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Chronic Hypertension and Pregnancy (CHAP) Project (CHAP)

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ClinicalTrials.gov Identifier: NCT02299414
Recruitment Status : Recruiting
First Posted : November 24, 2014
Last Update Posted : November 6, 2019
Sponsor:
Collaborators:
Columbia University
Drexel University College of Medicine
Rutgers, The State University of New Jersey
Lehigh Valley Hospital
Saint Peters University Hospital
Christiana Care Health Services
Washington University School of Medicine
Duke University
University of Texas Southwestern Medical Center
The University of Texas Health Science Center, Houston
Stanford University
University of Pennsylvania
The University of Texas Medical Branch, Galveston
University of Utah
Intermountain Health Care, Inc.
University of California, San Francisco
Johns Hopkins University
University of Pittsburgh
Ochsner Health System
University of North Carolina, Chapel Hill
National Heart, Lung, and Blood Institute (NHLBI)
WakeMed Health and Hospitals
San Francisco General Hospital
McKay-Dee Hospital
Winthrop University Hospital
New York Hospital Queens
Latter Day Saints Hospital
Lyndon B Johnson General Hospital
Virtua Medical Group
Bayview Medical Center
Duke Regional Hospital
Utah Valley Regional Medical Center
Northwestern
Brown (WIHRI)
Baylor College of Medicine
Case Western/Metro Health
Ohio State University
University of Iowa
University of California, San Diego
Indiana University
Unity Point Health-Meriter Hospital WI
Weill Medical College of Cornell University
University of Oklahoma
Medical University of South Carolina
Beaumont Hospital
University of Colorado, Denver
University of Kansas Medical Center
Denver Health and Hospital Authority
Gundersen Health System
Aurora Health Care
Oregon Health and Science University
Medical College of Wisconsin
Temple University
New Jersey Medical School
University of South Alabama
Vanderbilt University
University of Arkansas
Miami Valley Hospital
Emory University
St. Luke's Hospital and Health Network, Pennsylvania
Cleveland Clinic Fairview Hospital
University of Tennessee Health Science Center
TriHealth Inc.
Cleveland Clinic Hillcrest Hospital
Tulane University
Yale University
Arrowhead Regional Medical Center
Geisinger Clinic
Information provided by (Responsible Party):
Alan Tita, University of Alabama at Birmingham

