Gestational Hypertension
Conditions
Keywords
hypertension, pregnancy, antihypertensive therapy, perinatal outcome, maternal outcome, Non-severe, non-proteinuric pre-existing or gestational hypertension in pregnancy
Brief summary
The investigators do not know which approach to treatment of non-severe high blood pressure in pregnancy is better for women and babies. In the CHIPS Trial, the investigators seek to determine whether 'less tight' control (aiming for a diastolic blood pressure \[dBP\] of 100 mmHg), compared with 'tight' control (aiming for a diastolic blood pressure \[dBP\] of 85 mmHg) can decrease the risks of adverse baby outcomes without increasing the risk of problems for the mother.
Detailed description
Primary research question: For pregnant women with non-severe, non-proteinuric maternal hypertension at 14-33 weeks, will 'less tight' control (target diastolic blood pressure \[dBP\] of 100 mmHg) versus 'tight' control (target dBP of 85 mmHg) increase (or decrease) the likelihood of pregnancy loss or Neonatal Intensive Care Unit (NICU) admission for greater than 48 hours? Secondary research question: Will 'less tight' versus 'tight' control increase (or decrease) the likelihood of serious maternal complications? Other research questions: Will 'less tight' versus 'tight' control: 1. Increase (or decrease) the likelihood of serious perinatal complications? 2. Increase (or decrease) the likelihood of severe hypertension and pre-eclampsia? 3. Increase (or decrease) the likelihood of maternal satisfaction with care? 4. Result in significant changes in dBP or health care costs? Treatment Allocation: Eligible women will be randomised centrally to either 'less tight' control (aiming for dBP of 100mmHg) or 'tight' control (aiming for dBP of 85mmHg) of their hypertension. Randomisation will be stratified by centre and type of hypertension (pre-existing or gestational). * In the 'less tight' control group, if dBP is ≥105mmHg, then antihypertensive medication must be started or increased in dose. * In the 'tight' control group, if dBP is ≤80mmHg, then antihypertensive medication must be decreased in dose or discontinued. * In both groups, centres will provide their usual care. Data will be collected on potential co-interventions (e.g., hospitalisation, bedrest). Outcomes: Primary: Pregnancy loss (miscarriage or ectopic pregnancy, pregnancy termination, stillbirth, or neonatal death) or high level neonatal care for \>48 hours in the first 28 days of life or prior to primary hospital discharge, whichever is later. Secondary: One/more serious maternal complication(s) until six weeks postpartum. Follow-up: Compliance (dBP and antihypertensive dose) will be assessed within 4 weeks of randomisation. Outcome data will be collected during the woman's (and baby's) hospital stay for birth (or loss). Women will be contacted 6 to 12 weeks after delivery (or loss) and, for preterm babies, when the baby is at 36 weeks corrected gestational age to enquire about satisfaction with care and any major maternal/neonatal morbidity following hospital discharge.
Interventions
PROCEDUREIntervention is blood pressure management approach
1\) 'Less tight' control. The dBP treatment goal is 100 mmHg. For safety, if dBP is \>105 mmHg, then antihypertensive medication must be started or increased in dose. For dBP \<100 mmHg, antihypertensive therapy should be decreased in dose or stopped, as appropriate. The intervention will be applied until delivery.
PROCEDUREIntervention is blood pressure management approach.
'Tight' control. The dBP treatment goal is 85 mmHg. For safety, if dBP is \<80 mmHg, then antihypertensive medication must be decreased in dose or discontinued. If dBP is \>85 mmHg, then antihypertensive therapy should be started or increased in dose. The intervention will be applied until delivery.
Sponsors
Canadian Institutes of Health Research (CIHR)
Sunnybrook Research Institute
University of British Columbia
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Healthy volunteers
No
Inclusion criteria
1. Pre-existing or gestational hypertension (pre-existing hypertension is dBP greater than or equal to 90 mmHg before pregnancy or 20 weeks' gestation; gestational hypertension is dBP greater than or equal to 90 mmHg that develops after 20 weeks) 2. dBP of 90 - 105 mmHg if NOT TAKING antihypertensive therapy, or dBP of 85 - 105 mmHg if TAKING antihypertensive therapy 3. Live foetus (confirmed by Doptone assessment of foetal heart tones within one week before randomisation) 4. Gestational age 14 - 33+6 weeks (as measured by last menstrual period or dating ultrasound)
Exclusion criteria
1. Severe systolic hypertension (defined as a systolic blood pressure \[sBP\] greater than or equal to 160 mmHg at randomisation) 2. Proteinuria (defined as greater than or equal to 0.3 g/d by 24 hour urine collection, or if a 24 hour urine collection is not available, by a urinary protein:creatinine ratio of greater than or equal to 30 mg/mmol or urinary dipstick of greater than or equal to 2+) 3. Use of an angiotensin converting enzyme (ACE) inhibitor at greater than or equal to 14+0 weeks' gestation 4. Contraindication to either arm of the trial or to pregnancy prolongation 5. Known multiple gestation 6. Known lethal or major foetal anomaly 7. Plan to terminate pregnancy 8. Prior participation in CHIPS
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pregnancy Loss or NICU Admission for Greater Than 48 Hours | 6 weeks | Pregnancy loss or NICU admission for greater than 48 hours, as recorded in the maternal and infant medical records immediately following the birth (or pregnancy loss), and then again after the mothers' and infants' discharge home. Supplemental information, about potential post-discharge maternal or neonatal morbidities in the 6 weeks following birth for the mother, or 28 days of life for the baby, will be obtained by contacting women at 6 weeks postpartum and/or from medical records. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Serious Maternal Complications Measured up to 6 Weeks Postpartum | 6 weeks | Serious maternal complications measured up to 6 weeks postpartum. Death or one or more life-threatening maternal complications: 1. Adverse neurological complications (stroke, eclampsia, and/or blindness), and/or 2. End-organ failure (uncontrolled hypertension, inotropic support, pulmonary oedema, respiratory failure, myocardial ischaemia/infarction, renal failure, coagulopathy, and/or transfusion) |
Countries
Argentina, Australia, Brazil, Canada, Chile, Colombia, Estonia, Hungary, Israel, Jordan, Netherlands, New Zealand, Poland, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 'Less Tight' Control. The diastolic blood pressure (dBP) treatment goal is 100 mmHg.
Intervention is blood pressure management approach: 1) 'Less tight' control. The dBP treatment goal is 100 mmHg. For safety, if dBP is \>105 mmHg, then antihypertensive medication must be started or increased in dose. For dBP \<100 mmHg, antihypertensive therapy should be decreased in dose or stopped, as appropriate. The intervention will be applied until delivery. | 497 |
| 'Tight' Control. The diastolic blood pressure (dBP) treatment goal is 85 mmHg.
Intervention is blood pressure management approach.: 'Tight' control. The dBP treatment goal is 85 mmHg. For safety, if dBP is \<80 mmHg, then antihypertensive medication must be decreased in dose or discontinued. If dBP is \>85 mmHg, then antihypertensive therapy should be started or increased in dose. The intervention will be applied until delivery. | 490 |
| Total | 987 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 2 | 1 |
| Overall Study | Withdrawal by Subject | 2 | 1 |
Baseline characteristics
| Characteristic | 'Less Tight' Control. | 'Tight' Control. | Total |
|---|---|---|---|
| Age, Continuous | 34.0 years STANDARD_DEVIATION 5.7 | 33.7 years STANDARD_DEVIATION 5.8 | 33.8 years STANDARD_DEVIATION 5.8 |
| Antihypertensive medication at enrollment | 279 participants | 287 participants | 566 participants |
| Blood pressure within 1 wk before randomization Diastolic | 92.6 mmHg STANDARD_DEVIATION 4.8 | 92.2 mmHg STANDARD_DEVIATION 5.2 | 92.4 mmHg STANDARD_DEVIATION 5 |
| Blood pressure within 1 wk before randomization Systolic | 140.4 mmHg STANDARD_DEVIATION 9.7 | 139.7 mmHg STANDARD_DEVIATION 9.8 | 140.1 mmHg STANDARD_DEVIATION 9.8 |
| Body-mass index 18.5-24.9 kg/m^2 | 116 participants | 112 participants | 228 participants |
| Body-mass index <18.5 kg/m^2 | 1 participants | 2 participants | 3 participants |
| Body-mass index 25.0-29.9 kg/m^2 | 131 participants | 135 participants | 266 participants |
| Body-mass index ≥30.0 kg/m^2 | 245 participants | 236 participants | 481 participants |
| Cigarette smoking during this pregnancy | 35 participants | 28 participants | 63 participants |
| Currently monitoring blood pressure at home | 185 participants | 194 participants | 379 participants |
| Gender Female | 497 Participants | 490 Participants | 987 Participants |
| Gender Male | 0 Participants | 0 Participants | 0 Participants |
| Gestational diabetes at enrollment | 32 participants | 31 participants | 63 participants |
| Nulliparous | 161 participants | 168 participants | 329 participants |
| Prior blood pressure ≥160 mm Hg systolic or ≥110 mm Hg diastolic during this pregnancy | 82 participants | 59 participants | 141 participants |
| Type of nonproteinuric hypertension Gestational hypertension | 126 participants | 125 participants | 251 participants |
| Type of nonproteinuric hypertension Preexisting hypertension | 371 participants | 365 participants | 736 participants |
| Weeks of gestation | 23.7 weeks STANDARD_DEVIATION 6.3 | 24.2 weeks STANDARD_DEVIATION 6.3 | 23.9 weeks STANDARD_DEVIATION 6.3 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 241 / 493 | 223 / 488 |
| serious Total, serious adverse events | 155 / 493 | 150 / 488 |
Outcome results
Primary
Pregnancy Loss or NICU Admission for Greater Than 48 Hours
Pregnancy loss or NICU admission for greater than 48 hours, as recorded in the maternal and infant medical records immediately following the birth (or pregnancy loss), and then again after the mothers' and infants' discharge home. Supplemental information, about potential post-discharge maternal or neonatal morbidities in the 6 weeks following birth for the mother, or 28 days of life for the baby, will be obtained by contacting women at 6 weeks postpartum and/or from medical records.
Time frame: 6 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 'Less Tight' Control. | Pregnancy Loss or NICU Admission for Greater Than 48 Hours | 155 participants |
| 'Tight' Control. | Pregnancy Loss or NICU Admission for Greater Than 48 Hours | 150 participants |
Comparison: We estimated that with a sample size of 514 per group, the study would have 80% power, at a two-tailed alpha level of 0.05, assuming primary outcome rates of 33% in the tight-control group and 25% in the less-tight-control group, a 10% rate of crossover, a 1% loss to follow-up, and two interim analyses, as calculated with the chi-square test with the use of East software (Cytel) and the Lan-DeMets spending function with O'Brien-Fleming-type boundaries for early stopping.95% CI: [0.77, 1.35]
Secondary
Serious Maternal Complications Measured up to 6 Weeks Postpartum
Serious maternal complications measured up to 6 weeks postpartum. Death or one or more life-threatening maternal complications: 1. Adverse neurological complications (stroke, eclampsia, and/or blindness), and/or 2. End-organ failure (uncontrolled hypertension, inotropic support, pulmonary oedema, respiratory failure, myocardial ischaemia/infarction, renal failure, coagulopathy, and/or transfusion)
Time frame: 6 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 'Less Tight' Control. | Serious Maternal Complications Measured up to 6 Weeks Postpartum | 18 participants |
| 'Tight' Control. | Serious Maternal Complications Measured up to 6 Weeks Postpartum | 10 participants |
95% CI: [0.79, 3.84]