Hypertension, Pregnancy-Induced
Conditions
Keywords
Postpartum
Brief summary
This study aims to evaluate whether NSAIDs (Non-steroidal antiinflammatory drugs) administered during the postpartum period influence blood pressure in women with hypertensive disorders of pregnancy. The study design is a prospective double blinded randomized control trial with participants randomized to receive postpartum analgesic regimens with and without NSAIDs.
Detailed description
Non-steroidal antiinflammatory drugs (NSAIDs) are effective agents for the management of pain in the postpartum period. The addition of NSAIDs to post-cesarean analgesic regimen has been shown to improve post-cesarean pain and reduce opioid requirements. However, concern has been raised over use of NSAIDs in hypertensive pregnant patients, as recent evidence suggests the potential for increased blood pressure in patients with chronic hypertensive disorders receiving these agents. Notably, these studies were conducted on patients with longstanding chronic hypertension, which included males and non-pregnant females, and it is therefore unclear whether this recommendation is appropriate for patients with transient hypertensive disorders of pregnancy. This protocol describes a randomized trial to evaluate whether NSAIDs influence blood pressure parameters in patients with hypertensive disorders of pregnancy. Patients with severe hypertensive disorders of pregnancy (Severe HDP) will be studied separately from women with mild hypertensive disorders of pregnancy (Mild HDP).
Interventions
DRUGAcetaminophen
Participants will receive acetaminophen for postpartum mild pain relief
DRUGIbuprofen
Participants will receive ibuprofen for postpartum mild pain relief
Sponsors
MemorialCare Health System
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Delivery occurred at equal to or greater than 24 0/7 weeks gestational age * Patient receiving care with the Women's Perinatal Group (Maternal Fetal Medicine practice) or Obstetric Clinic resident services * Diagnosis of a hypertensive disorder of pregnancy (HDP), including the following: * Gestational hypertension * Preeclampsia without severe features * Preeclampsia with severe features * Hemolysis, Elevated Liver Enzymes, Low Platelet (HELLP) Syndrome * Eclampsia
Exclusion criteria
* Diagnosis of chronic hypertension or documentation of elevated blood pressures before 20 weeks gestational age. * Severe hypertension: Patients with at least one severe blood pressure measurement (systolic \>160mmHg or diastolic \>105mmHg) prior to randomization * Renal dysfunction (Serum creatinine measurement \>1.3mg/dL during the current pregnancy) * Low platelet count (recorded measurement \<50,000 during hospital admission) * Significant liver dysfunction (AST or ALT \>500) * Known sensitivities to ibuprofen or acetaminophen * Use of therapeutic doses of anticoagulation (low dose anticoagulation used for routine prophylaxis of venous thromboembolism is acceptable) * Postpartum hemorrhage requiring transfusion
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Average Mean Arterial Blood Pressure- Mild Group | Averaged from all blood pressures measured through study completion, an average of 3 days | Primary outcome for Hypertensive disorders of pregnancy-Mild Study Group |
| Primary Outcome for Hypertensive Disorders of Pregnancy- Severe Study Group | Through study completion, an average of 3 days | Proportion of participants with at least one episode of severe blood pressure postpartum (systolic \>=160 or diastolic \>=105mmHg) during inpatient postpartum hospitalization |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pain Control During Hospital Stay | Through study completion, an average of 3 days | Wong-Baker Facial Grimace Pain Scale Scores During Inpatient Postpartum Hospital Stay Minimum 0, maximum 10. 10 means the highest level of pain |
| Outpatient Blood Pressure Measurement | 6 weeks after discharge from the hospital | Outpatient postpartum blood pressure measurement (represented in mean arterial pressure (MAP) within 6 weeks after discharge |
| Patient Satisfaction | Through study completion, an average of 3 days | Number of patients reporting High level of satisfaction with pain medications |
| Length of Hospital Stay | Through study completion, an average of 3 days | Length of Hospital Stay after delivery |
| Diuresis | Through study completion, an average of 3 days | Achievement of average 200ml/hour for 4 consecutive hours |
| Average Mean Arterial Blood Pressures During Hospital Stay | Averaged from all blood pressures measured through study completion, an average of 3 days | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Severe HDP- NSAID This arm will be assigned a postpartum analgesic regimen with ibuprofen.
Ibuprofen: Participants will receive ibuprofen for postpartum mild pain relief | 70 |
| Mild HDP- NSAID This arm will be assigned a postpartum analgesic regimen with ibuprofen.
Ibuprofen: Participants will receive ibuprofen for postpartum mild pain relief | 31 |
| Severe HDP- No NSAID This arm will be assigned a postpartum analgesic regimen with acetaminophen.
Acetaminophen: Participants will receive acetaminophen for postpartum mild pain relief | 70 |
| Mild HDP- No NSAID This arm will be assigned a postpartum analgesic regimen with acetaminophen.
Acetaminophen: Participants will receive acetaminophen for postpartum mild pain relief | 31 |
| Total | 202 |
Baseline characteristics
| Characteristic | Severe HDP- NSAID | Total | Mild HDP- No NSAID | Severe HDP- No NSAID | Mild HDP- NSAID |
|---|---|---|---|---|---|
| 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 | 70 Participants | 202 Participants | 31 Participants | 70 Participants | 31 Participants |
| Age, Continuous | 29.9 years STANDARD_DEVIATION 5.8 | 28.5 years STANDARD_DEVIATION 6 | 28 years STANDARD_DEVIATION 5 | 29.2 years STANDARD_DEVIATION 6.5 | 28 years STANDARD_DEVIATION 6 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 37 Participants | 106 Participants | 11 Participants | 46 Participants | 12 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 33 Participants | 96 Participants | 20 Participants | 24 Participants | 19 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Gestational age | 36.4 weeks STANDARD_DEVIATION 4 | 37 weeks STANDARD_DEVIATION 1 | 38 weeks STANDARD_DEVIATION 3 | 35.4 weeks STANDARD_DEVIATION 3.7 | 37 weeks STANDARD_DEVIATION 3 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 6 Participants | 17 Participants | 3 Participants | 3 Participants | 5 Participants |
| Race (NIH/OMB) Black or African American | 16 Participants | 38 Participants | 5 Participants | 10 Participants | 7 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 2 Participants | 1 Participants | 1 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 | 1 Participants | 6 Participants | 2 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) White | 47 Participants | 139 Participants | 20 Participants | 54 Participants | 18 Participants |
| Region of Enrollment United States | 70 participants | 202 participants | 31 participants | 70 participants | 31 participants |
| Sex: Female, Male Female | 70 Participants | 202 Participants | 31 Participants | 70 Participants | 31 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 / 70 | 0 / 31 | 0 / 70 | 0 / 30 |
| other Total, other adverse events | 0 / 70 | 0 / 31 | 0 / 70 | 0 / 30 |
| serious Total, serious adverse events | 0 / 70 | 0 / 31 | 0 / 70 | 0 / 30 |
Outcome results
Primary
Average Mean Arterial Blood Pressure- Mild Group
Primary outcome for Hypertensive disorders of pregnancy-Mild Study Group
Time frame: Averaged from all blood pressures measured through study completion, an average of 3 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Mild Hypertensive Disorders of Pregnancy- NSAID | Average Mean Arterial Blood Pressure- Mild Group | 93 mmHg | Standard Deviation 8 |
| Mild Hypertensive Disorders of Pregnancy- No NSAID | Average Mean Arterial Blood Pressure- Mild Group | 93 mmHg | Standard Deviation 7 |
Primary
Primary Outcome for Hypertensive Disorders of Pregnancy- Severe Study Group
Proportion of participants with at least one episode of severe blood pressure postpartum (systolic \>=160 or diastolic \>=105mmHg) during inpatient postpartum hospitalization
Time frame: Through study completion, an average of 3 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Mild Hypertensive Disorders of Pregnancy- NSAID | Primary Outcome for Hypertensive Disorders of Pregnancy- Severe Study Group | 27 Participants |
| Mild Hypertensive Disorders of Pregnancy- No NSAID | Primary Outcome for Hypertensive Disorders of Pregnancy- Severe Study Group | 29 Participants |
Secondary
Average Mean Arterial Blood Pressures During Hospital Stay
Time frame: Averaged from all blood pressures measured through study completion, an average of 3 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Mild Hypertensive Disorders of Pregnancy- NSAID | Average Mean Arterial Blood Pressures During Hospital Stay | 95.7 mmHG | Standard Deviation 8.2 |
| Mild Hypertensive Disorders of Pregnancy- No NSAID | Average Mean Arterial Blood Pressures During Hospital Stay | 95.9 mmHG | Standard Deviation 9.5 |
Secondary
Diuresis
Achievement of average 200ml/hour for 4 consecutive hours
Time frame: Through study completion, an average of 3 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Mild Hypertensive Disorders of Pregnancy- NSAID | Diuresis | 45 Participants |
| Mild Hypertensive Disorders of Pregnancy- No NSAID | Diuresis | 19 Participants |
| Severe HDP- No NSAID | Diuresis | 46 Participants |
| Mild HDP- No NSAID | Diuresis | 23 Participants |
Secondary
Length of Hospital Stay
Length of Hospital Stay after delivery
Time frame: Through study completion, an average of 3 days
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Mild Hypertensive Disorders of Pregnancy- NSAID | Length of Hospital Stay | 4.3 days |
| Mild Hypertensive Disorders of Pregnancy- No NSAID | Length of Hospital Stay | 2.0 days |
| Severe HDP- No NSAID | Length of Hospital Stay | 3.7 days |
| Mild HDP- No NSAID | Length of Hospital Stay | 1.8 days |
Secondary
Outpatient Blood Pressure Measurement
Outpatient postpartum blood pressure measurement (represented in mean arterial pressure (MAP) within 6 weeks after discharge
Time frame: 6 weeks after discharge from the hospital
Population: There was a large attrition in participants for this outpatient outcome
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Mild Hypertensive Disorders of Pregnancy- NSAID | Outpatient Blood Pressure Measurement | 99 mmHg |
| Mild Hypertensive Disorders of Pregnancy- No NSAID | Outpatient Blood Pressure Measurement | 95 mmHg |
| Severe HDP- No NSAID | Outpatient Blood Pressure Measurement | 97.8 mmHg |
| Mild HDP- No NSAID | Outpatient Blood Pressure Measurement | 102.7 mmHg |
Secondary
Pain Control During Hospital Stay
Wong-Baker Facial Grimace Pain Scale Scores During Inpatient Postpartum Hospital Stay Minimum 0, maximum 10. 10 means the highest level of pain
Time frame: Through study completion, an average of 3 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Mild Hypertensive Disorders of Pregnancy- NSAID | Pain Control During Hospital Stay | 6.1 score on a scale | Standard Deviation 1.5 |
| Mild Hypertensive Disorders of Pregnancy- No NSAID | Pain Control During Hospital Stay | 6.4 score on a scale | Standard Deviation 1.4 |
| Severe HDP- No NSAID | Pain Control During Hospital Stay | 5.6 score on a scale | Standard Deviation 1.9 |
| Mild HDP- No NSAID | Pain Control During Hospital Stay | 6.0 score on a scale | Standard Deviation 1 |
Secondary
Patient Satisfaction
Number of patients reporting High level of satisfaction with pain medications
Time frame: Through study completion, an average of 3 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Mild Hypertensive Disorders of Pregnancy- NSAID | Patient Satisfaction | 58 Participants |
| Mild Hypertensive Disorders of Pregnancy- No NSAID | Patient Satisfaction | 22 Participants |
| Severe HDP- No NSAID | Patient Satisfaction | 65 Participants |
| Mild HDP- No NSAID | Patient Satisfaction | 22 Participants |