Tracking Information
First Submitted Date  ICMJE October 28, 2014
First Posted Date  ICMJE November 24, 2014
Last Update Posted Date November 6, 2019
Study Start Date  ICMJE June 2015
Estimated Primary Completion Date June 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 5, 2015)
  • Composite adverse perinatal outcome [ Time Frame: Up to 2 weeks after delivery ]
    One of more severe outcomes including fetal or neonatal death up to 2 weeks; preeclampsia with severe features (Severe hypertension and proteinuria or hypertension and severe features per ACOG); placental abruption; or indicated PTB <35 weeks (not due to spontaneous preterm labor or membrane rupture).
  • Small for Gestational Age [ Time Frame: Until delivery ]
    Birth weight less than 10th percentile for gestational age at birth according to accepted national standard
Original Primary Outcome Measures  ICMJE
 (submitted: November 19, 2014)
  • Composite adverse perinatal outcome [ Time Frame: Up to 3 months after delivery ]
    One of more severe outcomes including fetal or neonatal death up to 3 months; preeclampsia with severe features (by ACOG definition); placental abruption; or indicated PTB <35 weeks (not due to spontaneous preterm labor or membrane rupture).
  • Small for Gestational Age [ Time Frame: Until delivery ]
    Birth weight less than 10th percentile for gestational age at birth according to accepted national standard
Change History Complete list of historical versions of study NCT02299414 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: November 5, 2015)
  • Composite of maternal death or severe cardiovascular morbidity [ Time Frame: Up to 6 weeks (4-12 weeks) after delivery ]
    One or more of maternal death, heart failure, stroke, encephalopathy, Myocardial infarction or ischemia, pulmonary edema, ICU admission, or renal failure
  • Composite of severe adverse perinatal outcome [ Time Frame: Up to 6 weeks (4-12 weeks) after delivery ]
    One or more of perinatal death, IVH III or IV, BPD or chronic lung disease, NEC, ROP, Seizures, Proven sepsis
  • Adherence to treatment after delivery [ Time Frame: Up to 6 weeks (4-12 weeks) after delivery ]
    Adherence to antihypertensive therapy after delivery
Original Secondary Outcome Measures  ICMJE
 (submitted: November 19, 2014)
  • Composite of maternal death or severe cardiovascular morbidity [ Time Frame: Up to 3 months after delivery ]
    One or more of maternal death, heart failure, stroke, encephalopathy, Myocardial infarction or ischemia, pulmonary edema, ICU admission, or renal failure
  • Composite of severe adverse perinatal outcome [ Time Frame: Up to 12 weeks after delivery ]
    One or more of perinatal death, IVH III or IV, BPD or chronic lung disease, NEC, ROP, Seizures, Proven sepsis
  • Adherence to treatment after delivery [ Time Frame: Up to 12 weeks after delivery ]
    Adherence to antihypertensive therapy after delivery
Current Other Pre-specified Outcome Measures
 (submitted: November 5, 2015)
  • Preeclampsia [ Time Frame: Up to 2 weeks after delivery ]
    Mild or severe, including eclampsia
  • Superimposed gestational hypertension [ Time Frame: Enrollment (between 6 and 18 weeks gestation) to delivery ]
    Persistent hypertension above baseline without proteinuria occurring after 20 weeks gestation
  • Severe hypertension [ Time Frame: Up to 6 weeks (4-12 weeks) after delivery ]
    Blood pressure ≥160/110
  • Cesarean delivery [ Time Frame: Until delivery ]
    Cesarean delivery
  • Preterm birth [ Time Frame: At birth ]
    Delivery at <37 weeks
  • NICU admission [ Time Frame: Up to 6 weeks (4-12 weeks) after delivery ]
    NICU admission and length of NICU stay
  • Low birth weight [ Time Frame: At birth ]
    Birth weight <2500g
  • Ponderal index [ Time Frame: At birth ]
    Mean ponderal index
  • Head circumference [ Time Frame: At birth ]
    Mean head circumference
  • Placental weight [ Time Frame: At delivery ]
    Mean placental weight
  • Hypoglycemia [ Time Frame: From delivery to hospital discharge (2 - 3 days after delivery) ]
    Prevalence of hypoglycemia
  • Bradycardia [ Time Frame: From delivery to hospital discharge (2 - 3 days after delivery) ]
    Prevalence of bradycardia
  • Hypotension [ Time Frame: From delivery to hospital discharge (2 - 3 days after delivery) ]
    Incidence (%) with hypotension
