DiabetesPhase 3NCT00474045
Efficacy and Safety of Insulin Detemir Versus Neutral Protamine Hagedorn (NPH) Insulin in Pregnant Women With Type 1 Diabetes
A Phase 3 study testing insulin detemir, NPH insulin and insulin aspart in people with Diabetes and Diabetes Mellitus, Type 1, run by Novo Nordisk A/S at 98 sites in 17 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Diabetes, Diabetes Mellitus, Type 1
- What is being tested?
- insulin detemir, NPH insulin and insulin aspart
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 470 participants
- Where
- 98 sitesin 17 countries
- Study dates
- May 2007to Aug 2010
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 12Show fewer
- 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
Trial locations and contacts
98 sites in 17 countries.
98 sites in 17 countries
United Kingdom14 sites
Novo Nordisk Investigational Site
Belfast, BT12 6BA
Novo Nordisk Investigational Site
Birmingham, B9 5SS
Novo Nordisk Investigational Site
Blackburn, BB2 3HH
Novo Nordisk Investigational Site
Bristol, BS10 5NB
Novo Nordisk Investigational Site
Edinburgh, EH16 4SA
Novo Nordisk Investigational Site
Exeter, EX2 5AX
Novo Nordisk Investigational Site
Leicester, LE1 5WW
Novo Nordisk Investigational Site
London, W12 0NN
Novo Nordisk Investigational Site
Middlesbrough, TS4 3BW
Novo Nordisk Investigational Site
Northampton, NN1 5BD
Novo Nordisk Investigational Site
Norwich, NR4 7UY
Novo Nordisk Investigational Site
Plymouth, PL6 8BQ
Novo Nordisk Investigational Site
Southampton, SO16 5YA
Novo Nordisk Investigational Site
Watford, WD18 0HB
Canada10 sites
Novo Nordisk Investigational Site
Calgary, Alberta, T2H 2G4
Novo Nordisk Investigational Site
Cambridge, Ontario, N1R 7L6
Novo Nordisk Investigational Site
Edmonton, T6G 2S2
Novo Nordisk Investigational Site
London, Ontario, N6A 4V2
Novo Nordisk Investigational Site
Montreal, H3A 1A1
Novo Nordisk Investigational Site
Québec, G1V 4G2
Novo Nordisk Investigational Site
Toronto, M5G 1X5
Novo Nordisk Investigational Site
Toronto, M5S 1B2
Novo Nordisk Investigational Site
Vancouver, V6H 3N1
Novo Nordisk Investigational Site
Winnipeg, R3C 0N2
France10 sites
Novo Nordisk Investigational Site
Amiens
Novo Nordisk Investigational Site
Angers, 49000
Novo Nordisk Investigational Site
Bondy, 93143
Novo Nordisk Investigational Site
Lille, 59037
Novo Nordisk Investigational Site
Marseille, 13009
Novo Nordisk Investigational Site
Montpellier, 34295
Novo Nordisk Investigational Site
Nîmes, 30006
Novo Nordisk Investigational Site
Strasbourg, 67000
Novo Nordisk Investigational Site
Toulouse, 31059
Novo Nordisk Investigational Site
Valenciennes, 59322
Australia9 sites
Novo Nordisk Investigational Site
Broadmeadow, New South Wales, 2292
Novo Nordisk Investigational Site
Camperdown, New South Wales, 2050
Novo Nordisk Investigational Site
Clayton, 3168
Novo Nordisk Investigational Site
Elizabeth Vale, South Australia, 5112
Novo Nordisk Investigational Site
Garran, 2605
Novo Nordisk Investigational Site
South Brisbane, 4101
Novo Nordisk Investigational Site
St Leonards, New South Wales, 2065
Novo Nordisk Investigational Site
Subiaco, 6008
Novo Nordisk Investigational Site
Wollongong, 2500
Poland9 sites
Novo Nordisk Investigational Site
Krakow, 31-501
Novo Nordisk Investigational Site
Lodz, 93-338
Novo Nordisk Investigational Site
Lublin, 20-081
Novo Nordisk Investigational Site
Olsztyn, 10-061
Novo Nordisk Investigational Site
Szczecin, 71-455
Novo Nordisk Investigational Site
Warsaw, 02-097
Novo Nordisk Investigational Site
Warsaw, 03-242
Novo Nordisk Investigational Site
Wroclaw, 50-306
Novo Nordisk Investigational Site
Zabrze, 41-800
Argentina7 sites
Novo Nordisk Investigational Site
Buenos Aires, B1704ETD
Novo Nordisk Investigational Site
Buenos Aires, C1155ADP
Novo Nordisk Investigational Site
Buenos Aires, C1181ACH
Novo Nordisk Investigational Site
