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
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 470
- 试验地点
- 1
- 主要终点
- Glycosylated Haemoglobin (HbA1c) for Full Analysis Set (Pregnant Subjects) at GW 36
研究概览
简要总结
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).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
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
干预措施: insulin detemir (Drug)
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
干预措施: insulin aspart (Drug)
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
干预措施: NPH insulin (Drug)
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
干预措施: insulin aspart (Drug)
结局指标
主要结局
Glycosylated Haemoglobin (HbA1c) for Full Analysis Set (Pregnant Subjects) at GW 36
时间窗: At gestational week (GW) 36
Glycosylated Haemoglobin (HbA1c) for Per Protocol Analysis Set (Pregnant Subjects) at GW 36
时间窗: At gestational week (GW) 36
次要结局
- Maternal Safety - Hypoglycaemic Episodes(Participants were followed during the pregnancy period, an average of 9.6 months)
- Glycosylated Haemoglobin (HbA1c) During Pregnancy(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))
- 8-point Self-monitored Plasma Glucose (SMPG) Profile at GW 24(Visit P3 (GW 24))
- 8-point Self Monitored Plasma Glucose (SMPG) Profile at GW 36(Visit P4 (GW 36))
- Maternal Safety - Change in Albumin Serum Level (Biochemistry)(Visit P1 (GW 8-12), Follow-Up (FU) Visit (6 weeks after delivery))
- Maternal Safety - Change in Total Protein Serum Level (Biochemistry)(Visit P1 (GW 8-12), Follow-Up (FU) Visit (6 weeks after delivery))
- Maternal Safety - Change in Haemoglobin Level (Haematology)(Visit P1 (GW 8-12), Follow-Up (FU) Visit (6 weeks after delivery))
- Maternal Safety - Number of Subjects With Adverse Events (AEs)(Participants were followed during the pregnancy period, an average of 9.6 months)
- Maternal Safety - Change in Alanine Aminotransferase Serum Level (Biochemistry)(Visit P1 (GW 8-12), Follow-Up (FU) Visit (6 weeks after delivery))
- Maternal Safety - Change in Alkaline Phosphatase Serum Level (Biochemistry)(Visit P1 (GW 8-12), Follow-Up (FU) Visit (6 weeks after delivery))
- Maternal Safety - Change in Creatinine Serum Level (Biochemistry)(Visit P1 (GW 8-12), Follow-Up (FU) Visit (6 weeks after delivery))
- Maternal Safety - Change in Albumin/Creatinine Ratio (Urinalysis)(Visit P1 (GW 8-12), Follow-Up (FU) Visit (6 weeks after delivery))
- Maternal Safety - Change in Insulin Detemir/Insulin Aspart Cross Reacting Antibodies(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.)
- Ratio Between Detemir Specific Antibodies in Cord Blood and Maternal Antibodies(At Delivery (End of Pregnancy) and at Visit P4 (GW 36))
- Pregnancy Outcome Safety - Level of Insulin Detemir in Umbilical Cord Blood(At Delivery)
- Maternal Safety - Change in Leukocytes Level (Haematology)(Visit P1 (GW 8-12), Follow-Up (FU) Visit (6 weeks after delivery))
- Pregnancy Outcome Safety - Level of Cross-Reacting Antibodies (AB) in Umbilical Cord Blood(At Delivery (End of Pregnancy))
- Maternal Safety - Change From Visit P1 in Body Weight During Pregnancy by Visit(Visit P1 (GW (8-12), Visit P2 (GW 14), Visit P3 (GW 24), Visit P4 (GW 36))
- Pregnancy Outcome at Delivery(Delivery Visit)
- Pregnancy Outcome at Follow-Up(Follow-Up (6 weeks after delivery))
- Safety - Composite Pregnancy Outcome(End of Pregnancy)
- Ratio Between Aspart Specific Antibodies in Cord Blood and Maternal Antibodies(At Delivery (End of Pregnancy) and at Visit P4 (GW 36))
- Subjects Reaching HbA1c at or Below 6.0% Both at GW 24 and GW 36(At both Visit P3 (GW 24) and Visit P4 (GW 36))
- Fasting Plasma Glucose (FPG)(During the pregnancy period [Visit P1 (GW 8-12), Visit P2 (GW 14), Visit P3 (GW 24), Visit P4 (GW 36)])
- Safety in Children - Number of Subjects (Foetuses and Newborns) With Adverse Events(Foetuses/Newborns were followed during the pregnancy period, an average of 9.6 months and Follow-Up period (6 weeks after delivery))
- Maternal Safety - Nocturnal Hypoglycaemic Episodes(Participants were followed during the pregnancy period, an average of 9.6 months)
- Maternal Safety - Change in Lactate Dehydrogenase Serum Level (Biochemistry)(Visit P1 (GW 8-12), Follow-Up (FU) Visit (6 weeks after delivery))
- Maternal Safety - Change in Potassium Serum Level (Biochemistry)(Visit P1 (GW 8-12), Follow-Up (FU) Visit (6 weeks after delivery))
- Maternal Safety - Change in Sodium Serum Level (Biochemistry)(Visit P1 (GW 8-12), Follow-Up (FU) Visit (6 weeks after delivery))
- Maternal Safety - Change in Thrombocytes Level (Haematology)(Visit P1 (GW 8-12), Follow-Up (FU) Visit (6 weeks after delivery))
- Maternal Safety - Change in Urine Albumin Level (Urinalysis)(Visit P1 (GW 8-12), Follow-Up (FU) Visit (6 weeks after delivery))
- Maternal Safety - Change in Urine N (Creatinine) (Urinalysis)(Visit P1 (GW 8-12), Follow-Up (FU) Visit (6 weeks after delivery))
- Maternal Safety - Change in Insulin Detemir Specific Antibodies(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 From Visit P1 in Systolic Blood Pressure During Pregnancy and at Follow-Up by Visit(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 in Insulin Aspart Specific Antibodies(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(At Delivery (End of Pregnancy))
- Maternal Safety - Change From Visit P1 in Pulse During Pregnancy and at Follow-Up(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 - Acceleration of Retinopathy in Any Eye(From GW 8-12 (Visit P1) to Follow-Up (6 weeks after delivery))
- Maternal Safety - Mode of Delivery(At Delivery Visit)
- Pregnancy Outcome Safety - Level of Aspart Specific Antibodies (AB) in Umbilical Cord Blood(At Delivery (End of Pregnancy))
- Maternal Safety - Change From Visit P1 in Diastolic Blood Pressure During Pregnancy and at Follow-Up by Visit(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))
- Ratio Between Cross-reacting Antibodies in Cord Blood and Maternal Antibodies(At Delivery (End of Pregnancy) and at Visit P4 (GW 36))
- Maternal Safety - Electrocardiogram (ECG)(Follow-Up (6 weeks after delivery))
- Maternal Safety - Acceleration of Nephropathy(From GW 8-12 (Visit P1) to Follow-Up (6 weeks after delivery))
- Safety - Total Daily Insulin Dose During Pregnancy(Visit P2 (GW 14), Visit P3 (GW 24), Visit P4 (GW 36), Follow-Up (6 weeks after delivery))