Determin: Detemir Versus NPH for Type 2 Diabetes Mellitus in Pregnancy

Sponsor
The University of Texas Health Science Center, Houston (Other)
Overall Status
Completed
CT.gov ID
NCT03620890
Collaborator
(none)
108
Enrollment
1
Location
2
Arms
22.8
Actual Duration (Months)
4.7
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

To determine whether use of detemir compared to neutral protamine hagedorn (NPH) decreases rates of composite neonatal outcome and maternal hypoglycemia events in women with Type 2 Diabetes Mellitus (T2DM).

Condition or DiseaseIntervention/TreatmentPhase
  • Drug: Neutral Protamine Hagedorn (NPH)
  • Drug: Detemir insulin
Phase 4

Study Design

Study Type:
Interventional
Actual Enrollment :
108 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Detemir Versus NPH for Type 2 Diabetes Mellitus in Pregnancy: a Comparative-effectiveness, Open Label, Randomized Controlled Trial
Actual Study Start Date :
Sep 4, 2018
Actual Primary Completion Date :
Jul 29, 2020
Actual Study Completion Date :
Jul 29, 2020

Arms and Interventions

ArmIntervention/Treatment
Active Comparator: Neutral Protamine Hagedorn (NPH)

NPH will peak between 4-12 hours after injection with a duration of action around 14 hours

Drug: Neutral Protamine Hagedorn (NPH)
NPH will peak between 4-12 hours after injection with a duration of action around 14 hours

Active Comparator: Detemir

Detemir is characterized by a gentle rise and fall with a longer duration of action (18-20 hours)

Drug: Detemir insulin
Detemir is characterized by a gentle rise and fall with a longer duration of action (18-20 hours)

Outcome Measures

Primary Outcome Measures

  1. Number of Neonates With Composite Adverse Neonatal Outcome [From the time of delivery to the time of discharge (about 2-14 days)]

    Composite Adverse Neonatal Outcome includes 1 or more of any of the following: Neonatal intensive care unit (NICU) admission or Neonatal hypoglycemia (<40 mg/dL in the first 24 hours of life and less than 50 mg/dL after) or requiring medical therapy or Respiratory distress (need for at least 4 hours of respiratory support with supplemental oxygen, continuous positive airway pressure or ventilation at the first 24 hours of life or Shoulder dystocia - defined as the need for any extra maneuvers, other than gentle downward traction of the fetal head in order to deliver the fetal body after the fetal head has been delivered or Large for gestational age (LGA) -weight over 90th percentile of the expected value according to gestational age or Macrosomia- Fetal weight above 4000g

Secondary Outcome Measures

  1. Maternal Mean Fasting Glucose [perinatal to postpartum (32 weeks)]

  2. Maternal Mean Post Prandial Glucose [perinatal to postpartum (32 weeks)]

  3. Number of Maternal Subjects Who Experienced Hypoglycemic Events (<60 mg/dL) During Pregnancy [perinatal to postpartum (32 weeks)]

  4. Change in Maternal Weight During Pregnancy [perinatal to postpartum (32 weeks)]

  5. Number of Maternal Subjects Who Had Hypertensive Disorder During Pregnancy [perinatal to postpartum (32 weeks)]

    Hypertensive disorder includes gestational hypertension, preeclampsia, or superimposed preeclampsia.

  6. Number of Maternal Subjects Who Had Preeclampsia With Severe Features [perinatal to postpartum (32 weeks)]

  7. Number of Subjects Who Had Cesarean Delivery [at delivery]

  8. Number of Subjects Who Had Operative Vaginal Delivery [at delivery]

  9. Gestational Weeks at Delivery [at delivery]

  10. Number of Neonates Who Where Small for Gestational Age (SGA) [at delivery]

    Small for gestational age (SGA) means that a fetus or an infant is smaller or less developed than normal for the baby's sex and gestational age. Small for gestational age (SGA) is defined as a birth weight that is below the 10th percentile.

  11. Neonatal Hospital Admission Days [From the time of delivery to the time of discharge (about 2-14 days)]

  12. # of Neonates Who Had 5-minute Apgar Score < 7 [5 minutes after delivery]

    The Apgar score is determined by evaluating the newborn baby on each of five criteria (appearance, pulse, grimace, activity, respiration) on a scale from zero to two, then summing the five values obtained. The total score ranges from zero to 10. A higher score indicates a better outcome.

