Chronic Hypertension and Pregnancy (CHAP) Project

NCT ID: NCT02299414

Last Updated: 2023-05-17

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

View full results

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

PHASE4

Total Enrollment

2408 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-06-30

Study Completion Date

2022-12-16

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

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.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Hypertension

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

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

Group Type EXPERIMENTAL

Anti-hypertensive therapy

Intervention Type DRUG

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)

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

Group Type ACTIVE_COMPARATOR

No anti-hypertensive therapy (unless BP is severe)

Intervention Type OTHER

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.

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

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)

Intervention Type DRUG

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.

Intervention Type OTHER

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

Normodyne Trandate Procardia XL Adalat

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

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. Severe hypertension including 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:

* Diabetes mellitus diagnosed at age ≤10 years or duration of diagnosis ≥20 years
* Diabetes mellitus complicated by end organ damage (retinopathy, nephropathy, heart disease, transplant)
* Chronic kidney disease - including baseline proteinuria (\>300mg/24-hr, protein/creatinine 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. If a p/c ratio is \>0.3, the patient may be included if a 24-hour urine is \< 300 mg.
* 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 and nifedipine (e.g. know hypersensitivity);
12. Current substance abuse or addiction (cocaine, methamphetamine)
13. Participation in another trial without prior approval (CHAP participants will not be enrolled in other trials without prior approval by protocol committee)
14. Physician or provider refusal
15. Patient refusal \*The minimum age varies by center
Minimum Eligible Age

12 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

Columbia University

OTHER

Sponsor Role collaborator

Drexel University College of Medicine

OTHER

Sponsor Role collaborator

Rutgers, The State University of New Jersey

OTHER

Sponsor Role collaborator

Lehigh Valley Hospital

OTHER

Sponsor Role collaborator

Saint Peters University Hospital

OTHER

Sponsor Role collaborator

Christiana Care Health Services

OTHER

Sponsor Role collaborator

Washington University School of Medicine

OTHER

Sponsor Role collaborator

Duke University

OTHER

Sponsor Role collaborator

University of Texas Southwestern Medical Center

OTHER

Sponsor Role collaborator

The University of Texas Health Science Center, Houston

OTHER

Sponsor Role collaborator

Stanford University

OTHER

Sponsor Role collaborator

University of Pennsylvania

OTHER

Sponsor Role collaborator

The University of Texas Medical Branch, Galveston

OTHER

Sponsor Role collaborator

University of Utah

OTHER

Sponsor Role collaborator

Intermountain Health Care, Inc.

OTHER

Sponsor Role collaborator

University of California, San Francisco

OTHER

Sponsor Role collaborator

Johns Hopkins University

OTHER

Sponsor Role collaborator

University of Pittsburgh

OTHER

Sponsor Role collaborator

Ochsner Health System

OTHER

Sponsor Role collaborator

University of North Carolina, Chapel Hill

OTHER

Sponsor Role collaborator

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role collaborator

WakeMed Health and Hospitals

OTHER

Sponsor Role collaborator

San Francisco General Hospital

OTHER

Sponsor Role collaborator

McKay-Dee Hospital

OTHER

Sponsor Role collaborator

Winthrop University Hospital

OTHER

Sponsor Role collaborator

New York Hospital Queens

OTHER

Sponsor Role collaborator

Latter Day Saints Hospital

OTHER

Sponsor Role collaborator

Lyndon B Johnson General Hospital

OTHER

Sponsor Role collaborator

Virtua Medical Group

OTHER

Sponsor Role collaborator

Duke Regional Hospital

OTHER

Sponsor Role collaborator

Utah Valley Regional Medical Center

OTHER

Sponsor Role collaborator

Northwestern University

OTHER

Sponsor Role collaborator

Women and Infants Hospital of Rhode Island

OTHER

Sponsor Role collaborator

Baylor College of Medicine

OTHER

Sponsor Role collaborator

Case Western/Metro Health

UNKNOWN

Sponsor Role collaborator

Ohio State University

OTHER

Sponsor Role collaborator

University of Iowa

OTHER

Sponsor Role collaborator

University of California, San Diego

OTHER

Sponsor Role collaborator

Indiana University

OTHER

Sponsor Role collaborator

Meriter Foundation

OTHER

Sponsor Role collaborator

Weill Medical College of Cornell University

OTHER

Sponsor Role collaborator

University of Oklahoma

OTHER

Sponsor Role collaborator

Medical University of South Carolina

OTHER

Sponsor Role collaborator

Beaumont Hospital

OTHER

Sponsor Role collaborator

University of Colorado, Denver

OTHER

Sponsor Role collaborator

University of Kansas Medical Center

OTHER

Sponsor Role collaborator

Denver Health and Hospital Authority

OTHER

Sponsor Role collaborator

Gundersen Health System

OTHER

Sponsor Role collaborator

Wake Forest University Health Sciences

OTHER

Sponsor Role collaborator

Oregon Health and Science University

OTHER

Sponsor Role collaborator

Medical College of Wisconsin

OTHER

Sponsor Role collaborator

Temple University

OTHER

Sponsor Role collaborator

New Jersey Medical School

OTHER

Sponsor Role collaborator

University of South Alabama

OTHER

Sponsor Role collaborator

Vanderbilt University

OTHER

Sponsor Role collaborator

University of Arkansas

OTHER

Sponsor Role collaborator

Emory University

OTHER

Sponsor Role collaborator

St. Luke's Hospital and Health Network, Pennsylvania

OTHER

Sponsor Role collaborator

The Cleveland Clinic

OTHER

Sponsor Role collaborator

University of Tennessee

OTHER

Sponsor Role collaborator

TriHealth Inc.

