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Completed

NCT Number: NCT00474045

Efficacy and Safety of Insulin Detemir Versus Neutral Protamine Hagedorn (NPH) Insulin in 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).

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Key information

Conditions

Diabetes Autoimmune Diseases Diabetes Mellitus Diabetes Mellitus, Type 1 Endocrine System Diseases Glucose Metabolism Disorders Immune System Diseases Metabolic Diseases Nutritional and Metabolic Diseases

Age range

18 year and older

Sex eligibility

Female

Study type

Interventional

Phase

Phase 3

Primary location

Novo Nordisk Investigational Site, Buenos Aires, Argentina

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

insulin detemir

Drug

Treat-to-target, dose titration, s.c. (under the skin) injection

NPH insulin

Drug

Treat-to-target, dose titration, s.c. (under the skin) injection

insulin aspart

Drug

Treat-to-target, dose titration, s.c. (under the skin) injection

Primary outcomes

  1. Glycosylated Haemoglobin (HbA1c) for Full Analysis Set (Pregnant Subjects) at GW 36

    Time frame: At gestational week (GW) 36

  2. Glycosylated Haemoglobin (HbA1c) for Per Protocol Analysis Set (Pregnant Subjects) at GW 36

    Time frame: At gestational week (GW) 36

Secondary outcomes

  1. 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)

  2. 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)

  3. 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)]

  4. 8-point Self-monitored Plasma Glucose (SMPG) Profile at GW 24

    Time frame: Visit P3 (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.

  5. 8-point Self Monitored Plasma Glucose (SMPG) Profile at GW 36

    Time frame: Visit P4 (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.

  6. Maternal Safety - Number of Subjects With Adverse Events (AEs)

    Time frame: Participants were followed during the pregnancy period, an average of 9.6 months

    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.

  7. 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)

    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.

  8. Maternal Safety - Hypoglycaemic Episodes

    Time frame: Participants were followed during the pregnancy period, an average of 9.6 months

    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.

  9. Maternal Safety - Nocturnal Hypoglycaemic Episodes

    Time frame: Participants were followed during the pregnancy period, an average of 9.6 months

    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.

  10. Maternal Safety - Change in Albumin Serum Level (Biochemistry)

    Time frame: Visit P1 (GW 8-12), Follow-Up (FU) Visit (6 weeks after delivery)

    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).

  11. Maternal Safety - Change in Alanine Aminotransferase Serum Level (Biochemistry)

    Time frame: Visit P1 (GW 8-12), Follow-Up (FU) Visit (6 weeks after delivery)

    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).

  12. Maternal Safety - Change in Alkaline Phosphatase Serum Level (Biochemistry)

    Time frame: Visit P1 (GW 8-12), Follow-Up (FU) Visit (6 weeks after delivery)

    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).

  13. Maternal Safety - Change in Creatinine Serum Level (Biochemistry)

    Time frame: Visit P1 (GW 8-12), Follow-Up (FU) Visit (6 weeks after delivery)

    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).

  14. Maternal Safety - Change in Lactate Dehydrogenase Serum Level (Biochemistry)

    Time frame: Visit P1 (GW 8-12), Follow-Up (FU) Visit (6 weeks after delivery)

    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).

  15. Maternal Safety - Change in Potassium Serum Level (Biochemistry)

    Time frame: Visit P1 (GW 8-12), Follow-Up (FU) Visit (6 weeks after delivery)

    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).

  16. Maternal Safety - Change in Sodium Serum Level (Biochemistry)

    Time frame: Visit P1 (GW 8-12), Follow-Up (FU) Visit (6 weeks after delivery)

    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).

  17. Maternal Safety - Change in Total Protein Serum Level (Biochemistry)

    Time frame: Visit P1 (GW 8-12), Follow-Up (FU) Visit (6 weeks after delivery)

    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).

  18. Maternal Safety - Change in Haemoglobin Level (Haematology)

    Time frame: Visit P1 (GW 8-12), Follow-Up (FU) Visit (6 weeks after delivery)

    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).

  19. Maternal Safety - Change in Leukocytes Level (Haematology)

    Time frame: Visit P1 (GW 8-12), Follow-Up (FU) Visit (6 weeks after delivery)

    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).

  20. Maternal Safety - Change in Thrombocytes Level (Haematology)

    Time frame: Visit P1 (GW 8-12), Follow-Up (FU) Visit (6 weeks after delivery)

    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).

  21. Maternal Safety - Change in Urine Albumin Level (Urinalysis)

    Time frame: Visit P1 (GW 8-12), Follow-Up (FU) Visit (6 weeks after delivery)

    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).

  22. Maternal Safety - Change in Albumin/Creatinine Ratio (Urinalysis)

    Time frame: Visit P1 (GW 8-12), Follow-Up (FU) Visit (6 weeks after delivery)

    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).

  23. Maternal Safety - Change in Urine N (Creatinine) (Urinalysis)

    Time frame: Visit P1 (GW 8-12), Follow-Up (FU) Visit (6 weeks after delivery)

    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).

  24. 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.

    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.

  25. 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.

    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.

  26. 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.

    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

  27. Pregnancy Outcome Safety - Level of Detemir Specific Antibodies (AB) in Umbilical Cord Blood

    Time frame: At Delivery (End of Pregnancy)

    Antibodies were measured in a subtraction radioimmunoassay and expressed as antibody bound tracer relative to the total amount of tracer (%B/T).

  28. Pregnancy Outcome Safety - Level of Aspart Specific Antibodies (AB) in Umbilical Cord Blood

    Time frame: At Delivery (End of Pregnancy)

    Antibodies were measured in a subtraction radioimmunoassay and expressed as antibody bound tracer relative to the total amount of tracer (%B/T)

  29. Pregnancy Outcome Safety - Level of Cross-Reacting Antibodies (AB) in Umbilical Cord Blood

    Time frame: At Delivery (End of Pregnancy)

    Antibodies were measured in a subtraction radioimmunoassay and expressed as antibody bound tracer relative to the total amount of tracer (%B/T).

  30. Ratio Between Detemir Specific Antibodies in Cord Blood and Maternal Antibodies

    Time frame: At Delivery (End of Pregnancy) and at Visit P4 (GW 36)

    Cord blood (at delivery) vs. Maternal Blood at Visit P4 (GW 36)

  31. Pregnancy Outcome Safety - Level of Insulin Detemir in Umbilical Cord Blood

    Time frame: At Delivery

  32. 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)

    Change in the body weight was summarised by treatment.

  33. 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)

    Change in the systolic blood pressure was summarised by treatment.

  34. 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)

    Change in the diastolic blood pressure was summarised by treatment.

  35. 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)

    Change in the pulse was summarised by treatment.

  36. Maternal Safety - Electrocardiogram (ECG)

    Time frame: Follow-Up (6 weeks after delivery)

    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.

  37. Maternal Safety - Acceleration of Retinopathy in Any Eye

    Time frame: From GW 8-12 (Visit P1) to Follow-Up (6 weeks after delivery)

    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.

  38. Maternal Safety - Acceleration of Nephropathy

    Time frame: From GW 8-12 (Visit P1) to Follow-Up (6 weeks after delivery)

    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.

  39. Maternal Safety - Mode of Delivery

    Time frame: At Delivery Visit

    Non-Planned Caesarean Section is a procedure which takes place ≤8h prior to delivery. Planned Caesarean Section takes place >8h prior to delivery.

  40. Pregnancy Outcome at Delivery

    Time frame: Delivery Visit

    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.

  41. Pregnancy Outcome at Follow-Up

    Time frame: Follow-Up (6 weeks after delivery)

    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.

  42. Safety - Total Daily Insulin Dose During Pregnancy

    Time frame: Visit P2 (GW 14), Visit P3 (GW 24), Visit P4 (GW 36), Follow-Up (6 weeks after delivery)

  43. Safety - Composite Pregnancy Outcome

    Time frame: End of Pregnancy

    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.

  44. Ratio Between Aspart Specific Antibodies in Cord Blood and Maternal Antibodies

    Time frame: At Delivery (End of Pregnancy) and at Visit P4 (GW 36)

    Cord blood (at delivery) vs. Maternal Blood at Visit P4 (GW 36)

  45. Ratio Between Cross-reacting Antibodies in Cord Blood and Maternal Antibodies

    Time frame: At Delivery (End of Pregnancy) and at Visit P4 (GW 36)

    Cord blood (at delivery) vs. Maternal Blood at Visit P4 (GW 36)

Sponsors and collaborators

Lead sponsor

Novo Nordisk A/S

Industry

Registry information

Official study 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

Important dates

Study start
2007
Primary completion
2010
Study completion
2010
First posted
May 16, 2007
Registry last updated
Mar 10, 2017

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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