressed as antibody bound tracer relative to the total amount of tracer (%B/T)	At Delivery (End of Pregnancy)
Pregnancy Outcome Safety - Level of Cross-Reacting Antibodies (AB) in Umbilical Cord Blood	Antibodies were measured in a subtraction radioimmunoassay and expressed as antibody bound tracer relative to the total amount of tracer (%B/T).	At Delivery (End of Pregnancy)
Ratio Between Detemir Specific Antibodies in Cord Blood and Maternal Antibodies	Cord blood (at delivery) vs. Maternal Blood at Visit P4 (GW 36)	At Delivery (End of Pregnancy) and at Visit P4 (GW 36)
Pregnancy Outcome Safety - Level of Insulin Detemir in Umbilical Cord Blood		At Delivery
Maternal Safety - Change From Visit P1 in Body Weight During Pregnancy by Visit	Change in the body weight was summarised by treatment.	Visit P1 (GW (8-12), Visit P2 (GW 14), Visit P3 (GW 24), Visit P4 (GW 36)
Maternal Safety - Change From Visit P1 in Systolic Blood Pressure During Pregnancy and at Follow-Up by Visit	Change in the systolic blood pressure was summarised by treatment.	Visit P1 (GW (8-12)), Visit P2 (GW 14), Visit P3 (GW 24), Visit P4 (GW 36), Follow-Up (FU) Visit (6 weeks after delivery)
Maternal Safety - Change From Visit P1 in Diastolic Blood Pressure During Pregnancy and at Follow-Up by Visit	Change in the diastolic blood pressure was summarised by treatment.	Visit P1 (GW (8-12)), Visit P2 (GW 14), Visit P3 (GW 24), Visit P4 (GW 36), Follow-Up (FU) Visit (6 weeks after delivery)
Maternal Safety - Change From Visit P1 in Pulse During Pregnancy and at Follow-Up	Change in the pulse was summarised by treatment.	Visit P1 (GW (8-12), Visit P2 (GW 14), Visit P3 (GW 24), Visit P4 (GW 36), Follow-Up Visit (6 weeks after delivery)
Maternal Safety - Electrocardiogram (ECG)	The number of subjects having a electrocardiogram (ECG) that changed from 'Normal' or 'Abnormal, not clinically significant' (at Visit 1, 3 weeks before randomisation) to 'Abnormal, clinically significant' (at Follow-Up). 'Abnormal, Clinically significant' is an abnormality that suggests a disease and/or organ toxicity and is of a severity, which requires active management.	Follow-Up (6 weeks after delivery)
Maternal Safety - Acceleration of Retinopathy in Any Eye	Acceleration of Retinopathy is defined as worsening of fundoscopy/fundusphotography findings from GW 8-12 (Visit P1) to follow-up on one or both eyes.	From GW 8-12 (Visit P1) to Follow-Up (6 weeks after delivery)
Maternal Safety - Acceleration of Nephropathy	Acceleration of nephropathy was defined as a change from a low U-albumin:U-creatinine ratio ≤33.93 mg/mmol to a high U-albumin:U-creatinine ratio > 33.93 mg/mmol from GW 8-12 (Visit P1) to the follow-up visit.	From GW 8-12 (Visit P1) to Follow-Up (6 weeks after delivery)
Maternal Safety - Mode of Delivery	Non-Planned Caesarean Section is a procedure which takes place ≤8h prior to delivery. Planned Caesarean Section takes place >8h prior to delivery.	At Delivery Visit
Pregnancy Outcome at Delivery	Induced abortion means interruption of a living pregnancy < 22 completed weeks. Early foetal death means death before 22 completed GWs. Stillbirth indicates death between at or after 22 GW and at or before delivery.	Delivery Visit
Pregnancy Outcome at Follow-Up	Induced abortion means interruption of a living pregnancy < 22 completed weeks. Early foetal death means death before 22 completed GWs. Perinatal Death means death of a foetus/infant between ≥ 22 completed GWs and < 1 completed week after delivery. Neonatal Death means death between at or after 7 completed days and before 28 completed days after delivery. Death During Follow-Up means death between at or after 28 days after delivery and at or before Follow-Up.	Follow-Up (6 weeks after delivery)
Safety - Total Daily Insulin Dose During Pregnancy		Visit P2 (GW 14), Visit P3 (GW 24), Visit P4 (GW 36), Follow-Up (6 weeks after delivery)
Safety - Composite Pregnancy Outcome	Wt. corresponds to weight of live-born infants. Pre-term delivery: delivery before 37 completed GWs including abortions. Early foetal death: death before 22 completed GWs. Perinatal mortality: death of a foetus/infant between ≥ 22 completed GWs and < 1 completed week after delivery. Neonatal mortality: post-partum after 7 completed days and before 28 completed days after delivery. Major-malformation: a life threatening structural anomaly or one likely to cause significant impairment of health or functional capacity and needs medical or surgical treatment.	End of Pregnancy
Ratio Between Aspart Specific Antibodies in Cord Blood and Maternal Antibodies	Cord blood (at delivery) vs. Maternal Blood at Visit P4 (GW 36)	At Delivery (End of Pregnancy) and at Visit P4 (GW 36)
Ratio Between Cross-reacting Antibodies in Cord Blood and Maternal Antibodies	Cord blood (at delivery) vs. Maternal Blood at Visit P4 (GW 36)	At Delivery (End of Pregnancy) and at Visit P4 (GW 36)

Collaborators and Investigators

• Sponsor: Novo Nordisk A/S

Publications and helpful links

General Publications

• Mathiesen ER, Damm P, Jovanovic L, McCance DR, Thyregod C, Jensen AB, Hod M. Basal insulin analogues in diabetic pregnancy: a literature review and baseline results of a randomised, controlled trial in type 1 diabetes. Diabetes Metab Res Rev. 2011 Sep;27(6):543-51. doi: 10.1002/dmrr.1213.
• Mathiesen ER, Hod M, Ivanisevic M, Duran Garcia S, Brondsted L, Jovanovic L, Damm P, McCance DR; Detemir in Pregnancy Study Group. Maternal efficacy and safety outcomes in a randomized, controlled trial comparing insulin detemir with NPH insulin in 310 pregnant women with type 1 diabetes. Diabetes Care. 2012 Oct;35(10):2012-7. doi: 10.2337/dc11-2264. Epub 2012 Jul 30.
• Hod M, Mathiesen ER, Jovanovic L, McCance DR, Ivanisevic M, Duran-Garcia S, Brondsted L, Nazeri A, Damm P. A randomized trial comparing perinatal outcomes using insulin detemir or neutral protamine Hagedorn in type 1 diabetes. J Matern Fetal Neonatal Med. 2014 Jan;27(1):7-13. doi: 10.3109/14767058.2013.799650. Epub 2013 Jun 5.

Helpful Links

• Clinical Trials at Novo Nordisk

Study record dates

Study Major Dates

• Study Start: May 1, 2007
• Primary Completion (Actual): August 1, 2010
• Study Completion (Actual): August 1, 2010

Study Registration Dates

• First Submitted: May 15, 2007
• First Submitted That Met QC Criteria: May 15, 2007
• First Posted (Estimate): May 16, 2007

Study Record Updates

• Last Update Posted (Actual): March 10, 2017
• Last Update Submitted That Met QC Criteria: January 30, 2017
• Last Verified: January 1, 2017

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; Insulin Detemir; Insulin, Isophane; Isophane Insulin, Human; Isophane insulin, beef
• Other Study ID Numbers: NN304-1687; 2006-004861-33 (EudraCT Number)