Detemir Versus NPH for Type 2 Diabetes Mellitus in Pregnancy (Determin)

Detemir Versus NPH for Type 2 Diabetes Mellitus in Pregnancy: a Comparative-effectiveness, Open Label, Randomized Controlled Trial

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).

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus, Type 2
• Intervention / Treatment: Drug: Neutral Protamine Hagedorn (NPH); Drug: Detemir insulin

• Study Type: Interventional
• Enrollment (Actual): 108
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • University of Texas Health Science Center of Houston

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / 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)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Neonates With Composite Adverse Neonatal Outcome	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	From the time of delivery to the time of discharge (about 2-14 days)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maternal Mean Fasting Glucose		perinatal to postpartum (32 weeks)
Maternal Mean Post Prandial Glucose		perinatal to postpartum (32 weeks)
Number of Maternal Subjects Who Experienced Hypoglycemic Events (<60 mg/dL) During Pregnancy		perinatal to postpartum (32 weeks)
Change in Maternal Weight During Pregnancy		perinatal to postpartum (32 weeks)
Number of Maternal Subjects Who Had Hypertensive Disorder During Pregnancy	Hypertensive disorder includes gestational hypertension, preeclampsia, or superimposed preeclampsia.	perinatal to postpartum (32 weeks)
Number of Maternal Subjects Who Had Preeclampsia With Severe Features		perinatal to postpartum (32 weeks)
Number of Subjects Who Had Cesarean Delivery		at delivery
Number of Subjects Who Had Operative Vaginal Delivery		at delivery
Gestational Weeks at Delivery		at delivery
Number of Neonates Who Where Small for Gestational Age (SGA)	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.	at delivery
Neonatal Hospital Admission Days		From the time of delivery to the time of discharge (about 2-14 days)
# of Neonates Who Had 5-minute Apgar Score < 7	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.	5 minutes after delivery
Number of Neonates Who Had Jaundice Requiring Therapy		From the time of delivery to the time of discharge (about 2-14 days)

Collaborators and Investigators

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

Publications and helpful links

General Publications

• Fishel Bartal M, Ward C, Blackwell SC, Ashby Cornthwaite JA, Zhang C, Refuerzo JS, Pedroza C, Lee KH, Chauhan SP, Sibai BM. Detemir vs neutral protamine Hagedorn insulin for diabetes mellitus in pregnancy: a comparative effectiveness, randomized controlled trial. Am J Obstet Gynecol. 2021 Jul;225(1):87.e1-87.e10. doi: 10.1016/j.ajog.2021.04.223. Epub 2021 Apr 15.

Study record dates

Study Major Dates

• Study Start (Actual): September 4, 2018
• Primary Completion (Actual): July 29, 2020
• Study Completion (Actual): July 29, 2020

Study Registration Dates

• First Submitted: August 2, 2018
• First Submitted That Met QC Criteria: August 2, 2018
• First Posted (Actual): August 8, 2018

Study Record Updates

• Last Update Posted (Actual): September 16, 2021
• Last Update Submitted That Met QC Criteria: August 20, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Keywords: Pregnancy
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Pregnancy Complications; Diabetes Mellitus; Diabetes Mellitus, Type 2; Pregnancy in Diabetics; Molecular Mechanisms of Pharmacological Action; Coagulants; Heparin Antagonists; Protamines
• Other Study ID Numbers: HSC-MS-18-0575

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• 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