OTHER

Sponsor Role collaborator

Tulane University

OTHER

Sponsor Role collaborator

Yale University

OTHER

Sponsor Role collaborator

Arrowhead Regional Medical Center

OTHER

Sponsor Role collaborator

Geisinger Clinic

OTHER

Sponsor Role collaborator

Miami Valley Hospital

OTHER

Sponsor Role collaborator

University of Alabama at Birmingham

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Alan Tita

Principal Investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Alan Tita, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Alabama at Birmingham - Clinical Coordinating Center

Gary Cutter, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Alabama at Birmingham-Data Coordinating Center

Jeff Szychowski, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Alabama at Birmingham-Data Coordinating Center

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

University of Alabama at Birmingham, Clinical Coordinating Center

Birmingham, Alabama, United States

Site Status

University of Alabama at Birmingham, Data Coordinating Center

Birmingham, Alabama, United States

Site Status

University of South Alabama

Mobile, Alabama, United States

Site Status

University of Arkansas for Medical Sciences

Little Rock, Arkansas, United States

Site Status

Arrowhead Regional Medical Center

Colton, California, United States

Site Status

University of California, San Diego

San Diego, California, United States

Site Status

General Hospital of San Francisco

San Francisco, California, United States

Site Status

University of California San Francisco

San Francisco, California, United States

Site Status

Stanford University

Stanford, California, United States

Site Status

University of Colorado

Boulder, Colorado, United States

Site Status

Denver Health

Denver, Colorado, United States

Site Status

Yale University

New Haven, Connecticut, United States

Site Status

Christiana Care Health Services

Newark, Delaware, United States

Site Status

University of South Florida

Tampa, Florida, United States

Site Status

Emory University

Atlanta, Georgia, United States

Site Status

Northwestern

Evanston, Illinois, United States

Site Status

Indiana University

Bloomington, Indiana, United States

Site Status

University of Iowa

Iowa City, Iowa, United States

Site Status

University of Kansas Medical Center

Lawrence, Kansas, United States

Site Status

University of Kentucky

Lexington, Kentucky, United States

Site Status

Tulane

New Orleans, Louisiana, United States

Site Status

Ochsner Health System/Medical Center

New Orleans, Louisiana, United States

Site Status

Beaumont Hospital

Royal Oak, Michigan, United States

Site Status

University of Mississippi Medical College

Jackson, Mississippi, United States

Site Status

Washington University

St Louis, Missouri, United States

Site Status

Robert Wood Johnson Medical School

New Brunswick, New Jersey, United States

Site Status

St. Peters University Hospital

New Brunswick, New Jersey, United States

Site Status

New Jersey Medical School

Newark, New Jersey, United States

Site Status

Virtua Medical Group

Sewell, New Jersey, United States

Site Status

New York Presbyterian Queens

Flushing, New York, United States

Site Status

Winthrop University Hospital

Mineola, New York, United States

Site Status

Columbia University

New York, New York, United States

Site Status

Weill Cornell

New York, New York, United States

Site Status

University of North Carolina

Chapel Hill, North Carolina, United States

Site Status

Duke Regional Medical Center

Durham, North Carolina, United States

Site Status

Duke University

Durham, North Carolina, United States

Site Status

WakeMed

Raleigh, North Carolina, United States

Site Status

TriHealth, Inc

Cincinnati, Ohio, United States

Site Status

Case Western/Metro Health

Cleveland, Ohio, United States

Site Status

Cleveland Clinic Fairview

Cleveland, Ohio, United States

Site Status

Ohio State University

Columbus, Ohio, United States

Site Status

Miami Valley Hospital

Dayton, Ohio, United States

Site Status

Cleveland Clinic-Hillcrest Hospital

Mayfield Heights, Ohio, United States

Site Status

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, United States

Site Status

Oregon Health & Science University

Portland, Oregon, United States

Site Status

Lehigh Valley Hospital/Health Network

Allentown, Pennsylvania, United States

Site Status

St. Luke's University Health Network

Bethlehem, Pennsylvania, United States

Site Status

Geisinger Clinic

Danville, Pennsylvania, United States

Site Status

Drexel University College of Medicine

Philadelphia, Pennsylvania, United States

Site Status

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, United States

Site Status

Pennsylvania Hospital

Philadelphia, Pennsylvania, United States

Site Status

University of Pennsylvania

Philadelphia, Pennsylvania, United States

Site Status

Temple University

Philadelphia, Pennsylvania, United States

Site Status

University of Pittsburg/Magee Women's Center

Pittsburgh, Pennsylvania, United States

Site Status

Brown (WIHRI)

Providence, Rhode Island, United States

Site Status

Medical University of South Carolina

Charleston, South Carolina, United States

Site Status

University of Tennessee Health Science Center

Memphis, Tennessee, United States

Site Status

Vanderbilt University

Nashville, Tennessee, United States

Site Status

UT Southwestern

Dallas, Texas, United States

Site Status

UT Medical Branch

Galveston, Texas, United States

Site Status

Baylor College of Medicine

Houston, Texas, United States

Site Status

UT Houston

Houston, Texas, United States

Site Status

McKay Dee Hospital

Ogden, Utah, United States

Site Status

Utah Valley Regional Medical Center

Provo, Utah, United States

Site Status

Intermountain Healthcare

Salt Lake City, Utah, United States

Site Status

University of Utah

Salt Lake City, Utah, United States

Site Status

LDS Hospital

Salt Lake City, Utah, United States

Site Status

Gundersen Health System

La Crosse, Wisconsin, United States

Site Status

Unity Point Health-Meriter Hospital

Madison, Wisconsin, United States

Site Status

Marshfield Clinic

Marshfield, