Clinical trial NCT03377699: Research Study Comparing Insulin Degludec to Insulin Detemir, Together With Insulin Aspart, in Pregnant Women With Type 1 Diabetes
Official title: A Trial Comparing the Effect and Safety of Insulin Degludec Versus Insulin Detemir, Both in Combination With Insulin Aspart, in the Treatment of Pregnant Women With Type 1 Diabetes
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Diabetes
Diabetes Mellitus, Type 1
Lead sponsor: Novo Nordisk A/S
Sponsor class: INDUSTRY
First posted: 2017-12-19
Enrollment: 225
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The investigators are doing this study to see the effect of insulin degludec in pregnant women with type 1 diabetes, and if it is safe to use. In this study the medicine insulin degludec is compared to another medicine called insulin detemir. Participants will either get insulin degludec or insulin detemir and take it together with a medicine called insulin aspart - which treatment participants get is decided by chance. Participants will get pre-filled insulin pens. Participants will need to take blood sugar measurements several times a day. The study will last between 10 and 25 months depending on whether participants are already pregnant when they join the study. The number of visits and the tests ( for example blood and urine samples and ultrasound scans) the participants will have also depends on whether they are pregnant at study start.


Eligibility criteria: Inclusion Criteria: - Female, age at least 18 years at the time of signing informed consent - Diagnosed with type 1 diabetes mellitus for at least 1 year prior to the day of screening - Treated with multiple daily subcutaneous insulin injections or continuous subcutaneous insulin infusion (CSII) or inhaled insulin for at least 90 days prior to the day of screening - The subject is planning to become pregnant within 12 months from randomisation and willing to undertake pre-pregnancy counselling or the subject is pregnant with an intrauterine singleton living foetus (gestational week 8 to 13 (+6 days)) without any observed anomalies at randomisation, confirmed by an ultrasound scan - HbA1c at screening below or equal to 8.0% (64 mmol/mol) by central laboratory Exclusion Criteria: - Treatment with any medication for the indication of diabetes or obesity other than stated in the inclusion criteria within the past 90 days prior to the day of screening - Pregnant and having proteinuria as evaluated by urine protein-to-creatinine ratio above or equal to 300 mg/g in urine sample measured at screening - Subject being treated or became pregnant with assistance of in vitro fertilisation or other medical infertility treatment - Receipt of any concomitant medication contraindicated in pregnancy according to local label within 28 days before screening and between screening and randomisation for non-pregnant subjects and 28 days before conception and between conception and randomisation for pregnant subjects - Proliferative retinopathy or maculopathy requiring acute treatment. Verified by fundus photography or pharmacologically dilated fundoscopy performed within the past 90 days prior to randomisation for non-pregnant subjects or within 28 days prior to randomisation for pregnant subjects. - History of severe hyperemesis gravidarum (requiring hospitalisation)

Primary outcomes:
measure: Last Planned Glycosylated Haemoglobin (HbA1c) Prior to Delivery
timeFrame: From GW 16 to GW 36
Secondary outcomes:
measure: Number of Participants With HbA1c Below or Equal to 6.0% [42 Millimoles Per Mole (mmol/Mol)] From Last Planned HbA1c Prior to Delivery (Yes/no)
timeFrame: From GW 16 to GW 36
measure: Number of Participants With HbA1c Below or Equal to 6.5% (48 mmol/Mol) From Last Planned HbA1c Prior to Delivery (Yes/no)
timeFrame: From GW 16 to GW 36
measure: Last Planned Average Post-prandial Glucose Prior to Delivery (Average of Three Main Meals)
timeFrame: From GW 16 to GW 36
measure: Last Planned Fasting Plasma Glucose Prior to Delivery
timeFrame: From GW 16 to GW 36
measure: Number of Hypoglycaemic Episodes During the Pregnancy Period
timeFrame: From the first day of pregnancy (date of conception) or randomisation to delivery (maximum 23 months)
measure: Number of Participants Who Developed Sight-threatening Retinopathy (Defined as Proliferative Retinopathy or Maculopathy) From Pregnancy Baseline to the End of Treatment (Yes/no)
timeFrame: From pregnancy baseline (corresponding to GW 8-13) to end of treatment (28 days after delivery)
measure: Number of Participants Who Developed Sight-threatening Retinopathy Defined as Proliferative Retinopathy or Maculopathy From Treatment Baseline to the End of Treatment (Yes/no)
timeFrame: From treatment baseline (week 0) to end of treatment (28 days after delivery)
measure: Number of Adverse Events During Pregnancy Period
timeFrame: From the first day of pregnancy (date of conception) or randomisation to delivery (maximum 23 months)
measure: Number of Participants With Pre-eclampsia Defined as New-onset Hypertension Occurring From Gestational Week 20 to Delivery and Simultaneous Proteinuria or Presence of Eclampsia, HELLP Syndrome, or Other Severe Organ Involvement (Yes/no)
timeFrame: From GW 20 to delivery
measure: Number of Participants With Different Modes of Delivery e.g. Vaginal, Operative Vaginal, Planned Caesarean Section or Unplanned Caesarean Section Delivery
timeFrame: At birth
measure: Change in Body Weight From Pregnancy Baseline to Last Planned Visit Prior to Delivery
timeFrame: From pregnancy baseline (corresponding to gestational week 8-13) to last planned visit before delivery (last weight recording before given birth)
measure: Birth Weight for Live Birth Infants
timeFrame: At birth
measure: Birth Weight Standard Deviation (SD) Score for Live Birth Infants
timeFrame: At birth
measure: Number of Live Born Infants With Birth Weight < 10th Percentile for Gestational Age and Sex (Local References) (Yes/no)
timeFrame: At birth
measure: Number of Live Born Infants With Birth Weight > 90th Percentile for Gestational Age and Sex (Local References) [Yes/no]
timeFrame: At birth
measure: Number of Participants With Pre-term Delivery
timeFrame: At birth
measure: Number of Participants With Early Foetal Death (Delivery Before 20 Completed GWs) (Yes/no)
timeFrame: At birth
measure: Number of Participants Who Had Perinatal Mortality (Death of Foetus/Infant ) (Yes/no)
timeFrame: Between at least 20 completed GWs before delivery and before 7 completed days after delivery
measure: Number of Participants Who Had Neonatal Mortality (Death of Infant) (Yes/no)
timeFrame: Between at least 7 completed days after delivery and before 28 completed days after delivery
measure: Number of Participants With Presence of Major Abnormalities (Classified According to European Concerted Action on Congenital Anomalies and Twins (EUROCAT)) in Their Foetus/Infants
timeFrame: At birth
measure: Number of Participants With Live Born Infants (Yes/no)
timeFrame: At birth
measure: Number of Adverse Events in the Infant
timeFrame: From delivery to final follow-up 30 days after delivery
measure: Neonatal Hypoglycaemic Episodes Defined as Plasma Glucose Below or Equal to 1.7 mmol/L (31 mg/dL) or Below or Equal to 2.5 mmol/L (45 mg/dl) (Yes/no)
timeFrame: During between 24 and 48 hours after birth
Other outcomes:
Locations:
city: Caba
country: Argentina
facility: Novo Nordisk Investigational Site
city: Caba
country: Argentina
facility: Novo Nordisk Investigational Site
city: Caba
country: Argentina
facility: Novo Nordisk Investigational Site
city: Córdoba
country: Argentina
facility: Novo Nordisk Investigational Site
city: Mendoza
country: Argentina
facility: Novo Nordisk Investigational Site
city: Salta
country: Argentina
facility: Novo Nordisk Investigational Site
city: Blacktown
country: Australia
facility: Novo Nordisk Investigational Site
state: New South Wales
city: Campbelltown
country: Australia
facility: Novo Nordisk Investigational Site
state: New South Wales
city: St Leonards
country: Australia
facility: Novo Nordisk Investigational Site
state: New South Wales
city: Ipswich
country: Australia
facility: Novo Nordisk Investigational Site
state: Queensland
city: Elizabeth Vale
country: Australia
facility: Novo Nordisk Investigational Site
state: South Australia
city: Box Hill
country: Australia
facility: Novo Nordisk Investigational Site
state: Victoria
city: Parkville
country: Australia
facility: Novo Nordisk Investigational Site
state: Victoria
city: Graz
country: Austria
facility: Novo Nordisk Investigational Site
city: Innsbruck
country: Austria
facility: Novo Nordisk Investigational Site
city: Wien
country: Austria
facility: Novo Nordisk Investigational Site
city: Wien
country: Austria
facility: Novo Nordisk Investigational Site
city: Wien
country: Austria
facility: Novo Nordisk Investigational Site
city: Goiânia
country: Brazil
facility: Novo Nordisk Investigational Site
state: Goias
city: Curitiba
country: Brazil
facility: Novo Nordisk Investigational Site
state: Parana
city: Porto Alegre
country: Brazil
facility: Novo Nordisk Investigational Site
state: Rio Grande Do Sul
city: São Paulo
country: Brazil
facility: Novo Nordisk Investigational Site