  13. Number of Neonates Who Had Jaundice Requiring Therapy [From the time of delivery to the time of discharge (about 2-14 days)]

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
Female
Accepts Healthy Volunteers:
No
Inclusion Criteria:
  • Preexisting type 2 diabetes mellitus requiring medical treatment or

  • overt diabetes diagnosed prior to 20 weeks of gestation using either Hemoglobin A1c (HBA1C) ≥ 6.5 or fasting glucose ≥126 mg/dl or random blood glucose ≥ 200 mg/dl or two step method ( 50g glucose challenge test (GCT) >135 mg/dl followed by 100 GCT with at least 2 values above thresholds: Fasting Blood Glucose (FBG) >90, 1 hr >180, 2 hr > 155, 3 hr > 140 mg/dl).

  • Gestational age ≤20 weeks

  • Willing to start insulin therapy or to continue insulin treatment during pregnancy

  • Singleton or twin pregnancy

Exclusion Criteria:
  • Known allergy/prior adverse reaction to NPH/detemir

  • Patients <18y

  • Known major fetal anomalies

  • Diabetic nephropathy (Creatinine (Cr)≥1.5)

  • Diabetic proliferative retinopathy

  • Patients with Type 1 diabetes or gestational diabetes

Contacts and Locations

Locations

SiteCityStateCountryPostal Code
1University of Texas Health Science Center of HoustonHoustonTexasUnited States77030

Sponsors and Collaborators

  • The University of Texas Health Science Center, Houston

Investigators

  • Principal Investigator: Michal Fishel Bartal, MD, University of Texas Health Science Center of Houston

Study Documents (Full-Text)

More Information

Publications

None provided.
Responsible Party:
Michal Fishel Bartal, Assistant Professor of OB GYN, The University of Texas Health Science Center, Houston
ClinicalTrials.gov Identifier:
NCT03620890
Other Study ID Numbers:
  • HSC-MS-18-0575
First Posted:
Aug 8, 2018
Last Update Posted:
Sep 16, 2021
Last Verified:
Aug 1, 2021
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Product Manufactured in and Exported from the U.S.:
No
Keywords provided by Michal Fishel Bartal, Assistant Professor of OB GYN, The University of Texas Health Science Center, Houston
Additional relevant MeSH terms:

Study Results

Participant Flow

Recruitment Details
Pre-assignment Detail
Arm/Group TitleDetemirNeutral Protamine Hagedorn (NPH)
Arm/Group DescriptionDetemir insulin: Detemir is characterized by a gentle rise and fall with a longer duration of action (18-20 hours)Neutral Protamine Hagedorn (NPH): NPH will peak between 4-12 hours after injection with a duration of action around 14 hours
Period Title: Overall Study
STARTED5751
First Trimester Miscarriage21
Major Fetal Anomalies (Hypoplastic Left Heart and Sacral Agenesis) With 2nd Trimester Stillbirth10
Major Fetal Anomaly (Holoprosencephaly) With 2nd Trimester Pregnancy Termination10
COMPLETED5350
NOT COMPLETED41

Baseline Characteristics

Arm/Group TitleDetemirNeutral Protamine Hagedorn (NPH)Total
Arm/Group DescriptionDetemir insulin: Detemir is characterized by a gentle rise and fall with a longer duration of action (18-20 hours)Neutral Protamine Hagedorn (NPH): NPH will peak between 4-12 hours after injection with a duration of action around 14 hoursTotal of all reporting groups
Overall Participants5751108
Age (Count of Participants)
<=18 years
0
0%
0
0%
0
0%
Between 18 and 65 years
57
100%
51
100%
108
100%
>=65 years
0
0%
0
0%
0
0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]
32.1
(6.2)
32.5
(6.0)
32.3
(6.1)
Sex: Female, Male (Count of Participants)
Female
57
100%
51
100%
108
100%
Male
0
0%
0
0%
0
0%
Race/Ethnicity, Customized (Count of Participants)
Asian
4
7%
0
0%
4
3.7%
Hispanic
36
63.2%
31
60.8%
67
62%
Non-Hispanic Black
14
24.6%
14
27.5%
28
25.9%
Non-Hispanic White
3
5.3%
6
11.8%
9
8.3%
Region of Enrollment (Count of Participants)
United States
57
100%
51
100%
108
100%
Number of maternal participants who had private insurance for prenatal care (Count of Participants)
Count of Participants [Participants]
22
38.6%
18
35.3%
40
37%
Number of maternal participants who were nulliparous (Count of Participants)
Count of Participants [Participants]
5
8.8%
7
13.7%
12
11.1%
Number of maternal participants with body mass index (BMI) greater than 30 (Count of Participants)
Count of Participants [Participants]
51
89.5%
38
74.5%
89
82.4%
Number of maternal participants with diabetes mellitus diagnosed before pregnancy (Count of Participants)
Count of Participants [Participants]
44
77.2%
42
82.4%
86
79.6%
Number of maternal participants with HbA1c level greater than 6.5% (Count of Participants)
Count of Participants [Participants]
37
64.9%
34
66.7%
71
65.7%
Number of maternal participants with chronic hypertension (Count of Participants)
Count of Participants [Participants]
12
21.1%
17
33.3%
29
26.9%
Number of maternal participants with depression or anxiety (Count of Participants)
Count of Participants [Participants]
7
12.3%
9
17.6%
16
14.8%
Number of maternal participants with thyroid disease (Count of Participants)
Count of Participants [Participants]
2
3.5%
4
7.8%
6
5.6%
Number of maternal participants who smoked during pregnancy (Count of Participants)
Count of Participants [Participants]
2
3.5%
0
0%
2
1.9%
Number of maternal participants who used alcohol during pregnancy (Count of Participants)
Count of Participants [Participants]
2
3.5%
0
0%
2
1.9%
Number of maternal participants who used substances during pregnancy (Count of Participants)
Count of Participants [Participants]
3
5.3%
1
2%
4
3.7%
Number of maternal participants who used rapid- or short-acting insulin (Count of Participants)
Count of Participants [Participants]
38
66.7%
41
80.4%
79
73.1%
Number of maternal participants who used aspirin during pregnancy (Count of Participants)
Count of Participants [Participants]
27
47.4%
29
56.9%
56
51.9%

Outcome Measures

1. Primary Outcome
TitleNumber of Neonates With Composite Adverse Neonatal Outcome
DescriptionComposite Adverse Neonatal Outcome includes 1 or more of any of the following: Neonatal intensive care unit (NICU) admission or Neonatal hypoglycemia (<40 mg/dL in the first 24 hours of life and less than 50 mg/dL after) or requiring medical therapy or Respiratory distress (need for at least 4 hours of respiratory support with supplemental oxygen, continuous positive airway pressure or ventilation at the first 24 hours of life or Shoulder dystocia - defined as the need for any extra maneuvers, other than gentle downward traction of the fetal head in order to deliver the fetal body after the fetal head has been delivered or Large for gestational age (LGA) -weight over 90th percentile of the expected value according to gestational age or Macrosomia- Fetal weight above 4000g
Time FrameFrom the time of delivery to the time of discharge (about 2-14 days)

Outcome Measure Data

Analysis Population Description
All participants had singleton pregnancies (that is, there were no twins).
Arm/Group TitleDetemirNeutral Protamine Hagedorn (NPH)
Arm/Group DescriptionDetemir insulin: Detemir is characterized by a gentle rise and fall with a longer duration of action (18-20 hours)Neutral Protamine Hagedorn (NPH): NPH will peak between 4-12 hours after injection with a duration of action around 14 hours
Measure Participants5350
Count of Participants [Participants]
31
54.4%
35
68.6%
2. Secondary Outcome
TitleMaternal Mean Fasting Glucose
Description
Time Frameperinatal to postpartum (32 weeks)

Outcome Measure Data

Analysis Population Description
Data were not collected for this outcome measure.
Arm/Group TitleDetemirNeutral Protamine Hagedorn (NPH)
Arm/Group DescriptionDetemir insulin: Detemir is characterized by a gentle rise and fall with a longer duration of action (18-20 hours)Neutral Protamine Hagedorn (NPH): NPH will peak between 4-12 hours after injection with a duration of action around 14 hours
Measure Participants00
3. Secondary Outcome
TitleMaternal Mean Post Prandial Glucose
Description
Time Frameperinatal to postpartum (32 weeks)

Outcome Measure Data

Analysis Population Description
Data were not collected for this outcome measure.
Arm/Group TitleDetemirNeutral Protamine Hagedorn (NPH)
Arm/Group DescriptionDetemir insulin: Detemir is characterized by a gentle rise and fall with a longer duration of action (18-20 hours)Neutral Protamine Hagedorn (NPH): NPH will peak between 4-12 hours after injection with a duration of action around 14 hours
Measure Participants00
4. Secondary Outcome
TitleNumber of Maternal Subjects Who Experienced Hypoglycemic Events (<60 mg/dL) During Pregnancy
Description
Time Frameperinatal to postpartum (32 weeks)

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group TitleDetemirNeutral Protamine Hagedorn (NPH)
Arm/Group DescriptionDetemir insulin: Detemir is characterized by a gentle rise and fall with a longer duration of action (18-20 hours)Neutral Protamine Hagedorn (NPH): NPH will peak between 4-12 hours after injection with a duration of action around 14 hours
Measure Participants5350
Count of Participants [Participants]
8
14%
16
31.4%
5. Secondary Outcome
TitleChange in Maternal Weight During Pregnancy
Description
Time Frameperinatal to postpartum (32 weeks)

