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)
• Enrollment: 108
• Location: 1
• Arms: 2
• Actual Duration (Months): 22.8
• Patients Per Site Per Month: 4.7

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 Disease	Intervention/Treatment	Phase
Diabetes Mellitus, Type 2	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

Arm	Intervention/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

	Site	City	State	Country	Postal Code
1	University of Texas Health Science Center of Houston	Houston	Texas	United States	77030

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)

• Study Protocol and Statistical Analysis Plan - Jul 31, 2018

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: Pregnancy
• Additional relevant MeSH terms: Pregnancy in Diabetics; Diabetes Mellitus; Diabetes Mellitus, Type 2; Protamines

Study Results

Participant Flow

Arm/Group Title	Detemir	Neutral Protamine Hagedorn (NPH)
Arm/Group Description	Detemir 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
STARTED	57	51
First Trimester Miscarriage	2	1
Major Fetal Anomalies (Hypoplastic Left Heart and Sacral Agenesis) With 2nd Trimester Stillbirth	1	0
Major Fetal Anomaly (Holoprosencephaly) With 2nd Trimester Pregnancy Termination	1	0
COMPLETED	53	50
NOT COMPLETED	4	1

Baseline Characteristics

Arm/Group Title	Detemir	Neutral Protamine Hagedorn (NPH)	Total
Arm/Group Description	Detemir 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	Total of all reporting groups
Overall Participants	57	51	108
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

Title	Number of Neonates With Composite Adverse Neonatal Outcome
Description	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
Time Frame	From 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 Title	Detemir	Neutral Protamine Hagedorn (NPH)
Arm/Group Description	Detemir 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 Participants	53	50
Count of Participants [Participants]	31 54.4%	35 68.6%

2. Secondary Outcome

Title	Maternal Mean Fasting Glucose
Time Frame	perinatal to postpartum (32 weeks)

Outcome Measure Data

Analysis Population Description

Data were not collected for this outcome measure.

Arm/Group Title	Detemir	Neutral Protamine Hagedorn (NPH)
Arm/Group Description	Detemir 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 Participants	0	0

3. Secondary Outcome

Title	Maternal Mean Post Prandial Glucose
Time Frame	perinatal to postpartum (32 weeks)

Outcome Measure Data

Analysis Population Description

Data were not collected for this outcome measure.

Arm/Group Title	Detemir	Neutral Protamine Hagedorn (NPH)
Arm/Group Description	Detemir 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 Participants	0	0

4. Secondary Outcome

Title	Number of Maternal Subjects Who Experienced Hypoglycemic Events (<60 mg/dL) During Pregnancy
Time Frame	perinatal to postpartum (32 weeks)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Detemir	Neutral Protamine Hagedorn (NPH)
Arm/Group Description	Detemir 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 Participants	53	50
Count of Participants [Participants]	8 14%	16 31.4%

5. Secondary Outcome

Title	Change in Maternal Weight During Pregnancy
Time Frame	perinatal to postpartum (32 weeks)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Detemir	Neutral Protamine Hagedorn (NPH)
Arm/Group Description	Detemir 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 Participants	53	50
Median (Inter-Quartile Range) [kilograms (kg)]	7.00	9.00

6. Secondary Outcome

Title	Number of Maternal Subjects Who Had Hypertensive Disorder During Pregnancy
Description	Hypertensive disorder includes gestational hypertension, preeclampsia, or superimposed preeclampsia.
Time Frame	perinatal to postpartum (32 weeks)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Detemir	Neutral Protamine Hagedorn (NPH)
Arm/Group Description	Detemir 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 Participants	53	50
Count of Participants [Participants]	22 38.6%	27 52.9%

7. Secondary Outcome

Title	Number of Maternal Subjects Who Had Preeclampsia With Severe Features
Time Frame	perinatal to postpartum (32 weeks)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Detemir	Neutral Protamine Hagedorn (NPH)
Arm/Group Description	Detemir 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 Participants	53	50
Count of Participants [Participants]	12 21.1%	16 31.4%

