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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT00474045




Registration number
NCT00474045
Ethics application status
Date submitted
15/05/2007
Date registered
16/05/2007
Date last updated
10/03/2017

Titles & IDs
Public title
Efficacy and Safety of Insulin Detemir Versus Neutral Protamine Hagedorn (NPH) Insulin in Pregnant Women With Type 1 Diabetes
Scientific title
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
Secondary ID [1] 0 0
2006-004861-33
Secondary ID [2] 0 0
NN304-1687
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Diabetes 0 0
Diabetes Mellitus, Type 1 0 0
Condition category
Condition code
Metabolic and Endocrine 0 0 0 0
Diabetes

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - insulin detemir
Treatment: Drugs - NPH insulin
Treatment: Drugs - insulin aspart

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 Subjects who were not pregnant at 52 weeks after randomisation were withdrawn

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 Subjects who were not pregnant at 52 weeks after randomisation were withdrawn


Treatment: Drugs: insulin detemir
Treat-to-target, dose titration, s.c. (under the skin) injection

Treatment: Drugs: NPH insulin
Treat-to-target, dose titration, s.c. (under the skin) injection

Treatment: Drugs: insulin aspart
Treat-to-target, dose titration, s.c. (under the skin) injection
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Glycosylated Haemoglobin (HbA1c) for Full Analysis Set (Pregnant Subjects) at GW 36
Timepoint [1] 0 0
At gestational week (GW) 36
Primary outcome [2] 0 0
Glycosylated Haemoglobin (HbA1c) for Per Protocol Analysis Set (Pregnant Subjects) at GW 36
Timepoint [2] 0 0
At gestational week (GW) 36
Secondary outcome [1] 0 0
Glycosylated Haemoglobin (HbA1c) During Pregnancy
Timepoint [1] 0 0
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)
Secondary outcome [2] 0 0
Subjects Reaching HbA1c at or Below 6.0% Both at GW 24 and GW 36
Timepoint [2] 0 0
At both Visit P3 (GW 24) and Visit P4 (GW 36)
Secondary outcome [3] 0 0
Fasting Plasma Glucose (FPG)
Timepoint [3] 0 0
During the pregnancy period [Visit P1 (GW 8-12), Visit P2 (GW 14), Visit P3 (GW 24), Visit P4 (GW 36)]
Secondary outcome [4] 0 0
8-point Self-monitored Plasma Glucose (SMPG) Profile at GW 24
Timepoint [4] 0 0
Visit P3 (GW 24)
Secondary outcome [5] 0 0
8-point Self Monitored Plasma Glucose (SMPG) Profile at GW 36
Timepoint [5] 0 0
Visit P4 (GW 36)
Secondary outcome [6] 0 0
Maternal Safety - Number of Subjects With Adverse Events (AEs)
Timepoint [6] 0 0
Participants were followed during the pregnancy period, an average of 9.6 months
Secondary outcome [7] 0 0
Safety in Children - Number of Subjects (Foetuses and Newborns) With Adverse Events
Timepoint [7] 0 0
Foetuses/Newborns were followed during the pregnancy period, an average of 9.6 months and Follow-Up period (6 weeks after delivery)
Secondary outcome [8] 0 0
Maternal Safety - Hypoglycaemic Episodes
Timepoint [8] 0 0
Participants were followed during the pregnancy period, an average of 9.6 months
Secondary outcome [9] 0 0