Buenos Aires, C1246ABQ
Novo Nordisk Investigational Site
Mar del Plata, B7602CBM
Novo Nordisk Investigational Site
Pcia de Cordoba, 5000
Novo Nordisk Investigational Site
Salta, A4406CLA
Austria7 sites
Novo Nordisk Investigational Site
Feldkirch, 6807
Novo Nordisk Investigational Site
Innsbruck, 6020
Novo Nordisk Investigational Site
Salzburg, 5020
Novo Nordisk Investigational Site
Vienna, 1030
Novo Nordisk Investigational Site
Vienna, 1090
Novo Nordisk Investigational Site
Vienna, 1130
Novo Nordisk Investigational Site
Vienna, 1170
Spain7 sites
Novo Nordisk Investigational Site
Alcoy, 03803
Novo Nordisk Investigational Site
Alicante, 03010
Novo Nordisk Investigational Site
Barcelona, 08025
Novo Nordisk Investigational Site
Madrid, 28009
Novo Nordisk Investigational Site
Santander, 39008
Novo Nordisk Investigational Site
Seville, 41014
Novo Nordisk Investigational Site
Valencia, 46017
Russia6 sites
Novo Nordisk Investigational Site
Moscow, 101000
Novo Nordisk Investigational Site
Moscow, 127411
Novo Nordisk Investigational Site
Novosibirsk, 630047
Novo Nordisk Investigational Site
Saint Petersburg, 199034
Novo Nordisk Investigational Site
Samara, 443095
Novo Nordisk Investigational Site
Tyumen, 625023
Brazil4 sites
Novo Nordisk Investigational Site
Curitiba, Paraná, 80030-110
Novo Nordisk Investigational Site
Porto Alegre, 90035-170
Novo Nordisk Investigational Site
São Paulo, 01221-900
Novo Nordisk Investigational Site
São Paulo, 04022-002
South Africa4 sites
Novo Nordisk Investigational Site
Durban, KwaZulu-Natal, 4001
Novo Nordisk Investigational Site
Port Elizabeth, Eastern Cape, 6014
Novo Nordisk Investigational Site
Port Elizabeth, Eastern Cape, 6045
Novo Nordisk Investigational Site
Pretoria, Gauteng, 0001
Denmark3 sites
Novo Nordisk Investigational Site
Aalborg, 9000
Novo Nordisk Investigational Site
Aarhus N, 8200
Novo Nordisk Investigational Site
København Ø, 2100
Norway3 sites
Novo Nordisk Investigational Site
Bergen, 5021
Novo Nordisk Investigational Site
Tønsberg, 3116
Novo Nordisk Investigational Site
Trondheim, NO-7030
Ireland2 sites
Novo Nordisk Investigational Site
Dublin, DUBLIN 7
Novo Nordisk Investigational Site
Dublin
About this study
Official 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
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).
- Conditions
- Diabetes, Diabetes Mellitus, Type 1
- Being tested
- insulin detemir, NPH insulin, insulin aspart
- Medical subject headings
- Diabetes Mellitus, Diabetes Mellitus, Type 1
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
insulin detemirDrug
Treat-to-target, dose titration, s.c. (under the skin) injection
NPH insulinDrug
Treat-to-target, dose titration, s.c. (under the skin) injection
insulin aspartDrug
Treat-to-target, dose titration, s.c. (under the skin) injection
| Study group | Role | What they receive |
|---|---|---|
| Insulin detemir | Experimental | 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 Receives: Drug: insulin detemir; Drug: insulin aspart |
| Neutral Protamine Hagedorn (NPH) insulin | Active comparator | 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 Receives: Drug: NPH insulin; Drug: insulin aspart |
What is being measured
The primary outcome is the main question the study is designed to answer.
Glycosylated Haemoglobin (HbA1c) for Full Analysis Set (Pregnant Subjects) at GW 36
Measured: At gestational week (GW) 36
Glycosylated Haemoglobin (HbA1c) for Per Protocol Analysis Set (Pregnant Subjects) at GW 36
Measured: At gestational week (GW) 36
Secondary outcomes (45)
Glycosylated Haemoglobin (HbA1c) During Pregnancy
Measured: 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
Measured: At both Visit P3 (GW 24) and Visit P4 (GW 36)
Fasting Plasma Glucose (FPG)
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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).