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group TitleDetemirNeutral Protamine Hagedorn (NPH)
Arm/Group DescriptionDetemir insulin: Detemir is characterized by a gentle rise and fall with a longer duration of action (18-20 hours)Neutral Protamine Hagedorn (NPH): NPH will peak between 4-12 hours after injection with a duration of action around 14 hours
Measure Participants5350
Median (Inter-Quartile Range) [kilograms (kg)]
7.00
9.00
6. Secondary Outcome
TitleNumber of Maternal Subjects Who Had Hypertensive Disorder During Pregnancy
DescriptionHypertensive disorder includes gestational hypertension, preeclampsia, or superimposed preeclampsia.
Time Frameperinatal to postpartum (32 weeks)

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group TitleDetemirNeutral Protamine Hagedorn (NPH)
Arm/Group DescriptionDetemir insulin: Detemir is characterized by a gentle rise and fall with a longer duration of action (18-20 hours)Neutral Protamine Hagedorn (NPH): NPH will peak between 4-12 hours after injection with a duration of action around 14 hours
Measure Participants5350
Count of Participants [Participants]
22
38.6%
27
52.9%
7. Secondary Outcome
TitleNumber of Maternal Subjects Who Had Preeclampsia With Severe Features
Description
Time Frameperinatal to postpartum (32 weeks)

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group TitleDetemirNeutral Protamine Hagedorn (NPH)
Arm/Group DescriptionDetemir insulin: Detemir is characterized by a gentle rise and fall with a longer duration of action (18-20 hours)Neutral Protamine Hagedorn (NPH): NPH will peak between 4-12 hours after injection with a duration of action around 14 hours
Measure Participants5350
Count of Participants [Participants]
12
21.1%
16
31.4%
8. Secondary Outcome
TitleNumber of Subjects Who Had Cesarean Delivery
Description
Time Frameat delivery

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group TitleDetemirNeutral Protamine Hagedorn (NPH)
Arm/Group DescriptionDetemir insulin: Detemir is characterized by a gentle rise and fall with a longer duration of action (18-20 hours)Neutral Protamine Hagedorn (NPH): NPH will peak between 4-12 hours after injection with a duration of action around 14 hours
Measure Participants5350
Count of Participants [Participants]
32
56.1%
30
58.8%
9. Secondary Outcome
TitleNumber of Subjects Who Had Operative Vaginal Delivery
Description
Time Frameat delivery

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group TitleDetemirNeutral Protamine Hagedorn (NPH)
Arm/Group DescriptionDetemir insulin: Detemir is characterized by a gentle rise and fall with a longer duration of action (18-20 hours)Neutral Protamine Hagedorn (NPH): NPH will peak between 4-12 hours after injection with a duration of action around 14 hours
Measure Participants5350
Count of Participants [Participants]
1
1.8%
0
0%
10. Secondary Outcome
TitleGestational Weeks at Delivery
Description
Time Frameat delivery

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group TitleDetemirNeutral Protamine Hagedorn (NPH)
Arm/Group DescriptionDetemir insulin: Detemir is characterized by a gentle rise and fall with a longer duration of action (18-20 hours)Neutral Protamine Hagedorn (NPH): NPH will peak between 4-12 hours after injection with a duration of action around 14 hours
Measure Participants5350
Median (Inter-Quartile Range) [weeks]
37.10
37.00
11. Secondary Outcome
TitleNumber of Neonates Who Where Small for Gestational Age (SGA)
DescriptionSmall for gestational age (SGA) means that a fetus or an infant is smaller or less developed than normal for the baby's sex and gestational age. Small for gestational age (SGA) is defined as a birth weight that is below the 10th percentile.
Time Frameat delivery

Outcome Measure Data

Analysis Population Description
All participants had singleton pregnancies (that is, there were no twins).
Arm/Group TitleDetemirNeutral Protamine Hagedorn (NPH)
Arm/Group DescriptionDetemir insulin: Detemir is characterized by a gentle rise and fall with a longer duration of action (18-20 hours)Neutral Protamine Hagedorn (NPH): NPH will peak between 4-12 hours after injection with a duration of action around 14 hours
Measure Participants5350
Count of Participants [Participants]
4
7%
6
11.8%
12. Secondary Outcome
TitleNeonatal Hospital Admission Days
Description
Time FrameFrom the time of delivery to the time of discharge (about 2-14 days)