Maternal Safety - Nocturnal Hypoglycaemic Episodes
Timepoint [9] 0 0
Participants were followed during the pregnancy period, an average of 9.6 months
Secondary outcome [10] 0 0
Maternal Safety - Change in Albumin Serum Level (Biochemistry)
Timepoint [10] 0 0
Visit P1 (GW 8-12), Follow-Up (FU) Visit (6 weeks after delivery)
Secondary outcome [11] 0 0
Maternal Safety - Change in Alanine Aminotransferase Serum Level (Biochemistry)
Timepoint [11] 0 0
Visit P1 (GW 8-12), Follow-Up (FU) Visit (6 weeks after delivery)
Secondary outcome [12] 0 0
Maternal Safety - Change in Alkaline Phosphatase Serum Level (Biochemistry)
Timepoint [12] 0 0
Visit P1 (GW 8-12), Follow-Up (FU) Visit (6 weeks after delivery)
Secondary outcome [13] 0 0
Maternal Safety - Change in Creatinine Serum Level (Biochemistry)
Timepoint [13] 0 0
Visit P1 (GW 8-12), Follow-Up (FU) Visit (6 weeks after delivery)
Secondary outcome [14] 0 0
Maternal Safety - Change in Lactate Dehydrogenase Serum Level (Biochemistry)
Timepoint [14] 0 0
Visit P1 (GW 8-12), Follow-Up (FU) Visit (6 weeks after delivery)
Secondary outcome [15] 0 0
Maternal Safety - Change in Potassium Serum Level (Biochemistry)
Timepoint [15] 0 0
Visit P1 (GW 8-12), Follow-Up (FU) Visit (6 weeks after delivery)
Secondary outcome [16] 0 0
Maternal Safety - Change in Sodium Serum Level (Biochemistry)
Timepoint [16] 0 0
Visit P1 (GW 8-12), Follow-Up (FU) Visit (6 weeks after delivery)
Secondary outcome [17] 0 0
Maternal Safety - Change in Total Protein Serum Level (Biochemistry)
Timepoint [17] 0 0
Visit P1 (GW 8-12), Follow-Up (FU) Visit (6 weeks after delivery)
Secondary outcome [18] 0 0
Maternal Safety - Change in Haemoglobin Level (Haematology)
Timepoint [18] 0 0
Visit P1 (GW 8-12), Follow-Up (FU) Visit (6 weeks after delivery)
Secondary outcome [19] 0 0
Maternal Safety - Change in Leukocytes Level (Haematology)
Timepoint [19] 0 0
Visit P1 (GW 8-12), Follow-Up (FU) Visit (6 weeks after delivery)
Secondary outcome [20] 0 0
Maternal Safety - Change in Thrombocytes Level (Haematology)
Timepoint [20] 0 0
Visit P1 (GW 8-12), Follow-Up (FU) Visit (6 weeks after delivery)
Secondary outcome [21] 0 0
Maternal Safety - Change in Urine Albumin Level (Urinalysis)
Timepoint [21] 0 0
Visit P1 (GW 8-12), Follow-Up (FU) Visit (6 weeks after delivery)
Secondary outcome [22] 0 0
Maternal Safety - Change in Albumin/Creatinine Ratio (Urinalysis)
Timepoint [22] 0 0
Visit P1 (GW 8-12), Follow-Up (FU) Visit (6 weeks after delivery)
Secondary outcome [23] 0 0
Maternal Safety - Change in Urine N (Creatinine) (Urinalysis)
Timepoint [23] 0 0
Visit P1 (GW 8-12), Follow-Up (FU) Visit (6 weeks after delivery)
Secondary outcome [24] 0 0
Maternal Safety - Change in Insulin Detemir Specific Antibodies
Timepoint [24] 0 0
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.
Secondary outcome [25] 0 0
Maternal Safety - Change in Insulin Aspart Specific Antibodies
Timepoint [25] 0 0
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.
Secondary outcome [26] 0 0
Maternal Safety - Change in Insulin Detemir/Insulin Aspart Cross Reacting Antibodies
Timepoint [26] 0 0
