Labor, Induced, Obesity, Oxytocin
Conditions
Keywords
Induction of labor, Pitocin, BMI
Brief summary
This is a randomized controlled trial in which women are allocated either 'high dose' or 'low dose' oxytocin infusions for induction of labour. The randomization is stratified by maternal body mass index.
Detailed description
Obesity is considered a major public health concerns and increases the risk of many comorbid medical conditions. Obesity in pregnancy places women at higher risk of obstetrical complications during pregnancy, delivery and postpartum. In particular, obese pregnant women have more difficulty going into labor, a longer labor course, and even with pharmacologic treatment, have a higher chance of requiring cesarean delivery. When pregnant women need help going into labor, they commonly receive a medication called Pitocin on the labor and delivery floor. Pitocin is the brand name and is a synthetic analog to the naturally produced oxytocin, a hormone secreted by mother when they naturally go into labor. This medication has been used widely around the world. There is emerging evidence that obese women need more oxytocin to go into labor compared to their lean cohorts. There are many studies to support the use of different oxytocin dosage protocols (both high and low dose infusion increments). Despite these evidences, a low dose oxytocin regimen is universally used in the United States, regardless of patient characteristics. This study is a double blinded randomized controlled trial. Both lean and obese cohorts will be recruited for the study. The investigators will randomly place both cohorts into the low or the high dose oxytocin regimen treatment group. The investigators, patients and providers will be blinded and will not know the specific assignments. The purpose of this study is to evaluate the effect of high dose oxytocin in the obese cohort. The hypothesis is that obese patient will have shorter time to delivery with the high dose oxytocin regimen without incurring any additional risks or adverse outcomes.
Interventions
DRUGOxytocin
Patients will be randomized to low dose or high dose oxytocin for induction of labor.
Sponsors
University of Arizona
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
This portion of the study will be carried out by the research pharmacy. Single (low dose) and triple (high dose) concentration of oxytocin will be premixed in the intravenous fluid bag in the pharmacy. Sequence generation for randomization will be created with 1:1 ratio in both the obese and lean group by the Department of Statistics. After the sequence is generated, ths list will be given to the research pharmacy. The premixed oxytocin medication will be sequentially labelled as OPS drug, patient #1, 2, 3 etc. per the allocation. Allocation concealment will also be carried out by pharmacy as these bags will completely appear identical after they are labelled numerically. Once a patient is randomized, the pharmacy will send up the appropriate concentration of oxytocin already premixed in the intravenous fluid bag, labelled as OPS drug, patient #. Lean group will be assigned at # 1-70 and obese group will be assigned at #71-140.
Intervention model description
4 Comparison groups: 1. Control group: Lean cohort: BMI ≤25, at \<20 weeks gestation or BMI ≤28 at a term gestation, low dose oxytocin protocol 2. Intervention group: Lean cohort: BMI ≤25, at \<20 weeks gestation or BMI ≤28 at a term gestation, high dose oxytocin protocol 3. Control group: Obese cohort: BMI ≥30, at \<20 weeks gestation or BMI ≥35 at a term gestation, low dose oxytocin protocol 4. Intervention group: Obese cohort: BMI ≥30, at \<20 weeks gestation or BMI ≥35 at a term gestation, high dose oxytocin protocol
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Singleton pregnancy ≥ 37 weeks gestation * Patient presented for induction of labor who is determined to be a candidate for oxytocin * Cephalic presentation * Reassuring fetal health assessment (no abnormal findings in fetal assessment, see below) * Meeting one of the following BMI category: Obese group: BMI ≥30 at \<20 weeks of pregnancy, or BMI ≥35 at a term gestation of pregnancy Lean group: BMI ≤25 at \<20 weeks of pregnancy, or BMI ≤28 at a term gestation of pregnancy
Exclusion criteria
* Non-reassuring fetal assessment at the time of recruitment * Previous cervical ripening agents (cytotec, cervidil, cervical Foley Balloon) * \<18 years of age * Prisoners * Any patients contraindicated for vaginal delivery * Multiple gestations * History of previous cesarean delivery * Patients with history of significant cardiac disease * Fetal demise * Estimated fetal weight greater than 4500 grams in diabetic and 5000 grams in non-diabetic mother * Ruptured membranes * Spontaneous labor (latent or active phase) * Augmentation of labor (latent or active phase)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Length of Time to Delivery | Start of induction to Delivery | Number of minutes from induction of labor with oxytocin infusion to delivery of infant, no maximum amount of time specified. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Terbutaline Use | Start of induction to Delivery | If terbutaline was injected during labor to decrease number or strength of contraction |
| Rate of Cesarean Delivery | Start of induction to Delivery | total number of patients who undergo cesarean delivery |
| Maximum Oxytocin Infusion Rate | Start of induction to Delivery | rate measured in milliunits/minute during induction of labour, no time limit applied. |
| Maternal Blood Loss | At delivery | Blood loss in milliliters |
| Number of Neonates With Apgar Score <7 | 5 minutes after birth | 5 minute Apgar Score \<7 \*Apgar is an acronym for which each criterion is given a minimum of 0 and maximum of 2 points: Appearance (skin color), Pulse (heart rate), Grimace (reflex irritability), Activity (muscle tone), Respiration |
| Rate of Cesarean Delivery for Labor Arrest | Start of induction to Delivery | Number of patients who undergo cesarean delivery due to labor arrest/ failed induction |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Lean-Control 1\) Control group: Lean cohort: BMI ≤25, at \<20 weeks gestation or BMI ≤28 at a term gestation, low dose oxytocin protocol
Low dose oxytocin regimen (the standard at Banner University Labor and Delivery, as well as across the United States): 30 units in 500cc 0.9% normal saline bag (60 milliunit/cc). Starting rate would be 2 milliunit/minute, or 2cc/hour. The medication will be increased by 2 milliunit/minute = 2cc/hr every 30 minutes until adequacy of contraction or cervical change. At 20 milliunit/minute = 20cc/hr, provider will assess patient for eligibility to continue to increase oxytocin dosage. | 35 |
| Lean-Intervention 2\) Intervention group: Lean cohort: BMI ≤25, at \<20 weeks gestation or BMI ≤28 at a term gestation, high dose oxytocin protocol
High dose oxytocin regimen (endorsed by American College of Obstetricians and Gynecologists): 90 units in 500cc 0.9% normal saline bag (180 milliunit/cc). Starting rate would be 6 milliunit/minute, or 2cc/hour. The medication will be increased by 6 milliunit/minute = 2cc/hr every 30 minutes until adequacy of contraction or cervical change. At 60 milliunit/minute = 20cc/hr, provider will assess patient for eligibility to continue to increase oxytocin dosage.
Oxytocin: Patients will be randomized to low dose or high dose oxytocin for induction of labor. | 35 |
| Obese-Control 3\) Control group: Obese cohort: BMI ≥30, at \<20 weeks gestation or BMI ≥35 at a term gestation, low dose oxytocin protocol
Low dose oxytocin regimen (the standard at Banner University Labor and Delivery, as well as across the United States): 30 units in 500cc 0.9% normal saline bag (60 milliunit/cc). Starting rate would be 2 milliunit/minute, or 2cc/hour. The medication will be increased by 2 milliunit/minute = 2cc/hr every 30 minutes until adequacy of contraction or cervical change. At 20 milliunit/minute = 20cc/hr, provider will assess patient for eligibility to continue to increase oxytocin dosage. | 35 |
| Obese-Intervention 4\) Intervention group: Obese cohort: BMI ≥30, at \<20 weeks gestation or BMI ≥35 at a term gestation, high dose oxytocin protocol
High dose oxytocin regimen (endorsed by American College of Obstetricians and Gynecologists): 90 units in 500cc 0.9% normal saline bag (180 milliunit/cc). Starting rate would be 6 milliunit/minute, or 2cc/hour. The medication will be increased by 6 milliunit/minute = 2cc/hr every 30 minutes until adequacy of contraction or cervical change. At 60 milliunit/minute = 20cc/hr, provider will assess patient for eligibility to continue to increase oxytocin dosage.
Oxytocin: Patients will be randomized to low dose or high dose oxytocin for induction of labor. | 35 |
| Total | 140 |
Baseline characteristics
| Characteristic | Lean-Intervention | Obese-Control | Obese-Intervention | Lean-Control | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 35 Participants | 35 Participants | 35 Participants | 35 Participants | 140 Participants |
| Age, Continuous | 28.54 years STANDARD_DEVIATION 5.2 | 30.63 years STANDARD_DEVIATION 5.31 | 26.80 years STANDARD_DEVIATION 4.51 | 28.89 years STANDARD_DEVIATION 5.76 | 28.71 years STANDARD_DEVIATION 5.33 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 4 Participants | 1 Participants | 0 Participants | 4 Participants | 9 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 2 Participants | 2 Participants | 1 Participants | 6 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) White | 28 Participants | 32 Participants | 33 Participants | 30 Participants | 123 Participants |
| Region of Enrollment United States | 35 participants | 35 participants | 35 participants | 35 participants | 140 participants |
| Sex: Female, Male Female | 35 Participants | 35 Participants | 35 Participants | 35 Participants | 140 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 35 | 0 / 35 | 0 / 35 | 0 / 35 |
| other Total, other adverse events | 0 / 35 | 0 / 35 | 0 / 35 | 0 / 35 |
| serious Total, serious adverse events | 0 / 35 | 0 / 35 | 0 / 35 | 0 / 35 |
Outcome results
Primary
Length of Time to Delivery
Number of minutes from induction of labor with oxytocin infusion to delivery of infant, no maximum amount of time specified.
Time frame: Start of induction to Delivery
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lean-Control | Length of Time to Delivery | 796 minutes | Standard Deviation 411 |
| Lean-Intervention | Length of Time to Delivery | 694 minutes | Standard Deviation 466 |
| Obese-Control | Length of Time to Delivery | 715 minutes | Standard Deviation 497 |
| Obese-Intervention | Length of Time to Delivery | 762 minutes | Standard Deviation 594 |
Secondary
Maternal Blood Loss
Blood loss in milliliters
Time frame: At delivery
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lean-Control | Maternal Blood Loss | 391.14 milliliters | Standard Deviation 207.96 |
| Lean-Intervention | Maternal Blood Loss | 358.57 milliliters | Standard Deviation 166.49 |
| Obese-Control | Maternal Blood Loss | 404.29 milliliters | Standard Deviation 226.99 |
| Obese-Intervention | Maternal Blood Loss | 491.43 milliliters | Standard Deviation 342.89 |
Secondary
Maximum Oxytocin Infusion Rate
rate measured in milliunits/minute during induction of labour, no time limit applied.
Time frame: Start of induction to Delivery
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lean-Control | Maximum Oxytocin Infusion Rate | 14.85 milliunits per minute | Standard Deviation 7.16 |
| Lean-Intervention | Maximum Oxytocin Infusion Rate | 33.00 milliunits per minute | Standard Deviation 25.64 |
| Obese-Control | Maximum Oxytocin Infusion Rate | 17.14 milliunits per minute | Standard Deviation 10.99 |
| Obese-Intervention | Maximum Oxytocin Infusion Rate | 39.60 milliunits per minute | Standard Deviation 21.09 |
Secondary
Number of Neonates With Apgar Score <7
5 minute Apgar Score \<7 \*Apgar is an acronym for which each criterion is given a minimum of 0 and maximum of 2 points: Appearance (skin color), Pulse (heart rate), Grimace (reflex irritability), Activity (muscle tone), Respiration
Time frame: 5 minutes after birth
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Lean-Control | Number of Neonates With Apgar Score <7 | 0 Participants |
| Lean-Intervention | Number of Neonates With Apgar Score <7 | 3 Participants |
| Obese-Control | Number of Neonates With Apgar Score <7 | 0 Participants |
| Obese-Intervention | Number of Neonates With Apgar Score <7 | 1 Participants |
Secondary
Number of Participants With Terbutaline Use
If terbutaline was injected during labor to decrease number or strength of contraction
Time frame: Start of induction to Delivery
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Lean-Control | Number of Participants With Terbutaline Use | 0 Participants |
| Lean-Intervention | Number of Participants With Terbutaline Use | 0 Participants |
| Obese-Control | Number of Participants With Terbutaline Use | 0 Participants |
| Obese-Intervention | Number of Participants With Terbutaline Use | 1 Participants |
Secondary
Rate of Cesarean Delivery
total number of patients who undergo cesarean delivery
Time frame: Start of induction to Delivery
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Lean-Control | Rate of Cesarean Delivery | 5 Participants |
| Lean-Intervention | Rate of Cesarean Delivery | 2 Participants |
| Obese-Control | Rate of Cesarean Delivery | 4 Participants |
| Obese-Intervention | Rate of Cesarean Delivery | 1 Participants |
Secondary
Rate of Cesarean Delivery for Labor Arrest
Number of patients who undergo cesarean delivery due to labor arrest/ failed induction
Time frame: Start of induction to Delivery
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Lean-Control | Rate of Cesarean Delivery for Labor Arrest | 1 Participants |
| Lean-Intervention | Rate of Cesarean Delivery for Labor Arrest | 1 Participants |
| Obese-Control | Rate of Cesarean Delivery for Labor Arrest | 3 Participants |
| Obese-Intervention | Rate of Cesarean Delivery for Labor Arrest | 0 Participants |