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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

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.

Condition or disease Intervention/treatment Phase
Hypertension Drug: Anti-hypertensive therapy Other: No anti-hypertensive therapy (unless BP is severe) Phase 4

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 2404 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Pragmatic Multicenter Randomized Clinical Trial (RCT) of Antihypertensive Therapy for Mild Chronic Hypertension During Pregnancy: Chronic Hypertension and Pregnancy (CHAP) Project
Study Start Date : June 2015
Estimated Primary Completion Date : June 2021
Estimated Study Completion Date : June 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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
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

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
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.




Primary Outcome Measures :
  1. 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).

  2. Small for Gestational Age [ Time Frame: Until delivery ]
    Birth weight less than 10th percentile for gestational age at birth according to accepted national standard


Secondary Outcome Measures :
  1. 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

  2. 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

  3. Adherence to treatment after delivery [ Time Frame: Up to 6 weeks (4-12 weeks) after delivery ]
    Adherence to antihypertensive therapy after delivery


Other Outcome Measures:
  1. Preeclampsia [ Time Frame: Up to 2 weeks after delivery ]
    Mild or severe, including eclampsia

  2. 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

  3. Severe hypertension [ Time Frame: Up to 6 weeks (4-12 weeks) after delivery ]
    Blood pressure ≥160/110

  4. Cesarean delivery [ Time Frame: Until delivery ]
    Cesarean delivery

  5. Preterm birth [ Time Frame: At birth ]
    Delivery at <37 weeks

  6. NICU admission [ Time Frame: Up to 6 weeks (4-12 weeks) after delivery ]
    NICU admission and length of NICU stay

  7. Low birth weight [ Time Frame: At birth ]
    Birth weight <2500g

  8. Ponderal index [ Time Frame: At birth ]
    Mean ponderal index

  9. Head circumference [ Time Frame: At birth ]
    Mean head circumference

  10. Placental weight [ Time Frame: At delivery ]
    Mean placental weight

  11. Hypoglycemia [ Time Frame: From delivery to hospital discharge (2 - 3 days after delivery) ]
    Prevalence of hypoglycemia

  12. Bradycardia [ Time Frame: From delivery to hospital discharge (2 - 3 days after delivery) ]
    Prevalence of bradycardia

  13. Hypotension [ Time Frame: From delivery to hospital discharge (2 - 3 days after delivery) ]
    Incidence (%) with hypotension

  14. Respiratory distress syndrome (RDS) [ Time Frame: From delivery to hospital discharge (2 - 3 days after delivery) ]
    Incidence (%) with RDS

  15. Bronchopulmonary dysplasia (BPD) [ Time Frame: Up to 3 months after delivery ]
    Incidence (%) with BPD

  16. Intubation/ventilation [ Time Frame: From delivery to hospital discharge (2 - 3 days after delivery) ]
    Incidence (%) with intubation for ventilation

  17. 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

  18. Necrotizing enterocolitis (NEC) [ Time Frame: Up to 3 months after delivery ]
    Incidence (%) with NEC

  19. Hyperbilirubinemia [ Time Frame: From delivery to hospital discharge (2 - 3 days after delivery) ]
    Incidence (%) with hyperbilirubinemia

  20. 5-min Apgar score [ Time Frame: At delivery ]
    Apgar score <7

  21. Sepsis [ Time Frame: From delivery to hospital discharge (2 - 3 days after delivery) ]
    Incidence (%) with sepsis

  22. 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

  23. Hospitalizations [ Time Frame: Up to 3 months postpartum ]
    Number of hospitalizations before or after delivery

  24. Postpartum unscheduled or ER visits [ Time Frame: Up to 3 months after delivery ]
    Number of postpartum unscheduled or ER visits

  25. Postpartum hospitalizations [ Time Frame: Up to 3 months after delivery ]
    Number of postpartum hospitalizations



Information from the National Library of Medicine

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Ages Eligible for Study:   12 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02299414


Contacts
Layout table for location contacts
Contact: Alan Tita, MD, PhD 205-934-5612 atita@uabmc.edu
Contact: Michelle Feese, MPH 205-975-8633 mfeese@uab.edu

  Show 75 Study Locations
Sponsors and Collaborators
University of Alabama at Birmingham
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
Layout table for investigator information
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

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Responsible Party: Alan Tita, Principal Investigator, University of Alabama at Birmingham
ClinicalTrials.gov Identifier: NCT02299414     History of Changes
Other Study ID Numbers: 1U01HL119242-01 ( U.S. NIH Grant/Contract )
U01HL119242-01 ( U.S. NIH Grant/Contract )
First Posted: November 24, 2014    Key Record Dates
Last Update Posted: November 6, 2019
Last Verified: November 2019
Keywords provided by Alan Tita, University of Alabama at Birmingham:
Pregnancy
Chronic hypertension
Additional relevant MeSH terms:
Layout table for MeSH terms
Membrane Transport Modulators
Hypertension
Vascular Diseases
Cardiovascular Diseases
Labetalol
Nifedipine
Antihypertensive Agents
Calcium Channel Blockers
Molecular Mechanisms of Pharmacological Action
Calcium-Regulating Hormones and Agents
Physiological Effects of Drugs
Vasodilator Agents
Tocolytic Agents
Reproductive Control Agents
Adrenergic beta-Antagonists
Adrenergic Antagonists
Adrenergic Agents
Neurotransmitter Agents
Sympathomimetics
Autonomic Agents
Peripheral Nervous System Agents
Adrenergic alpha-1 Receptor Antagonists
Adrenergic alpha-Antagonists