state: Sao Paulo
city: São Paulo
country: Brazil
facility: Novo Nordisk Investigational Site
state: Sao Paulo
city: Ribeirao Preto
country: Brazil
facility: Novo Nordisk Investigational Site
city: Edmonton
country: Canada
facility: Novo Nordisk Investigational Site
state: Alberta
city: Vancouver
country: Canada
facility: Novo Nordisk Investigational Site
state: British Columbia
city: St John's
country: Canada
facility: Novo Nordisk Investigational Site
state: Newfoundland and Labrador
city: Halifax
country: Canada
facility: Novo Nordisk Investigational Site
state: Nova Scotia
city: Cambridge
country: Canada
facility: Novo Nordisk Investigational Site
state: Ontario
city: London
country: Canada
facility: Novo Nordisk Investigational Site
state: Ontario
city: Toronto
country: Canada
facility: Novo Nordisk Investigational Site
state: Ontario
city: Toronto
country: Canada
facility: Novo Nordisk Investigational Site
state: Ontario
city: PQ
country: Canada
facility: Novo Nordisk Investigational Site
state: Quebec
city: Zagreb
country: Croatia
facility: Novo Nordisk Investigational Site
city: Aarhus N
country: Denmark
facility: Novo Nordisk Investigational Site
city: København ø
country: Denmark
facility: Novo Nordisk Investigational Site
city: Athens
country: Greece
facility: Novo Nordisk Investigational Site
city: Athens
country: Greece
facility: Novo Nordisk Investigational Site
city: Larissa
country: Greece
facility: Novo Nordisk Investigational Site
city: Nea Efkarpia - Thessaloniki
country: Greece
facility: Novo Nordisk Investigational Site
city: Dublin 2
country: Ireland
facility: Novo Nordisk Investigational Site
city: Dublin
country: Ireland
facility: Novo Nordisk Investigational Site
city: Galway
country: Ireland
facility: Novo Nordisk Investigational Site
city: Petach Tikva
country: Israel
facility: Novo Nordisk Investigational Site
city: Rehovot
country: Israel
facility: Novo Nordisk Investigational Site
city: Milano
country: Italy
facility: Novo Nordisk Investigational Site
city: Milano
country: Italy
facility: Novo Nordisk Investigational Site
city: Padova
country: Italy
facility: Novo Nordisk Investigational Site
city: Roma
country: Italy
facility: Novo Nordisk Investigational Site
city: Sant'Andrea Delle Fratte (PG)
country: Italy
facility: Novo Nordisk Investigational Site
city: Torino
country: Italy
facility: Novo Nordisk Investigational Site
city: Ekaterinburg
country: Russian Federation
facility: Novo Nordisk Investigational Site
city: Kirov
country: Russian Federation
facility: Novo Nordisk Investigational Site
city: Moscow
country: Russian Federation
facility: Novo Nordisk Investigational Site
city: Saint-Petersburg
country: Russian Federation
facility: Novo Nordisk Investigational Site
city: Saratov
country: Russian Federation
facility: Novo Nordisk Investigational Site
city: Tomsk
country: Russian Federation
facility: Novo Nordisk Investigational Site
city: Ulianovsk
country: Russian Federation
facility: Novo Nordisk Investigational Site
city: Yoshkar-Ola
country: Russian Federation
facility: Novo Nordisk Investigational Site
city: Belgrade
country: Serbia
facility: Novo Nordisk Investigational Site
city: Barcelona
country: Spain
facility: Novo Nordisk Investigational Site
city: Bath
country: United Kingdom
facility: Novo Nordisk Investigational Site
city: Bradford
country: United Kingdom
facility: Novo Nordisk Investigational Site
city: Cambridge
country: United Kingdom
facility: Novo Nordisk Investigational Site
city: High Wycombe
country: United Kingdom
facility: Novo Nordisk Investigational Site
city: Leeds
country: United Kingdom
facility: Novo Nordisk Investigational Site
city: Middlesbrough
country: United Kingdom
facility: Novo Nordisk Investigational Site
city: Norwich
country: United Kingdom
facility: Novo Nordisk Investigational Site
city: Nottingham
country: United Kingdom
facility: Novo Nordisk Investigational Site
city: Oxford
country: United Kingdom
facility: Novo Nordisk Investigational Site
city: Truro
country: United Kingdom
facility: Novo Nordisk Investigational Site
Study officials:
References:
citation: Mathiesen ER, Alibegovic AC, Corcoy R, Dunne F, Feig DS, Hod M, Jia T, Kalyanam B, Kar S, Kautzky-Willer A, Marchesini C, Rea RD, Damm P; EXPECT study group. Insulin degludec versus insulin detemir, both in combination with insulin aspart, in the treatment of pregnant women with type 1 diabetes (EXPECT): an open-label, multinational, randomised, controlled, non-inferiority trial. Lancet Diabetes Endocrinol. 2023 Feb;11(2):86-95. doi: 10.1016/S2213-8587(22)00307-2. Epub 2023 Jan 6.