Treatment Targets for Chronic Hypertension in Pregnancy
| Status: | Completed |
|---|---|
| Conditions: | High Blood Pressure (Hypertension), Hospital, Women's Studies, Endocrine, Nephrology |
| Therapuetic Areas: | Cardiology / Vascular Diseases, Endocrinology, Nephrology / Urology, Other, Reproductive |
| Healthy: | No |
| Age Range: | 18 - 50 |
| Updated: | 4/2/2016 |
| Start Date: | July 2004 |
| End Date: | June 2007 |
| Contact: | Phyllis August, MD MPH |
| Email: | paugust@med.cornell.edu |
| Phone: | 212-746-2210 |
This project is a clinical study of women with high blood pressure who become pregnant.
Preeclampsia is a syndrome developing at the end of a pregnancy characterized by an abrupt
rise in blood pressure (BP), blood clotting and kidney dysfunction, and may result in
premature delivery, infant death, and maternal bleeding, kidney failure and stroke. The goal
is to determine whether lowering blood pressure to a normal pressure of 120/80 is associated
with a lower incidence of preeclampsia. Women who are completely healthy have a 5% chance of
developing preeclampsia, however women with preexisting high blood pressure have a 25%
chance of this complication. Several studies, including our own suggest that higher blood
pressure early in pregnancy (<20 weeks) is associated with an even higher risk of
preeclampsia. Currently we, the researchers at Weill Medical College of Cornell University,
do not know how to treat women with high blood pressure and/or kidney disease during
pregnancy. Keeping the BP in the normal range may be beneficial to the mother. On the other
hand, we are not sure if the blood pressure lowering or the medications may or may not have
adverse effects for the baby. Different trials to answer this question have been performed
with no clear conclusions. Because of these uncertainties, we propose to compare two
different strategies for treating women with high BP who become pregnant. We will treat half
the women with BP medications to normalize BP (120-130/80 mm Hg) (experimental group) and
the other half with the goal of keeping the BP slightly higher (140-150/90-100 mm
Hg)(standard therapy group). We will determine which approach results in healthier
pregnancies, and lower incidence of preeclampsia. Reducing the incidence of preeclampsia
would be of significant benefit to both mothers and babies.
Preeclampsia is a syndrome developing at the end of a pregnancy characterized by an abrupt
rise in blood pressure (BP), blood clotting and kidney dysfunction, and may result in
premature delivery, infant death, and maternal bleeding, kidney failure and stroke. The goal
is to determine whether lowering blood pressure to a normal pressure of 120/80 is associated
with a lower incidence of preeclampsia. Women who are completely healthy have a 5% chance of
developing preeclampsia, however women with preexisting high blood pressure have a 25%
chance of this complication. Several studies, including our own suggest that higher blood
pressure early in pregnancy (<20 weeks) is associated with an even higher risk of
preeclampsia. Currently we, the researchers at Weill Medical College of Cornell University,
do not know how to treat women with high blood pressure and/or kidney disease during
pregnancy. Keeping the BP in the normal range may be beneficial to the mother. On the other
hand, we are not sure if the blood pressure lowering or the medications may or may not have
adverse effects for the baby. Different trials to answer this question have been performed
with no clear conclusions. Because of these uncertainties, we propose to compare two
different strategies for treating women with high BP who become pregnant. We will treat half
the women with BP medications to normalize BP (120-130/80 mm Hg) (experimental group) and
the other half with the goal of keeping the BP slightly higher (140-150/90-100 mm
Hg)(standard therapy group). We will determine which approach results in healthier
pregnancies, and lower incidence of preeclampsia. Reducing the incidence of preeclampsia
would be of significant benefit to both mothers and babies.
Methods:
This is a pilot study to examine the feasibility of conducting a larger, multi center
randomized control trial. Fifty women with chronic hypertension who are pregnant and are
seen in the first trimester of pregnancy will be recruited from the offices of obstetricians
at New York Presbyterian Hospital.
Recruitment:
First trimester (up to 13 6/7th weeks)
Stratified by:
- Parity (primiparous vs. multiparous delivering a fetus >20 weeks gestation)
- Severity of hypertension (>150/95) as determined on screening antepartum visit
Inclusion Criteria:
1. Pregnant patients will be evaluated for recruitment to 13 6/7 weeks gestation.
2. Age 18-50
3. Patients will be included for consideration to enter this trial if office blood
pressure is >140/90 mm Hg: systolic >140 mm Hg, diastolic >90 mm Hg or both. The
average of 3 readings taken a minimum of 5 minutes apart will be recorded as the
baseline blood pressure.
4. Patients will also be included for consideration to enter this trial if they have known
longstanding hypertension diastolic blood pressure (DBP) >90 within 2 years of index
pregnancy and/or are on antihypertensive medication, regardless of in-office blood
pressure if seen in their first trimester.
Exclusion Criteria:
Significant target organ damage; at the patient’s initial antepartum visit, routine serum
creatinine and urine dipstick for protein are performed by the attending obstetrician. If
the patient has been hypertensive by history for over 5 years, a screening electrocardiogram
will be performed. These will be reviewed for results precluding participation in the trial.
1. Known renal disease creatinine > 1.2 mg/dl
2. Proteinuria >500 mg/day at baseline
3. Left ventricular hypertrophy by electrocardiography (ECG) criteria.
4. History of the following: chronic illness requiring immunosuppression, as well as
secondary causes of hypertension: pheochromocytoma, hyperaldosteronism, coarctation of
aorta, renal artery stenosis not revascularized.
NB: the presence of the above conditions would make it more likely that a clinician would
treat blood pressure during pregnancy. Therefore, the patient may be randomized and
treatment begun as per protocol prior to complete evaluation of presence of above
conditions; if exclusion criteria are subsequently identified the patient would then be
excluded and treated according to individual physicians standard of practice.
Enrollment:
Patients will undergo initial baseline evaluation. History and physical will be performed.
Weight, height and blood pressure will be recorded.
Eligible patients will sign informed consent. Each patient will have a data sheet for the
purpose of recording study results.
Randomization:
Patients will be randomized to one of two blood pressure targets:
120-130/80-85 mm Hg vs. 140-150/90-100 mm Hg
Randomization will occur by blocked randomization in blocks of 6. Randomization is
stratified for parity (nulliparous vs. multiparous) and severe vs. non-severe hypertension.
There are therefore 4 potential groups:
1. Nulliparous + non-severe hypertension
2. Multiparous + non-severe hypertension
3. Nulliparous + severe hypertension
4. Multiparous + severe hypertension
There are 54 envelopes for each group (allowing for the theoretic possibility that all
patients may fall into one group) and envelopes are numbered and will be opened sequentially
to allocate patients during the randomization process.
Treatment:
Patients with no prior history of hypertension will be treated as per the protocol described
below.
Patients with a known history of hypertension will still be randomized to the appropriate
group according to parity and blood pressure in clinic, but will be asked to stop their
antihypertensive medication for a wash out period.
The patient will then return to clinic three to seven days later off medication to have a
repeat blood pressure measurement. If they own a home blood pressure monitor and this has
been calibrated to office equipment, they may take their blood pressure at home.
They will be then be treated as per their randomization group i.e. to a blood pressure of
120-130/80-85 mm Hg vs. 140-150/90-100 mm Hg as per the protocol below.
The patient will be given a diary to record obstetric data and blood pressure data.
Duplicate records will be kept by the patient and physician.
Weight, blood pressure, pulse, presence or absence of edema and urinary protein will be
recorded at each visit.
Medication Protocol:
Treatment is to commence immediately after randomization unless the patient is undergoing a
washout period described above.
Some patients will initially require no medication as BP’s may be below the treatment
threshold, depending on their treatment group.
Treatment will be with methyldopa, labetolol, long acting nifedipine, hydralazine or
clonidine.
Scheduled Visits:
Patients will be followed every two to four weeks until delivery. Medication will be
titrated to achieve the desired blood pressure targets. Patients will not be billed for
these visits.
The achievement of target blood pressure will be assessed by an average of three blood
pressure measurements obtained at every six weeks visits: weeks 20, 26, 32 and 38.
At the 20 week visit, routine blood work will be drawn to evaluate uric acid and plasma
renin activity as validation of the prediction algorithm.
Home Blood Pressure Monitoring:
If patients own a home blood pressure monitor, they will be asked to bring it into clinic
for calibration. They will be given a blood pressure diary to record home blood pressure
monitoring or BP measurements done in another clinic or pharmacy.
Duration of Treatment:
The treatment goals of 120-130/80 mm Hg vs. 140-150/90 mm Hg will be applied from the time
of randomization until delivery. Postpartum, clinicians will choose their own blood pressure
goals as per JNC-7 guidelines.
Assessment of Outcomes:
For the pilot trial, maternal blood pressure is the primary outcome. This will be measured
at weeks 20, 26, 32, 36 using a standardized method: after 15 minutes of rest, blood
pressure will be measured with the woman seated, arm supported at heart level, bladder of
cuff encircling >80% of arm circumference and phase V Korotkoff used for diastolic reading.
Blood pressure will be recorded three times, five minutes apart, and the mean of these
values will allow assessment of BP control in the study.
Secondary outcomes:
1. The incidence of superimposed preeclampsia in chronically hypertensive women. Diagnosis
of superimposed preeclampsia will be made by the following criteria:
- Worsening hypertension after 20 weeks
- AND proteinuria >.3g/day on 24 hour collection when there was previously none OR
doubling of proteinuria, in those positive at baseline
- AND/OR the HELLP syndrome (hemolysis on blood smear, liver transaminase levels > 2
x normal, low platelets <100/mm3).
2. Gestational age
3. Birth weight < 10th centile for gestational age
4. Serious perinatal complications including neonatal death, respiratory distress,
intraventricular hemorrhage, hypotension, bradycardia, and maternal complications of
eclampsia, stroke, or end organ failure, cesarean section. Preterm admission, severe
hypertension and indication for delivery will also be evaluated.
This is a pilot study to examine the feasibility of conducting a larger, multi center
randomized control trial. Fifty women with chronic hypertension who are pregnant and are
seen in the first trimester of pregnancy will be recruited from the offices of obstetricians
at New York Presbyterian Hospital.
Recruitment:
First trimester (up to 13 6/7th weeks)
Stratified by:
- Parity (primiparous vs. multiparous delivering a fetus >20 weeks gestation)
- Severity of hypertension (>150/95) as determined on screening antepartum visit
Inclusion Criteria:
1. Pregnant patients will be evaluated for recruitment to 13 6/7 weeks gestation.
2. Age 18-50
3. Patients will be included for consideration to enter this trial if office blood
pressure is >140/90 mm Hg: systolic >140 mm Hg, diastolic >90 mm Hg or both. The
average of 3 readings taken a minimum of 5 minutes apart will be recorded as the
baseline blood pressure.
4. Patients will also be included for consideration to enter this trial if they have known
longstanding hypertension diastolic blood pressure (DBP) >90 within 2 years of index
pregnancy and/or are on antihypertensive medication, regardless of in-office blood
pressure if seen in their first trimester.
Exclusion Criteria:
Significant target organ damage; at the patient’s initial antepartum visit, routine serum
creatinine and urine dipstick for protein are performed by the attending obstetrician. If
the patient has been hypertensive by history for over 5 years, a screening electrocardiogram
will be performed. These will be reviewed for results precluding participation in the trial.
1. Known renal disease creatinine > 1.2 mg/dl
2. Proteinuria >500 mg/day at baseline
3. Left ventricular hypertrophy by electrocardiography (ECG) criteria.
4. History of the following: chronic illness requiring immunosuppression, as well as
secondary causes of hypertension: pheochromocytoma, hyperaldosteronism, coarctation of
aorta, renal artery stenosis not revascularized.
NB: the presence of the above conditions would make it more likely that a clinician would
treat blood pressure during pregnancy. Therefore, the patient may be randomized and
treatment begun as per protocol prior to complete evaluation of presence of above
conditions; if exclusion criteria are subsequently identified the patient would then be
excluded and treated according to individual physicians standard of practice.
Enrollment:
Patients will undergo initial baseline evaluation. History and physical will be performed.
Weight, height and blood pressure will be recorded.
Eligible patients will sign informed consent. Each patient will have a data sheet for the
purpose of recording study results.
Randomization:
Patients will be randomized to one of two blood pressure targets:
120-130/80-85 mm Hg vs. 140-150/90-100 mm Hg
Randomization will occur by blocked randomization in blocks of 6. Randomization is
stratified for parity (nulliparous vs. multiparous) and severe vs. non-severe hypertension.
There are therefore 4 potential groups:
1. Nulliparous + non-severe hypertension
2. Multiparous + non-severe hypertension
3. Nulliparous + severe hypertension
4. Multiparous + severe hypertension
There are 54 envelopes for each group (allowing for the theoretic possibility that all
patients may fall into one group) and envelopes are numbered and will be opened sequentially
to allocate patients during the randomization process.
Treatment:
Patients with no prior history of hypertension will be treated as per the protocol described
below.
Patients with a known history of hypertension will still be randomized to the appropriate
group according to parity and blood pressure in clinic, but will be asked to stop their
antihypertensive medication for a wash out period.
The patient will then return to clinic three to seven days later off medication to have a
repeat blood pressure measurement. If they own a home blood pressure monitor and this has
been calibrated to office equipment, they may take their blood pressure at home.
They will be then be treated as per their randomization group i.e. to a blood pressure of
120-130/80-85 mm Hg vs. 140-150/90-100 mm Hg as per the protocol below.
The patient will be given a diary to record obstetric data and blood pressure data.
Duplicate records will be kept by the patient and physician.
Weight, blood pressure, pulse, presence or absence of edema and urinary protein will be
recorded at each visit.
Medication Protocol:
Treatment is to commence immediately after randomization unless the patient is undergoing a
washout period described above.
Some patients will initially require no medication as BP’s may be below the treatment
threshold, depending on their treatment group.
Treatment will be with methyldopa, labetolol, long acting nifedipine, hydralazine or
clonidine.
Scheduled Visits:
Patients will be followed every two to four weeks until delivery. Medication will be
titrated to achieve the desired blood pressure targets. Patients will not be billed for
these visits.
The achievement of target blood pressure will be assessed by an average of three blood
pressure measurements obtained at every six weeks visits: weeks 20, 26, 32 and 38.
At the 20 week visit, routine blood work will be drawn to evaluate uric acid and plasma
renin activity as validation of the prediction algorithm.
Home Blood Pressure Monitoring:
If patients own a home blood pressure monitor, they will be asked to bring it into clinic
for calibration. They will be given a blood pressure diary to record home blood pressure
monitoring or BP measurements done in another clinic or pharmacy.
Duration of Treatment:
The treatment goals of 120-130/80 mm Hg vs. 140-150/90 mm Hg will be applied from the time
of randomization until delivery. Postpartum, clinicians will choose their own blood pressure
goals as per JNC-7 guidelines.
Assessment of Outcomes:
For the pilot trial, maternal blood pressure is the primary outcome. This will be measured
at weeks 20, 26, 32, 36 using a standardized method: after 15 minutes of rest, blood
pressure will be measured with the woman seated, arm supported at heart level, bladder of
cuff encircling >80% of arm circumference and phase V Korotkoff used for diastolic reading.
Blood pressure will be recorded three times, five minutes apart, and the mean of these
values will allow assessment of BP control in the study.
Secondary outcomes:
1. The incidence of superimposed preeclampsia in chronically hypertensive women. Diagnosis
of superimposed preeclampsia will be made by the following criteria:
- Worsening hypertension after 20 weeks
- AND proteinuria >.3g/day on 24 hour collection when there was previously none OR
doubling of proteinuria, in those positive at baseline
- AND/OR the HELLP syndrome (hemolysis on blood smear, liver transaminase levels > 2
x normal, low platelets <100/mm3).
2. Gestational age
3. Birth weight < 10th centile for gestational age
4. Serious perinatal complications including neonatal death, respiratory distress,
intraventricular hemorrhage, hypotension, bradycardia, and maternal complications of
eclampsia, stroke, or end organ failure, cesarean section. Preterm admission, severe
hypertension and indication for delivery will also be evaluated.
Inclusion Criteria:
1. Pregnant patients will be evaluated for recruitment to 13 6/7 weeks gestation.
2. Age 18-50
3. Patients will be included for consideration to enter this trial if office blood
pressure is >140/90 mm Hg: systolic >140 mm Hg, diastolic >90 mm Hg or both. The
average of 3 readings taken a minimum of 5 minutes apart will be recorded as the
baseline blood pressure.
4. Patients will also be included for consideration to enter this trial if they have
known longstanding hypertension DBP >90 within 2 years of index pregnancy and/or are
on antihypertensive medication, regardless of in-office blood pressure if seen in
their first trimester.
Exclusion Criteria:
Significant target organ damage; at the patient’s initial antepartum visit, routine serum
creatinine and urine dipstick for protein are performed by the attending obstetrician. If
the patient has been hypertensive by history for over 5 years, a screening
electrocardiogram will be performed. These will be reviewed for results precluding
participation in the trial.
1. Known renal disease creatinine > 1.2 mg/dl
2. Proteinuria >500 mg/day at baseline
3. Left ventricular hypertrophy by ECG criteria.
4. History of the following: chronic illness requiring immunosuppression, as well as
secondary causes of hypertension: pheochromocytoma, hyperaldosteronism, coarctation
of aorta, renal artery stenosis not revascularized.
We found this trial at
1
site
New York, New York 10021
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