Trial Review

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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/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 Subjects who were not pregnant at 52 weeks after randomisation were withdrawn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 Subjects who were not pregnant at 52 weeks after randomisation were withdrawn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
Trial website
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

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents


Results are available at https://clinicaltrials.gov/study/NCT00474045