8. Secondary Outcome

Title	Number of Subjects Who Had Cesarean Delivery
Time Frame	at delivery

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Detemir	Neutral Protamine Hagedorn (NPH)
Arm/Group Description	Detemir 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 Participants	53	50
Count of Participants [Participants]	32 56.1%	30 58.8%

9. Secondary Outcome

Title	Number of Subjects Who Had Operative Vaginal Delivery
Time Frame	at delivery

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Detemir	Neutral Protamine Hagedorn (NPH)
Arm/Group Description	Detemir 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 Participants	53	50
Count of Participants [Participants]	1 1.8%	0 0%

10. Secondary Outcome

Title	Gestational Weeks at Delivery
Time Frame	at delivery

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Detemir	Neutral Protamine Hagedorn (NPH)
Arm/Group Description	Detemir 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 Participants	53	50
Median (Inter-Quartile Range) [weeks]	37.10	37.00

11. Secondary Outcome

Title	Number of Neonates Who Where Small for Gestational Age (SGA)
Description	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.
Time Frame	at delivery

Outcome Measure Data

Analysis Population Description

All participants had singleton pregnancies (that is, there were no twins).

Arm/Group Title	Detemir	Neutral Protamine Hagedorn (NPH)
Arm/Group Description	Detemir 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 Participants	53	50
Count of Participants [Participants]	4 7%	6 11.8%

12. Secondary Outcome

Title	Neonatal Hospital Admission Days
Time Frame	From 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 Title	Detemir	Neutral Protamine Hagedorn (NPH)
Arm/Group Description	Detemir 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 Participants	53	50
Median (Inter-Quartile Range) [days]	4.0	4.1

13. Secondary Outcome

Title	# of Neonates Who Had 5-minute Apgar Score < 7
Description	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.
Time Frame	5 minutes after delivery

Outcome Measure Data

Analysis Population Description

All participants had singleton pregnancies (that is, there were no twins).

Arm/Group Title	Detemir	Neutral Protamine Hagedorn (NPH)
Arm/Group Description	Detemir 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 Participants	53	50
Count of Participants [Participants]	3 5.3%	2 3.9%

14. Secondary Outcome

Title	Number of Neonates Who Had Jaundice Requiring Therapy
Time Frame	From 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 Title	Detemir	Neutral Protamine Hagedorn (NPH)
Arm/Group Description	Detemir 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 Participants	53	50
Count of Participants [Participants]	15 26.3%	11 21.6%

Adverse Events

Time Frame	perinatal to postpartum (32 weeks)
Adverse Event Reporting Description	All deaths were pregnancy losses, and there were no maternal deaths.
Arm/Group Title	Detemir		Neutral Protamine Hagedorn (NPH)
Arm/Group Description	Detemir 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
	Detemir		Neutral Protamine Hagedorn (NPH)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/57 (7%)		1/51 (2%)
Serious Adverse Events
	Detemir		Neutral Protamine Hagedorn (NPH)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	16/57 (28.1%)		10/51 (19.6%)
Pregnancy, puerperium and perinatal conditions
First trimester miscarriage	2/57 (3.5%)	2	1/51 (2%)	1
Major fetal anomaly (holoprosencephaly) with termination of pregnancy in 2nd trimester	1/57 (1.8%)		0/51 (0%)
Major fetal anomalies (hypoplastic left heart and sacral agenesis) with stillbirth in 2nd trimester	1/57 (1.8%)		0/51 (0%)
Maternal admission to the hospital during pregnancy, other than admission for labor	7/57 (12.3%)	7	8/51 (15.7%)	8
Maternal readmission to hospital after delivery	5/57 (8.8%)	5	1/51 (2%)	1
Other (Not Including Serious) Adverse Events
	Detemir		Neutral Protamine Hagedorn (NPH)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/53 (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.