Outcome Measure Data

Analysis Population Description
All participants had singleton pregnancies (that is, there were no twins).
Arm/Group TitleDetemirNeutral Protamine Hagedorn (NPH)
Arm/Group DescriptionDetemir insulin: Detemir is characterized by a gentle rise and fall with a longer duration of action (18-20 hours)Neutral Protamine Hagedorn (NPH): NPH will peak between 4-12 hours after injection with a duration of action around 14 hours
Measure Participants5350
Median (Inter-Quartile Range) [days]
4.0
4.1
13. Secondary Outcome
Title# of Neonates Who Had 5-minute Apgar Score < 7
DescriptionThe Apgar score is determined by evaluating the newborn baby on each of five criteria (appearance, pulse, grimace, activity, respiration) on a scale from zero to two, then summing the five values obtained. The total score ranges from zero to 10. A higher score indicates a better outcome.
Time Frame5 minutes after delivery

Outcome Measure Data

Analysis Population Description
All participants had singleton pregnancies (that is, there were no twins).
Arm/Group TitleDetemirNeutral Protamine Hagedorn (NPH)
Arm/Group DescriptionDetemir insulin: Detemir is characterized by a gentle rise and fall with a longer duration of action (18-20 hours)Neutral Protamine Hagedorn (NPH): NPH will peak between 4-12 hours after injection with a duration of action around 14 hours
Measure Participants5350
Count of Participants [Participants]
3
5.3%
2
3.9%
14. Secondary Outcome
TitleNumber of Neonates Who Had Jaundice Requiring Therapy
Description
Time FrameFrom the time of delivery to the time of discharge (about 2-14 days)

Outcome Measure Data

Analysis Population Description
All participants had singleton pregnancies (that is, there were no twins).
Arm/Group TitleDetemirNeutral Protamine Hagedorn (NPH)
Arm/Group DescriptionDetemir insulin: Detemir is characterized by a gentle rise and fall with a longer duration of action (18-20 hours)Neutral Protamine Hagedorn (NPH): NPH will peak between 4-12 hours after injection with a duration of action around 14 hours
Measure Participants5350
Count of Participants [Participants]
15
26.3%
11
21.6%

Adverse Events

Time Frameperinatal to postpartum (32 weeks)
Adverse Event Reporting Description All deaths were pregnancy losses, and there were no maternal deaths.
Arm/Group TitleDetemirNeutral Protamine Hagedorn (NPH)
Arm/Group DescriptionDetemir insulin: Detemir is characterized by a gentle rise and fall with a longer duration of action (18-20 hours)Neutral Protamine Hagedorn (NPH): NPH will peak between 4-12 hours after injection with a duration of action around 14 hours
All Cause Mortality
DetemirNeutral Protamine Hagedorn (NPH)
Affected / at Risk (%)# EventsAffected / at Risk (%)# Events
Total4/57 (7%) 1/51 (2%)
Serious Adverse Events
DetemirNeutral Protamine Hagedorn (NPH)
Affected / at Risk (%)# EventsAffected / at Risk (%)# Events
Total16/57 (28.1%) 10/51 (19.6%)
Pregnancy, puerperium and perinatal conditions
First trimester miscarriage2/57 (3.5%) 21/51 (2%) 1
Major fetal anomaly (holoprosencephaly) with termination of pregnancy in 2nd trimester1/57 (1.8%) 0/51 (0%)
Major fetal anomalies (hypoplastic left heart and sacral agenesis) with stillbirth in 2nd trimester1/57 (1.8%) 0/51 (0%)
Maternal admission to the hospital during pregnancy, other than admission for labor7/57 (12.3%) 78/51 (15.7%) 8
Maternal readmission to hospital after delivery5/57 (8.8%) 51/51 (2%) 1
Other (Not Including Serious) Adverse Events
DetemirNeutral Protamine Hagedorn (NPH)
Affected / at Risk (%)# EventsAffected / at Risk (%)# Events
Total0/53 (0%) 0/50 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

Name/TitleMichal Fishel Bartal, MD, Assistant Professor
OrganizationThe University of Texas Health Science Center at Houston
Phone713-500-6421
EmailMichal.F.Bartal@uth.tmc.edu
Responsible Party:
Michal Fishel Bartal, Assistant Professor of OB GYN, The University of Texas Health Science Center, Houston
ClinicalTrials.gov Identifier:
NCT03620890
Other Study ID Numbers:
  • HSC-MS-18-0575
First Posted:
Aug 8, 2018
Last Update Posted:
Sep 16, 2021
Last Verified:
Aug 1, 2021