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.
Secondary outcome [27] 0 0
Pregnancy Outcome Safety - Level of Detemir Specific Antibodies (AB) in Umbilical Cord Blood
Timepoint [27] 0 0
At Delivery (End of Pregnancy)
Secondary outcome [28] 0 0
Pregnancy Outcome Safety - Level of Aspart Specific Antibodies (AB) in Umbilical Cord Blood
Timepoint [28] 0 0
At Delivery (End of Pregnancy)
Secondary outcome [29] 0 0
Pregnancy Outcome Safety - Level of Cross-Reacting Antibodies (AB) in Umbilical Cord Blood
Timepoint [29] 0 0
At Delivery (End of Pregnancy)
Secondary outcome [30] 0 0
Ratio Between Detemir Specific Antibodies in Cord Blood and Maternal Antibodies
Timepoint [30] 0 0
At Delivery (End of Pregnancy) and at Visit P4 (GW 36)
Secondary outcome [31] 0 0
Pregnancy Outcome Safety - Level of Insulin Detemir in Umbilical Cord Blood
Timepoint [31] 0 0
At Delivery
Secondary outcome [32] 0 0
Maternal Safety - Change From Visit P1 in Body Weight During Pregnancy by Visit
Timepoint [32] 0 0
Visit P1 (GW (8-12), Visit P2 (GW 14), Visit P3 (GW 24), Visit P4 (GW 36)
Secondary outcome [33] 0 0
Maternal Safety - Change From Visit P1 in Systolic Blood Pressure During Pregnancy and at Follow-Up by Visit
Timepoint [33] 0 0
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)
Secondary outcome [34] 0 0
Maternal Safety - Change From Visit P1 in Diastolic Blood Pressure During Pregnancy and at Follow-Up by Visit
Timepoint [34] 0 0
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)
Secondary outcome [35] 0 0
Maternal Safety - Change From Visit P1 in Pulse During Pregnancy and at Follow-Up
Timepoint [35] 0 0
Visit P1 (GW (8-12), Visit P2 (GW 14), Visit P3 (GW 24), Visit P4 (GW 36), Follow-Up Visit (6 weeks after delivery)
Secondary outcome [36] 0 0
Maternal Safety - Electrocardiogram (ECG)
Timepoint [36] 0 0
Follow-Up (6 weeks after delivery)
Secondary outcome [37] 0 0
Maternal Safety - Acceleration of Retinopathy in Any Eye
Timepoint [37] 0 0
From GW 8-12 (Visit P1) to Follow-Up (6 weeks after delivery)
Secondary outcome [38] 0 0
Maternal Safety - Acceleration of Nephropathy
Timepoint [38] 0 0
From GW 8-12 (Visit P1) to Follow-Up (6 weeks after delivery)
Secondary outcome [39] 0 0
Maternal Safety - Mode of Delivery
Timepoint [39] 0 0
At Delivery Visit
Secondary outcome [40] 0 0
Pregnancy Outcome at Delivery
Timepoint [40] 0 0
Delivery Visit
Secondary outcome [41] 0 0
Pregnancy Outcome at Follow-Up
Timepoint [41] 0 0
Follow-Up (6 weeks after delivery)
Secondary outcome [42] 0 0
Safety - Total Daily Insulin Dose During Pregnancy
Timepoint [42] 0 0
Visit P2 (GW 14), Visit P3 (GW 24), Visit P4 (GW 36), Follow-Up (6 weeks after delivery)
Secondary outcome [43] 0 0
Safety - Composite Pregnancy Outcome
Timepoint [43] 0 0
End of Pregnancy
Secondary outcome [44] 0 0
Ratio Between Aspart Specific Antibodies in Cord Blood and Maternal Antibodies
Timepoint [44] 0 0
At Delivery (End of Pregnancy) and at Visit P4 (GW 36)
Secondary outcome [45] 0 0
Ratio Between Cross-reacting Antibodies in Cord Blood and Maternal Antibodies
Timepoint [45] 0 0
At Delivery (End of Pregnancy) and at Visit P4 (GW 36)

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Sex
Females
Can healthy volunteers participate?
No
Key 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 design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/05/2007
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/08/2010
Sample size
Target
Accrual to date
Final
470
Recruitment in Australia
Recruitment state(s)
NSW,SA
Recruitment hospital [1] 0 0
Novo Nordisk Investigational Site - Broadmeadow
Recruitment hospital [2] 0 0
Novo Nordisk Investigational Site - Camperdown
Recruitment hospital [3] 0 0
Novo Nordisk Investigational Site - St Leonards
Recruitment hospital [4] 0 0
Novo Nordisk Investigational Site - Elizabeth Vale
Recruitment hospital [5] 0 0
Novo Nordisk Investigational Site - Clayton
Recruitment hospital [6] 0 0
Novo Nordisk Investigational Site - Garran
Recruitment hospital [7] 0 0
Novo Nordisk Investigational Site - South Brisbane
Recruitment hospital [8] 0 0
Novo Nordisk Investigational Site - Subiaco
Recruitment hospital [9] 0 0
Novo Nordisk Investigational Site - Wollongong
Recruitment postcode(s) [1] 0 0
2292 - Broadmeadow
Recruitment postcode(s) [2] 0 0
2050 - Camperdown
Recruitment postcode(s) [3] 0 0
2065 - St Leonards
Recruitment postcode(s) [4] 0 0
5112 - Elizabeth Vale
Recruitment postcode(s) [5] 0 0
3168 - Clayton
Recruitment postcode(s) [6] 0 0
2605 - Garran
Recruitment postcode(s) [7] 0 0
4101 - South Brisbane
Recruitment postcode(s) [8] 0 0
6008 - Subiaco
Recruitment postcode(s) [9] 0 0
2500 - Wollongong
Recruitment outside Australia
Country [1] 0 0
Argentina
State/province [1] 0 0
Buenos Aires
Country [2] 0 0
Argentina
State/province [2] 0 0
Mar del Plata
Country [3] 0 0
Argentina
State/province [3] 0 0
Pcia de Cordoba
Country [4] 0 0
Argentina
State/province [4] 0 0
Salta
Country [5] 0 0
Austria
State/province [5] 0 0
Feldkirch
Country [6] 0 0
Austria
State/province [6] 0 0
Innsbruck
Country [7] 0 0
Austria
State/province [7] 0 0
Salzburg
Country [8] 0 0
Austria
State/province [8] 0 0
Wien
Country [9] 0 0
Brazil
State/province [9] 0 0
Parana
Country [10] 0 0
Brazil
State/province [10] 0 0
Porto Alegre
Country [11] 0 0
Brazil
State/province [11] 0 0
Sao Paulo
Country [12] 0 0
Brazil
State/province [12] 0 0
São Paulo
Country [13] 0 0
Canada
State/province [13] 0 0
Alberta
Country [14] 0 0
Canada
State/province [14] 0 0
Ontario
Country [15] 0 0
Canada
State/province [15] 0 0
Edmonton
Country [16] 0 0
Canada
State/province [16] 0 0
Montreal
Country [17] 0 0
Canada
State/province [17] 0 0
Quebec
Country [18] 0 0
Canada
State/province [18] 0 0
Toronto
Country [19] 0 0
Canada
State/province [19] 0 0
Vancouver
Country [20] 0 0
Canada
State/province [20] 0 0
Winnipeg
Country [21] 0 0
Croatia
State/province [21] 0 0
Zagreb
Country [22] 0 0
Denmark
State/province [22] 0 0
Aalborg
Country [23] 0 0
Denmark
State/province [23] 0 0
Aarhus N
Country [24] 0 0
Denmark
State/province [24] 0 0
København ø
Country [25] 0 0
Finland
State/province [25] 0 0
Helsinki
Country [26] 0 0
France
State/province [26] 0 0
Amiens
Country [27] 0 0
France
State/province [27] 0 0
Angers
Country [28] 0 0
France
State/province [28] 0 0
Bondy
Country [29] 0 0
France
State/province [29] 0 0
Lille
Country [30] 0 0
France
State/province [30] 0 0
Marseille
Country [31] 0 0
France
State/province [31] 0 0
MONTPELLIER cedex 5
Country [32] 0 0
France
State/province [32] 0 0
