Phase 3
Completed N=470
Efficacy and Safety of Insulin Detemir Versus Neutral Protamine Hagedorn (NPH) Insulin in Pregnant Women With Type 1 Diabetes
Diabetes · Diabetes Mellitus, Type 1
Source: ClinicalTrials.gov NCT00474045 ↗
Enrolled (actual)
470
Serious AEs
35.5%
Results posted
Dec 2011
Primary outcomePrimary: Glycosylated Haemoglobin (HbA1c) for Full Analysis Set (Pregnant Subjects) at GW 36 — 6.27; 6.33 Percent (%) glycosylated haemoglobin — p=0.400
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).
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Glycosylated Haemoglobin (HbA1c) for Full Analysis Set (Pregnant Subjects) at GW 36 |
6.27; 6.33 | 0.400 |
| PRIMARY Glycosylated Haemoglobin (HbA1c) for Per Protocol Analysis Set (Pregnant Subjects) at GW 36 |
6.22; 6.37 | 0.122 |
| SECONDARY Glycosylated Haemoglobin (HbA1c) During Pregnancy |
6.6; 6.8; 6.3; 6.5; 6; 6.1 | — |
| SECONDARY Subjects Reaching HbA1c at or Below 6.0% Both at GW 24 and GW 36 |
57; 46 | — |
| SECONDARY Fasting Plasma Glucose (FPG) |
5.0; 5.8; 5.0; 5.7; 5.2; 6.3 | — |
| SECONDARY 8-point Self-monitored Plasma Glucose (SMPG) Profile at GW 24 |
6.4; 7.3; 7.7; 8.0; 6.1; 6.7 | — |
| SECONDARY 8-point Self Monitored Plasma Glucose (SMPG) Profile at GW 36 |
6; 6.3; 7.4; 7.5; 5.9; 6.1 | — |
| SECONDARY Maternal Safety - Number of Subjects With Adverse Events (AEs) |
138; 141; 61; 49; 38; 32 | — |
| SECONDARY Safety in Children - Number of Subjects (Foetuses and Newborns) With Adverse Events |
56; 55; 36; 32; 15; 12 | — |
| SECONDARY Maternal Safety - Hypoglycaemic Episodes |
9496; 9453; 8045; 7810 | — |
| SECONDARY Maternal Safety - Nocturnal Hypoglycaemic Episodes |
1451; 1643 | — |
| SECONDARY Maternal Safety - Change in Albumin Serum Level (Biochemistry) |
4.05; 4.04; 4.19; 4.12; 0.13; 0.09 | — |
| SECONDARY Maternal Safety - Change in Alanine Aminotransferase Serum Level (Biochemistry) |
16.12; 17.97; 27.06; 26.16; 10.88; 8.16 | — |
| SECONDARY Maternal Safety - Change in Alkaline Phosphatase Serum Level (Biochemistry) |
52.64; 53.88; 90.17; 92.96; 37.39; 39.51 | — |
| SECONDARY Maternal Safety - Change in Creatinine Serum Level (Biochemistry) |
52.04; 54.01; 62.98; 66.57; 11.18; 12.52 | — |
| SECONDARY Maternal Safety - Change in Lactate Dehydrogenase Serum Level (Biochemistry) |
145.1; 144.1; 167.5; 169.5; 21.82; 25.46 | — |
| SECONDARY Maternal Safety - Change in Potassium Serum Level (Biochemistry) |
4.13; 4.12; 4.30; 4.31; 0.15; 0.20 | — |
| SECONDARY Maternal Safety - Change in Sodium Serum Level (Biochemistry) |
138.0; 137.8; 141.6; 141.2; 3.59; 3.36 | — |
| SECONDARY Maternal Safety - Change in Total Protein Serum Level (Biochemistry) |
6.84; 6.89; 7.08; 7.11; 0.24; 0.22 | — |
| SECONDARY Maternal Safety - Change in Haemoglobin Level (Haematology) |
7.64; 7.64; 7.81; 7.69; 0.16; 0.05 | — |
| SECONDARY Maternal Safety - Change in Leukocytes Level (Haematology) |
8.01; 8.2; 6.68; 6.55; -1.36; -1.65 | — |
| SECONDARY Maternal Safety - Change in Thrombocytes Level (Haematology) |
245.3; 247.2; 270.6; 263.1; 24.25; 16.16 | — |
| SECONDARY Maternal Safety - Change in Urine Albumin Level (Urinalysis) |
0.01; 0.01; 0.02; 0.03; 0.01; 0.02 | — |
| SECONDARY Maternal Safety - Change in Albumin/Creatinine Ratio (Urinalysis) |
0.82; 0.85; 2.65; 4.81; 1.88; 4.07 | — |
| SECONDARY Maternal Safety - Change in Urine N (Creatinine) (Urinalysis) |
114.8; 103.1; 106.2; 98.61; -6.62; -6.34 | — |
| SECONDARY Maternal Safety - Change in Insulin Detemir Specific Antibodies |
1.13; 1.09; 1.36; 1.25; 0.04; 0.09 | — |
| SECONDARY Maternal Safety - Change in Insulin Aspart Specific Antibodies |
0.44; 0.46; 0.43; 0.36; -0.12; -0.21 | — |
| SECONDARY Maternal Safety - Change in Insulin Detemir/Insulin Aspart Cross Reacting Antibodies |
5.21; 5.36; 5.40; 4.28; -0.43; -1.12 | — |
| SECONDARY Pregnancy Outcome Safety - Level of Detemir Specific Antibodies (AB) in Umbilical Cord Blood |
1.31; 0.90 | — |
| SECONDARY Pregnancy Outcome Safety - Level of Aspart Specific Antibodies (AB) in Umbilical Cord Blood |
0.38; 0.32 | — |
| SECONDARY Pregnancy Outcome Safety - Level of Cross-Reacting Antibodies (AB) in Umbilical Cord Blood |
5.99; 4.12 | — |
| SECONDARY Ratio Between Detemir Specific Antibodies in Cord Blood and Maternal Antibodies |
1.10; 0.77 | — |
| SECONDARY Pregnancy Outcome Safety - Level of Insulin Detemir in Umbilical Cord Blood |
25.00 | — |
| SECONDARY Maternal Safety - Change From Visit P1 in Body Weight During Pregnancy by Visit |
67.8; 69.2; 1.0; 1.4; 5.6; 6.0 | — |
| SECONDARY Maternal Safety - Change From Visit P1 in Systolic Blood Pressure During Pregnancy and at Follow-Up by Visit |
114.1; 116.2; 0.8; -2.8; -0.7; -1.6 | — |
| SECONDARY Maternal Safety - Change From Visit P1 in Diastolic Blood Pressure During Pregnancy and at Follow-Up by Visit |
70.5; 70.7; -0.2; -0.5; -1.6; -1.2 | — |
| SECONDARY Maternal Safety - Change From Visit P1 in Pulse During Pregnancy and at Follow-Up |
77.4; 76.8; 1.5; 2.2; 3.5; 4.5 | — |
| SECONDARY Maternal Safety - Electrocardiogram (ECG) |
0; 0 | — |
| SECONDARY Maternal Safety - Acceleration of Retinopathy in Any Eye |
12; 14; 120; 120; 20; 24 | — |
| SECONDARY Maternal Safety - Acceleration of Nephropathy |
2; 1 | — |
| SECONDARY Maternal Safety - Mode of Delivery |
19; 28; 39; 36; 76; 80 | — |
| SECONDARY Pregnancy Outcome at Delivery |
128; 136; 10; 8; 1; 1 | — |
| SECONDARY Pregnancy Outcome at Follow-Up |
128; 135; 10; 8; 1; 1 | — |
| SECONDARY Safety - Total Daily Insulin Dose During Pregnancy |
0.73; 0.74; 0.85; 0.84; 1.17; 1.05 | — |
| SECONDARY Safety - Composite Pregnancy Outcome |
3; 1; 59; 73; 39; 45 | — |
| SECONDARY Ratio Between Aspart Specific Antibodies in Cord Blood and Maternal Antibodies |
0.84; 0.64 | — |
| SECONDARY Ratio Between Cross-reacting Antibodies in Cord Blood and Maternal Antibodies |
1.29; 0.90 | — |
Eligibility Criteria
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
Data sourced from ClinicalTrials.gov (NCT00474045). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.