Ignite Creation Date:
2024-05-05 @ 11:57 AM
Last Modification Date:
2024-10-26 @ 9:17 AM
Study NCT ID:
NCT00194974
Status:
WITHDRAWN
Last Update Posted:
2017-01-30
First Post:
2005-09-13
Brief Title:
Treatment Targets for Chronic Hypertension in Pregnancy
Sponsor:
Weill Medical College of Cornell University
Organization:
Weill Medical College of Cornell University
Study Overview
Official Title:
Treatment Targets for Chronic Hypertension in Pregnancy
Status:
WITHDRAWN
Status Verified Date:
2017-01
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Lack of funding
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
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 12080 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 andor 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 120-13080 mm Hg experimental group and the other half with the goal of keeping the BP slightly higher 140-15090-100 mm Hgstandard 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
Detailed Description:
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 67th weeks
Stratified by
Parity primiparous vs multiparous delivering a fetus 20 weeks gestation
Severity of hypertension 15095 as determined on screening antepartum visit
Inclusion Criteria
1 Pregnant patients will be evaluated for recruitment to 13 67 weeks gestation
2 Age 18-50
3 Patients will be included for consideration to enter this trial if office blood pressure is 14090 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 andor are on antihypertensive medication regardless of in-office blood pressure if seen in their first trimester
Exclusion Criteria
Significant target organ damage at the patients 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 12 mgdl
2 Proteinuria 500 mgday 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
120-13080-85 mm Hg vs 140-15090-100 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 ie to a blood pressure of 120-13080-85 mm Hg vs 140-15090-100 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 BPs 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 120-13080 mm Hg vs 140-15090 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 3gday on 24 hour collection when there was previously none OR doubling of proteinuria in those positive at baseline
ANDOR the HELLP syndrome hemolysis on blood smear liver transaminase levels 2 x normal low platelets 100mm3
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 67th weeks
Stratified by
Parity primiparous vs multiparous delivering a fetus 20 weeks gestation
Severity of hypertension 15095 as determined on screening antepartum visit
Inclusion Criteria
1 Pregnant patients will be evaluated for recruitment to 13 67 weeks gestation
2 Age 18-50
3 Patients will be included for consideration to enter this trial if office blood pressure is 14090 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 andor are on antihypertensive medication regardless of in-office blood pressure if seen in their first trimester
Exclusion Criteria
Significant target organ damage at the patients 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 12 mgdl
2 Proteinuria 500 mgday 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
120-13080-85 mm Hg vs 140-15090-100 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 ie to a blood pressure of 120-13080-85 mm Hg vs 140-15090-100 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 BPs 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 120-13080 mm Hg vs 140-15090 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 3gday on 24 hour collection when there was previously none OR doubling of proteinuria in those positive at baseline
ANDOR the HELLP syndrome hemolysis on blood smear liver transaminase levels 2 x normal low platelets 100mm3
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
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None