Measured: 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).
Measured: 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).
Measured: 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).
Measured: 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).
Measured: 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).
Measured: 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).
Measured: 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).
Measured: 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).
Measured: 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).
Measured: 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).
Measured: 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).
Measured: 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).
Measured: 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).
Measured: 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.
Measured: 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.
Measured: 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
Measured: 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).
Measured: 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)
Measured: 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).
Measured: 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)
Measured: At Delivery (End of Pregnancy) and at Visit P4 (GW 36)
Pregnancy Outcome Safety - Level of Insulin Detemir in Umbilical Cord Blood
Measured: At Delivery
Maternal Safety - Change From Visit P1 in Body Weight During Pregnancy by Visit
Change in the body weight was summarised by treatment.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Follow-Up (6 weeks after delivery)
Safety - Total Daily Insulin Dose During Pregnancy
Measured: 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.
Measured: 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)
Measured: 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)
Measured: At Delivery (End of Pregnancy) and at Visit P4 (GW 36)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 May 2007 (estimated)
- Study startMay 2007
- Primary completionAug 2010
- Study completionAug 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for DiabetesStudies of the same condition, open and under way.
- More trials run by Novo Nordisk A/SThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 470 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novo Nordisk A/S
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Global Clinical Registry (GCR, 1452), Study director, Novo Nordisk A/S
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00474045
- Sponsor's protocol ID
- NN304-1687
- Other IDs
- 2006-004861-33
- Status last verified
- Jan 2017
- First submitted
- 15 May 2007
- Last updated
- 10 Mar 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
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.
PubMed 21557440Mathiesen 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.
PubMed 22851598Hod 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.
PubMed 23617228
Study at a glance
From the registry record, last updated by the sponsor on 10 Mar 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official 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
- ClinicalTrials.gov ID
- NCT00474045
- Acronym / sponsor ID
- NN304-1687
- Conditions
- Diabetes, Diabetes Mellitus, Type 1
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 470 participants (actual)
- Lead sponsor
- Novo Nordisk A/SIndustry (pharma, biotech, devices)
- Study start
- May 2007
- Primary completion
- Aug 2010 (actual)
- Study completion
- Aug 2010 (actual)
- First posted
- 16 May 2007 (estimated)
- Results
- Posted 5 Dec 2011
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Insulin detemir | Experimental | Drug: insulin detemir, Drug: insulin aspartIndividually 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 |
| Neutral Protamine Hagedorn (NPH) insulin | Active comparator | Drug: NPH insulin, Drug: insulin aspartIndividually 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (12 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| insulin detemirTreat-to-target, dose titration, s.c. (under the skin) injection | Drug | Insulin detemir |
| NPH insulinTreat-to-target, dose titration, s.c. (under the skin) injection | Drug | Neutral Protamine Hagedorn (NPH) insulin |
| insulin aspartTreat-to-target, dose titration, s.c. (under the skin) injection | Drug | Insulin detemir, Neutral Protamine Hagedorn (NPH) insulin |
Primary outcome
Glycosylated Haemoglobin (HbA1c) for Full Analysis Set (Pregnant Subjects) at GW 36
Time frame: At gestational week (GW) 36
Glycosylated Haemoglobin (HbA1c) for Per Protocol Analysis Set (Pregnant Subjects) at GW 36
Time frame: At gestational week (GW) 36
45 secondary outcomes
Glycosylated Haemoglobin (HbA1c) During Pregnancy
Time frame: 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
Time frame: At both Visit P3 (GW 24) and Visit P4 (GW 36)
Fasting Plasma Glucose (FPG)
Time frame: 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
Time frame: Visit P3 (GW 24)
8-point Self Monitored Plasma Glucose (SMPG) Profile at GW 36
Time frame: Visit P4 (GW 36)
Maternal Safety - Number of Subjects With Adverse Events (AEs)
Time frame: 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
Time frame: 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
Time frame: Participants were followed during the pregnancy period, an average of 9.6 months
Maternal Safety - Nocturnal Hypoglycaemic Episodes
Time frame: Participants were followed during the pregnancy period, an average of 9.6 months
Maternal Safety - Change in Albumin Serum Level (Biochemistry)
Time frame: Visit P1 (GW 8-12), Follow-Up (FU) Visit (6 weeks after delivery)
Maternal Safety - Change in Alanine Aminotransferase Serum Level (Biochemistry)
Time frame: Visit P1 (GW 8-12), Follow-Up (FU) Visit (6 weeks after delivery)
Maternal Safety - Change in Alkaline Phosphatase Serum Level (Biochemistry)
Time frame: Visit P1 (GW 8-12), Follow-Up (FU) Visit (6 weeks after delivery)
Maternal Safety - Change in Creatinine Serum Level (Biochemistry)
Time frame: Visit P1 (GW 8-12), Follow-Up (FU) Visit (6 weeks after delivery)
Maternal Safety - Change in Lactate Dehydrogenase Serum Level (Biochemistry)
Time frame: Visit P1 (GW 8-12), Follow-Up (FU) Visit (6 weeks after delivery)
Maternal Safety - Change in Potassium Serum Level (Biochemistry)
Time frame: Visit P1 (GW 8-12), Follow-Up (FU) Visit (6 weeks after delivery)
Maternal Safety - Change in Sodium Serum Level (Biochemistry)
Time frame: Visit P1 (GW 8-12), Follow-Up (FU) Visit (6 weeks after delivery)
Maternal Safety - Change in Total Protein Serum Level (Biochemistry)
Time frame: Visit P1 (GW 8-12), Follow-Up (FU) Visit (6 weeks after delivery)
Maternal Safety - Change in Haemoglobin Level (Haematology)
Time frame: Visit P1 (GW 8-12), Follow-Up (FU) Visit (6 weeks after delivery)
Maternal Safety - Change in Leukocytes Level (Haematology)
Time frame: Visit P1 (GW 8-12), Follow-Up (FU) Visit (6 weeks after delivery)
Maternal Safety - Change in Thrombocytes Level (Haematology)
Time frame: Visit P1 (GW 8-12), Follow-Up (FU) Visit (6 weeks after delivery)
Maternal Safety - Change in Urine Albumin Level (Urinalysis)
Time frame: Visit P1 (GW 8-12), Follow-Up (FU) Visit (6 weeks after delivery)
Maternal Safety - Change in Albumin/Creatinine Ratio (Urinalysis)
Time frame: Visit P1 (GW 8-12), Follow-Up (FU) Visit (6 weeks after delivery)
Maternal Safety - Change in Urine N (Creatinine) (Urinalysis)
Time frame: Visit P1 (GW 8-12), Follow-Up (FU) Visit (6 weeks after delivery)
Maternal Safety - Change in Insulin Detemir Specific Antibodies
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: At Delivery (End of Pregnancy)
Pregnancy Outcome Safety - Level of Aspart Specific Antibodies (AB) in Umbilical Cord Blood
Time frame: At Delivery (End of Pregnancy)
Pregnancy Outcome Safety - Level of Cross-Reacting Antibodies (AB) in Umbilical Cord Blood
Time frame: At Delivery (End of Pregnancy)
Ratio Between Detemir Specific Antibodies in Cord Blood and Maternal Antibodies
Time frame: At Delivery (End of Pregnancy) and at Visit P4 (GW 36)
Pregnancy Outcome Safety - Level of Insulin Detemir in Umbilical Cord Blood
Time frame: At Delivery
Maternal Safety - Change From Visit P1 in Body Weight During Pregnancy by Visit
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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)
Time frame: Follow-Up (6 weeks after delivery)
Maternal Safety - Acceleration of Retinopathy in Any Eye
Time frame: From GW 8-12 (Visit P1) to Follow-Up (6 weeks after delivery)
Maternal Safety - Acceleration of Nephropathy
Time frame: From GW 8-12 (Visit P1) to Follow-Up (6 weeks after delivery)
Maternal Safety - Mode of Delivery
Time frame: At Delivery Visit
Pregnancy Outcome at Delivery
Time frame: Delivery Visit
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Mar 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 21557440Mathiesen 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.
- Results publication: PubMed 22851598Mathiesen 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.
- Results publication: PubMed 23617228Hod 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.
- Clinical Trials at Novo NordiskLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Global Clinical Registry (GCR, 1452) study director
Novo Nordisk A/S
98 sites in 17 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing insulin detemir, NPH insulin and insulin aspart in people with Diabetes and Diabetes Mellitus, Type 1, run by Novo Nordisk A/S at 98 sites in 17 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 10 Mar 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 98 sites in United Kingdom, Canada, France, Australia, Poland and 12 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 5 Dec 2011). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Glycosylated Haemoglobin (HbA1c) for Full Analysis Set (Pregnant Subjects) at GW 36 (time frame: At gestational week (GW) 36). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00474045, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Mar 2017.