Nimes
Country [33] 0 0
France
State/province [33] 0 0
Strasbourg
Country [34] 0 0
France
State/province [34] 0 0
TOULOUSE cedex 9
Country [35] 0 0
France
State/province [35] 0 0
Valenciennes
Country [36] 0 0
Ireland
State/province [36] 0 0
Dublin 1
Country [37] 0 0
Ireland
State/province [37] 0 0
Dublin 2
Country [38] 0 0
Ireland
State/province [38] 0 0
Dublin 8
Country [39] 0 0
Ireland
State/province [39] 0 0
Dublin
Country [40] 0 0
Israel
State/province [40] 0 0
Petach Tikva
Country [41] 0 0
Norway
State/province [41] 0 0
Bergen
Country [42] 0 0
Norway
State/province [42] 0 0
Trondheim
Country [43] 0 0
Norway
State/province [43] 0 0
Tønsberg
Country [44] 0 0
Poland
State/province [44] 0 0
Krakow
Country [45] 0 0
Poland
State/province [45] 0 0
Lodz
Country [46] 0 0
Poland
State/province [46] 0 0
Lublin
Country [47] 0 0
Poland
State/province [47] 0 0
Olsztyn
Country [48] 0 0
Poland
State/province [48] 0 0
Szczecin
Country [49] 0 0
Poland
State/province [49] 0 0
Warszawa
Country [50] 0 0
Poland
State/province [50] 0 0
Wroclaw
Country [51] 0 0
Poland
State/province [51] 0 0
Zabrze
Country [52] 0 0
Russian Federation
State/province [52] 0 0
Moscow
Country [53] 0 0
Russian Federation
State/province [53] 0 0
Novosibirsk
Country [54] 0 0
Russian Federation
State/province [54] 0 0
Saint-Petersburg
Country [55] 0 0
Russian Federation
State/province [55] 0 0
Samara
Country [56] 0 0
Russian Federation
State/province [56] 0 0
Tumen
Country [57] 0 0
South Africa
State/province [57] 0 0
Eastern Cape
Country [58] 0 0
South Africa
State/province [58] 0 0
Gauteng
Country [59] 0 0
South Africa
State/province [59] 0 0
KwaZulu-Natal
Country [60] 0 0
Spain
State/province [60] 0 0
Alcoy
Country [61] 0 0
Spain
State/province [61] 0 0
Alicante
Country [62] 0 0
Spain
State/province [62] 0 0
Barcelona
Country [63] 0 0
Spain
State/province [63] 0 0
Madrid
Country [64] 0 0
Spain
State/province [64] 0 0
Santander
Country [65] 0 0
Spain
State/province [65] 0 0
Sevilla
Country [66] 0 0
Spain
State/province [66] 0 0
Valencia
Country [67] 0 0
United Kingdom
State/province [67] 0 0
Belfast
Country [68] 0 0
United Kingdom
State/province [68] 0 0
Birmingham
Country [69] 0 0
United Kingdom
State/province [69] 0 0
Blackburn
Country [70] 0 0
United Kingdom
State/province [70] 0 0
Bristol
Country [71] 0 0
United Kingdom
State/province [71] 0 0
Edinburgh
Country [72] 0 0
United Kingdom
State/province [72] 0 0
Exeter
Country [73] 0 0
United Kingdom
State/province [73] 0 0
Leicester
Country [74] 0 0
United Kingdom
State/province [74] 0 0
London
Country [75] 0 0
United Kingdom
State/province [75] 0 0
Middlesbrough
Country [76] 0 0
United Kingdom
State/province [76] 0 0
Northampton
Country [77] 0 0
United Kingdom
State/province [77] 0 0
Norwich
Country [78] 0 0
United Kingdom
State/province [78] 0 0
Plymouth
Country [79] 0 0
United Kingdom
State/province [79] 0 0
Southampton
Country [80] 0 0
United Kingdom
State/province [80] 0 0
Watford

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Novo Nordisk A/S
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
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).
Trial website
https://clinicaltrials.gov/ct2/show/NCT00474045
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Global Clinical Registry (GCR, 1452)
Address 0 0
Novo Nordisk A/S
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT00474045