Chronic Hypertension in Pregnancy
Conditions
Keywords
Amlodipine besylate, Breast milk, Pharmacokinetics, Chronic hypertension, Pregnancy
Brief summary
This is a phase IV prospective trial to collect and analyze information about the maternal pharmacokinetics of amlodipine besylate at the time of delivery and during postpartum lactation. The study will also evaluate amlodipine concentrations in the infants of breastfeeding mothers who are taking amlodipine besylate for treatment chronic hypertension.
Detailed description
We plan to evaluate the pharmacokinetics of amlodipine besylate at the time of delivery, to determine if transplacental passage of the drug occurs. We will also examine the drug kinetics in postpartum lactation to establish whether amlodipine is excreted into breast milk. The outcomes of interest are plasma concentration of amlodipine at delivery and the drug concentrations in blood and breast milk over a twenty-hour steady-state period following milk-supply establishment. Fifteen patients already taking 5 mg of amlodipine during pregnancy for the treatment of chronic hypertension will be recruited from the antepartum Obstetric Complications Clinic at Parkland Hospital. Only women who are breastfeeding will be eligible for the study. Patients who elect to participate in the study will continue their amlodipine 5 mg dosing through delivery and into the postpartum period. Maternal blood will be drawn within one hour of delivery and fetal cord blood collected at the time of delivery. Patients will then have blood drawn over a 24 hour period beginning on postpartum day 2 after delivery following administration of their once-daily amlodipine dose. At each blood draw, the patient will also use a breast pump to express breast milk for paired analysis. Both blood and breast milk amlodipine levels will be calculated for all samples. The levels will be used to determine the pharmacokinetics of amlodipine in the peri- and postpartum patient, including concentrations in plasma and breast milk. In addition to collecting maternal data, a range of clinical information will be collected on each study patient's infant including weight, Apgar scores, hemodynamic parameters, physical examination and hospital course. This information will be used to screen for any potential complications associated with infant exposure to amlodipine. An infant blood sample will also be obtained in conjunction with the routine neonatal blood collection that occurs at 1-2 days of postnatal life and this will be analyzed to determine serum amlodipine concentration in breastfeeding infants.
Interventions
Pregnant and postpartum women will continue taking amlodipine besylate 5 mg for treatment of chronic hypertension as prescribed by their clinician.
Sponsors
National Center for Advancing Translational Sciences (NCATS)
University of Texas Southwestern Medical Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 50 Years
Healthy volunteers
No
Inclusion criteria
* 18 years or older; * Pregnant female * Already taking amlodipine 5 mg for treatment of chronic hypertension in pregnancy; * Hospitalized following routine term vaginal delivery or uncomplicated cesarean delivery * Breastfeeding or breast and bottle-feeding their infant
Exclusion criteria
* Known kidney disease * Delivery complicated by chorioamnionitis, endometritis or postpartum hemorrhage * Administration of greater than 5 mg of amlodipine in 24 hour period
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Drug Level/Concentration in Infant Blood (Amlodipine Level/Concentration) | Infant blood sample drawn at approximately 36 hours of life | Infant amlodipine level/concentration will be determined. |
| Maximal Amlodipine Maternal Serum Concentration | Maternal blood samples were obtained at 4, 6, 8, 12, 15 and 24 hours after amlodipine dosing | The maximum concentration of amlodipine detected in the maternal serum in the peripartum period was measured. |
| Half-life of Amlodipine in Maternal Plasma | Maternal blood samples were obtained at 4, 6, 8, 12, 15 and 24 hours after amlodipine dosing | The half-life of amlodipine in the maternal plasma in the peripartum period was measured. |
| Drug Levels/Concentration in Cord Blood (Amlodipine Levels/Concentrations) | Pair maternal blood sample and cord blood sample will draw within 1 hour of delivery | Maternal and cord blood amlodipine levels/concentrations will be determined. |
| Amlodipine Concentration in Breastmilk | Breast milk samples were obtained at 4, 6, 8, 12, 15 and 24 hours after amlodipine dosing | The concentration of amlodipine besylate was measured in breastmilk samples. |
| Clearance Rate of Plasma Amlodipine | Maternal blood samples were obtained at 4, 6, 8, 12, 15 and 24 hours after amlodipine dosing | The clearance rate of amlodipine from the maternal plasma was measured. |
| Area Under the Curve for Amlodipine in the Maternal Serum | Maternal blood samples will be obtained at 4, 6, 8, 12, 15 and 24 hours after amlodipine dosing | The time to peak amlodipine concentration in the maternal serum in the peripartum period was be measured. |
| Time to Maximal Concentration in the Maternal Serum. | Maternal blood samples were obtained at 4, 6, 8, 12, 15 and 24 hours after amlodipine dosing | The time to reach maximal amlodipine concentration in the maternal serum in the peripartum period was measured. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Infant Gestational Age at Delivery. | Gestational age at the time of birth | The mean gestational age of infants born to mothers taking Amlodipine besylate 5 mg daily was collected. |
| Infant Length of Stay. | Time from birth to hospital discharge | The length of stay of infants born to women taking amlodipine besylate will be collected. |
| Major Infant Complications | During neonatal hospitalization | Any major complications experienced by infants born to women taking amlodipine besylate including NICU admission, intraventricular hemorrhage, neonatal seizures, need for respiratory support and apnea were collected. |
| Neonatal Birth Weight | Neonatal weight at the time of birth. | The neonatal weight at birth was collected. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Pregnant Women Taking Amlodipine Women already taking amlodipine besylate 5 mg for treatment of chronic hypertension in pregnancy who plan to breastfeed postpartum will be assigned to the single experimental arm.
Amlodipine besylate: Pregnant and postpartum women will continue taking amlodipine besylate 5 mg for treatment of chronic hypertension as prescribed by their clinician. | 16 |
| Total | 16 |
Baseline characteristics
| Characteristic | Pregnant Women Taking Amlodipine |
|---|---|
| Age, Continuous | 33.2 years STANDARD_DEVIATION 5.8 |
| Race/Ethnicity, Customized Black or African American | 3 Participants |
| Race/Ethnicity, Customized Hispanic | 12 Participants |
| Race/Ethnicity, Customized Other | 1 Participants |
| Sex: Female, Male Female | 16 Participants |
| Sex: Female, Male Male | NA Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 16 |
| serious Total, serious adverse events | 0 / 16 |
Outcome results
Primary
Amlodipine Concentration in Breastmilk
The concentration of amlodipine besylate was measured in breastmilk samples.
Time frame: Breast milk samples were obtained at 4, 6, 8, 12, 15 and 24 hours after amlodipine dosing
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Pregnant Women Taking Amlodipine | Amlodipine Concentration in Breastmilk | NA ng/mL |
Primary
Area Under the Curve for Amlodipine in the Maternal Serum
The time to peak amlodipine concentration in the maternal serum in the peripartum period was be measured.
Time frame: Maternal blood samples will be obtained at 4, 6, 8, 12, 15 and 24 hours after amlodipine dosing
Population: Although 16 women were enrolled in the study, only 11 of the 16 had blood drawn at the time of delivery. This was due to limitations of study personnel availability to attend the deliveries of all study patients
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pregnant Women Taking Amlodipine | Area Under the Curve for Amlodipine in the Maternal Serum | 53.4 (hr*ng)/mL | Standard Deviation 19.8 |
Primary
Clearance Rate of Plasma Amlodipine
The clearance rate of amlodipine from the maternal plasma was measured.
Time frame: Maternal blood samples were obtained at 4, 6, 8, 12, 15 and 24 hours after amlodipine dosing
Population: Although 16 women were enrolled in the trial, only 11 had their blood drawn at the time of delivery due to limited availability of study personnel.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pregnant Women Taking Amlodipine | Clearance Rate of Plasma Amlodipine | 109.7 L/hr | Standard Deviation 58.9 |
Primary
Drug Level/Concentration in Infant Blood (Amlodipine Level/Concentration)
Infant amlodipine level/concentration will be determined.
Time frame: Infant blood sample drawn at approximately 36 hours of life
Population: Of the 16 patients enrolled in the study, only 8 continued in the study and allowed their infant's to have study sampling performed.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Pregnant Women Taking Amlodipine | Drug Level/Concentration in Infant Blood (Amlodipine Level/Concentration) | NA ng/mL |
Primary
Drug Levels/Concentration in Cord Blood (Amlodipine Levels/Concentrations)
Maternal and cord blood amlodipine levels/concentrations will be determined.
Time frame: Pair maternal blood sample and cord blood sample will draw within 1 hour of delivery
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pregnant Women Taking Amlodipine | Drug Levels/Concentration in Cord Blood (Amlodipine Levels/Concentrations) | Infant cord blood plasma amlodipine concentration | 0.49 ng/mL | Standard Deviation 0.29 |
| Pregnant Women Taking Amlodipine | Drug Levels/Concentration in Cord Blood (Amlodipine Levels/Concentrations) | Maternal serum amlodipine concentration | 1.27 ng/mL | Standard Deviation 0.84 |
Primary
Half-life of Amlodipine in Maternal Plasma
The half-life of amlodipine in the maternal plasma in the peripartum period was measured.
Time frame: Maternal blood samples were obtained at 4, 6, 8, 12, 15 and 24 hours after amlodipine dosing
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pregnant Women Taking Amlodipine | Half-life of Amlodipine in Maternal Plasma | 13.7 Hours | Standard Deviation 4.9 |
Primary
Maximal Amlodipine Maternal Serum Concentration
The maximum concentration of amlodipine detected in the maternal serum in the peripartum period was measured.
Time frame: Maternal blood samples were obtained at 4, 6, 8, 12, 15 and 24 hours after amlodipine dosing
Population: Although 16 women were enrolled in the trial, only 11 had their blood drawn at the time of delivery due to limited availability of study personnel.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pregnant Women Taking Amlodipine | Maximal Amlodipine Maternal Serum Concentration | 2.0 ng/mL | Standard Deviation 1 |
Primary
Time to Maximal Concentration in the Maternal Serum.
The time to reach maximal amlodipine concentration in the maternal serum in the peripartum period was measured.
Time frame: Maternal blood samples were obtained at 4, 6, 8, 12, 15 and 24 hours after amlodipine dosing
Population: Although 16 women were enrolled in the trial, only 11 had their blood drawn at the time of delivery due to limited availability of study personnel.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pregnant Women Taking Amlodipine | Time to Maximal Concentration in the Maternal Serum. | 7.5 Hours | Standard Deviation 1.5 |
Secondary
Infant Gestational Age at Delivery.
The mean gestational age of infants born to mothers taking Amlodipine besylate 5 mg daily was collected.
Time frame: Gestational age at the time of birth
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pregnant Women Taking Amlodipine | Infant Gestational Age at Delivery. | 38.2 weeks | Standard Deviation 0.8 |
Secondary
Infant Length of Stay.
The length of stay of infants born to women taking amlodipine besylate will be collected.
Time frame: Time from birth to hospital discharge
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pregnant Women Taking Amlodipine | Infant Length of Stay. | 3.6 Days | Standard Deviation 0.5 |
Secondary
Major Infant Complications
Any major complications experienced by infants born to women taking amlodipine besylate including NICU admission, intraventricular hemorrhage, neonatal seizures, need for respiratory support and apnea were collected.
Time frame: During neonatal hospitalization
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Pregnant Women Taking Amlodipine | Major Infant Complications | Admission to the NICU | 0 Participants |
| Pregnant Women Taking Amlodipine | Major Infant Complications | Major neonatal complications (IVH, apnea, seizure) | 0 Participants |
Secondary
Neonatal Birth Weight
The neonatal weight at birth was collected.
Time frame: Neonatal weight at the time of birth.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pregnant Women Taking Amlodipine | Neonatal Birth Weight | 3281 grams | Standard Deviation 525 |