  • Respiratory distress syndrome (RDS) [ Time Frame: From delivery to hospital discharge (2 - 3 days after delivery) ]
    Incidence (%) with RDS
  • Bronchopulmonary dysplasia (BPD) [ Time Frame: Up to 3 months after delivery ]
    Incidence (%) with BPD
  • Intubation/ventilation [ Time Frame: From delivery to hospital discharge (2 - 3 days after delivery) ]
    Incidence (%) with intubation for ventilation
  • Intraventricular hemorrhage (IVH) [ Time Frame: From delivery to hospital discharge (2 - 3 days after delivery) ]
    Incidence (%) with any IVH and with IVH Grades III and IV
  • Necrotizing enterocolitis (NEC) [ Time Frame: Up to 3 months after delivery ]
    Incidence (%) with NEC
  • Hyperbilirubinemia [ Time Frame: From delivery to hospital discharge (2 - 3 days after delivery) ]
    Incidence (%) with hyperbilirubinemia
  • 5-min Apgar score [ Time Frame: At delivery ]
    Apgar score <7
  • Sepsis [ Time Frame: From delivery to hospital discharge (2 - 3 days after delivery) ]
    Incidence (%) with sepsis
  • Unscheduled prenatal clinic or ER visits [ Time Frame: Up to 3 months after delivery ]
    Number of unscheduled clinic or ER visits before and after delivery
  • Hospitalizations [ Time Frame: Up to 3 months postpartum ]
    Number of hospitalizations before or after delivery
  • Postpartum unscheduled or ER visits [ Time Frame: Up to 3 months after delivery ]
    Number of postpartum unscheduled or ER visits
  • Postpartum hospitalizations [ Time Frame: Up to 3 months after delivery ]
    Number of postpartum hospitalizations
Original Other Pre-specified Outcome Measures
 (submitted: November 19, 2014)
  • Preeclampsia [ Time Frame: Up to 1 week after delivery ]
    Mild or severe, including eclampsia
  • Superimposed gestational hypertension [ Time Frame: Up to one week after delivery ]
    Persistent hypertension above baseline without proteinuria occurring after 20 weeks gestation
  • Maternal systolic and diastolic blood pressure [ Time Frame: Until delivery ]
    Mean change in serial blood pressure values pregnancy
  • Severe hypertension [ Time Frame: Up to 3 months after delivery ]
    Blood pressure ≥160/110
  • Cesarean delivery [ Time Frame: Until delivery ]
    Cesarean delivery
  • Preterm birth [ Time Frame: At birth ]
    Delivery at <37 weeks
  • NICU admission [ Time Frame: Up to 3 months after delivery ]
    NICU admission and length of NICU stay
  • Low birth weight [ Time Frame: At birth ]
    Birth weight <2500g
  • Ponderal index [ Time Frame: At birth ]
    Mean ponderal index
  • Head circumference [ Time Frame: At birth ]
    Mean head circumference
  • Placental weight [ Time Frame: At delivery ]
    Mean placental weight
  • Hypoglycemia [ Time Frame: Up to 3 months after delivery ]
    Prevalence of hypoglycemia
  • Bradycardia [ Time Frame: Up to 3 months after delivery ]
    Prevalence of bradycardia
  • Hypotension [ Time Frame: Up to 3 months after delivery ]
    Incidence (%) with hypotension
  • Respiratory distress syndrome (RDS) [ Time Frame: Up to 1 week after delivery ]
    Incidence (%) with RDS
  • Bronchopulmonary dysplasia (BPD) [ Time Frame: Up to 3 months after delivery ]
    Incidence (%) with BPD
  • Intubation/ventilation [ Time Frame: Up to 3 months after delivery ]
    Incidence (%) with intubation for ventilation
  • Intraventricular hemorrhage (IVH) [ Time Frame: Up to 3 months after delivery ]
    Incidence (%) with any IVH and with IVH Grades III and IV
  • Necrotizing enterocolitis (NEC) [ Time Frame: Up to 3 months after delivery ]
    Incidence (%) with NEC
  • Hyperbilirubinemia [ Time Frame: Up to 3 months after delivery ]
    Incidence (%) with hyperbilirubinemia
  • 5-min Apgar score [ Time Frame: At delivery ]
    Apgar score <7
  • Sepsis [ Time Frame: Up to 3 months after delivery ]
    Incidence (%) with sepsis
  • Unscheduled prenatal clinic or ER visits [ Time Frame: Up to 3 months after delivery ]
    Number of unscheduled clinic or ER visits before and after delivery
  • Hospitalizations [ Time Frame: Up to 3 months postpartum ]
    Number of hospitalizations before or after delivery
  • Postpartum unscheduled or ER visits [ Time Frame: Up to 3 months after delivery ]
    Number of postpartum unscheduled or ER visits
  • Postpartum hospitalizations [ Time Frame: Up to 3 months after delivery ]
    Number of postpartum hospitalizations
 
Descriptive Information
Brief Title  ICMJE Chronic Hypertension and Pregnancy (CHAP) Project
Official Title  ICMJE A Pragmatic Multicenter Randomized Clinical Trial (RCT) of Antihypertensive Therapy for Mild Chronic Hypertension During Pregnancy: Chronic Hypertension and Pregnancy (CHAP) Project
Brief Summary The purpose of this study is to evaluate whether a blood pressure treatment strategy during pregnancy to achieve targets that are recommended for non-pregnant reproductive-age adults (<140/90 mmHg) compared ACOG- recommended standard during pregnancy (no treatment unless BP is severe) is effective and safe.
Detailed Description

During pregnancy, chronic hypertension (CHTN) is the most common major medical disorder encountered, occurring in 2-6%. The substantial negative effect of CHTN on pregnancy includes a consistent 3- to 5-fold increase in superimposed preeclampsia and adverse perinatal outcomes (fetal or neonatal death, preterm birth -PTB, poor fetal growth and placental abruption) and possibly a 5- to10-fold increase in maternal cardiovascular and other complications (death, cerebrovascular accident, pulmonary edema and acute renal failure). Mild CHTN (BP <160/110) contributes to a large proportion of these adverse outcomes. While antihypertensive treatment of CHTN is standard for the general population, it is uncertain whether treatment during pregnancy reduces maternal or fetal complications, and there are concerns that decreased arterial pressure may reduce fetal blood flow and cause poor fetal growth or small-for-gestational-age (SGA) infants. Some authorities, including the American College of Obstetricians and Gynecologists (ACOG) and American Society of Hypertension (ASH) recommend withholding antihypertensive therapy for mild CHTN, particularly if BP is <160/105-110 mmHg. The recommendation to withhold antihypertensive treatment in pregnancy conflicts with the broader public health goal to reduce BP in those with CHTN and there is no evidence that discontinuing therapy during the brief period of pregnancy affects maternal outcomes (other than reducing the severe hypertension). For over a decade, authorities have consistently called for well-designed and powered trials to delineate the benefits and risks of pharmacologic therapy for CHTN during pregnancy.

Therefore, our multicenter consortium proposes the Chronic Hypertension and Pregnancy (CHAP) Project, a large pragmatic randomized trial with a primary aim to evaluate the benefits and harms of pharmacologic treatment of mild CHTN in pregnancy.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Hypertension
Intervention  ICMJE
  • Drug: Anti-hypertensive therapy
    1st line anti-hypertensive (Labetalol or Nifedipine ER) started; escalate to maximum dose and a preferred 2nd line medication if needed (nifedipine ER or Labetalol)
    Other Names:
    • Normodyne
    • Trandate
    • Procardia XL
    • Adalat
  • Other: No anti-hypertensive therapy (unless BP is severe)
    Treatment will not be started if blood pressure remains <160/105; for blood pressure ≥160/105, treatment with labetalol or Nifedipine ER will be initiated and maintained at lowest dose needed to keep blood pressure under 160/105.
Study Arms  ICMJE
  • Experimental: Anti-hypertensive therapy to goal <140/90 mmHg
    Labetalol or Nifedipine ER will be used as first-line to achieve goal; if necessary Nifedipine ER or Labetalol will be second-line antihypertensive. Rarely, other antihypertensive medications may also be used
    Intervention: Drug: Anti-hypertensive therapy
  • Active Comparator: No anti-hypertensive unless BP is severe (≥160/105 mmHg
    Antihypertensive therapy given only if BP becomes severe (defined as BP ≥160/105). The lowest dose of anti-hypertensive needed to keep blood pressure below this threshold will be given (1st-line - Labetalol or Nifedipine ER and 2nd-line - Labetalol or Nifedipine ER). Rarely other medications may be used
    Intervention: Other: No anti-hypertensive therapy (unless BP is severe)
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: March 13, 2019)
2404
Original Estimated Enrollment  ICMJE
 (submitted: November 19, 2014)
4700
Estimated Study Completion Date  ICMJE June 2022
Estimated Primary Completion Date June 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Women with chronic hypertension in pregnancy with new or untreated chronic hypertension, blood pressure 140-159 systolic or 90-104 diastolic OR known chronic hypertension on monotherapy and taking any antihypertensive and blood pressure ≤159/104 (including those with blood pressure <140/90);
  2. Singleton; and
  3. viable pregnancy <23 weeks of gestation.

Exclusion Criteria:

  1. Blood pressures prior to randomization ≥160 systolic or ≥105 diastolic (with or without treatment);
  2. Patients currently treated with >1 antihypertensive medication (more likely to have severe chronic hypertension);
  3. Multi-fetal pregnancy;
  4. Known secondary cause of chronic hypertension;
  5. High-risk co-morbidities for which treatment may be indicated:

    • Class C or higher diabetes mellitus
    • Chronic kidney disease - including baseline proteinuria (>300mg/24-hr, p/c ratio >0.3, or persistent 1+ proteinuria*) or creatinine >1.2.

      *If a dipstick value at screening is more than trace, a clean catch or catheter urine should be obtained and re-tested by dipstick. If this shows trace or absence of protein, the patient is included. If it again shows 1+ protein, the patient is excluded until a 24-hr urine <300mg/24hr or p/c ratio is <0.3.

    • Cardiac disorders: cardiomyopathy, angina, CAD
    • Prior stroke
    • Retinopathy
    • Sickle cell disease;
  6. Known major fetal anomaly;
  7. Known fetal demise;
  8. Suspected IUGR;
  9. Membrane rupture or planned termination prior to randomization;
  10. Plan to deliver outside the consortium centers (unless approved by the Clinical Coordinating Center) or unlikely to follow-up in the opinion of study staff or previous participation in this trial;
  11. Contraindication to labetalol or nifedipine (e.g. know hypersensitivity); and (12) Current substance abuse or addiction (cocaine, methamphetamine) *The minimum age varies by center
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 12 Years and older   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Alan Tita, MD, PhD 205-934-5612 atita@uabmc.edu
Contact: Michelle Feese, MPH 205-975-8633 mfeese@uab.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02299414
Other Study ID Numbers  ICMJE 1U01HL119242-01( U.S. NIH Grant/Contract )
U01HL119242-01 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Alan Tita, University of Alabama at Birmingham
Study Sponsor  ICMJE University of Alabama at Birmingham
Collaborators  ICMJE
  • Columbia University
  • Drexel University College of Medicine
  • Rutgers, The State University of New Jersey
  • Lehigh Valley Hospital
  • Saint Peters University Hospital
  • Christiana Care Health Services
  • Washington University School of Medicine
  • Duke University
  • University of Texas Southwestern Medical Center
  • The University of Texas Health Science Center, Houston
  • Stanford University
  • University of Pennsylvania
  • The University of Texas Medical Branch, Galveston
  • University of Utah
  • Intermountain Health Care, Inc.
  • University of California, San Francisco
  • Johns Hopkins University
  • University of Pittsburgh
  • Ochsner Health System
  • University of North Carolina, Chapel Hill
  • National Heart, Lung, and Blood Institute (NHLBI)
  • WakeMed Health and Hospitals
  • San Francisco General Hospital
  • McKay-Dee Hospital
  • Winthrop University Hospital
  • New York Hospital Queens
  • Latter Day Saints Hospital
  • Lyndon B Johnson General Hospital
  • Virtua Medical Group
  • Bayview Medical Center
  • Duke Regional Hospital
  • Utah Valley Regional Medical Center
  • Northwestern
  • Brown (WIHRI)
  • Baylor College of Medicine
  • Case Western/Metro Health
  • Ohio State University
  • University of Iowa
  • University of California, San Diego
  • Indiana University
  • Unity Point Health-Meriter Hospital WI
  • Weill Medical College of Cornell University
  • University of Oklahoma
  • Medical University of South Carolina
  • Beaumont Hospital
  • University of Colorado, Denver
  • University of Kansas Medical Center
  • Denver Health and Hospital Authority
  • Gundersen Health System
  • Aurora Health Care
  • Oregon Health and Science University
  • Medical College of Wisconsin
  • Temple University
  • New Jersey Medical School
  • University of South Alabama
  • Vanderbilt University
  • University of Arkansas
  • Miami Valley Hospital
  • Emory University
  • St. Luke's Hospital and Health Network, Pennsylvania
  • Cleveland Clinic Fairview Hospital
  • University of Tennessee Health Science Center
  • TriHealth Inc.
  • Cleveland Clinic Hillcrest Hospital
  • Tulane University
  • Yale University
  • Arrowhead Regional Medical Center
  • Geisinger Clinic
Investigators  ICMJE
Principal Investigator: Alan Tita, MD, PhD University of Alabama at Birmingham - Clinical Coordinating Center
Principal Investigator: Gary Cutter, PhD University of Alabama at Birmingham-Data Coordinating Center
PRS Account University of Alabama at Birmingham
Verification Date November 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP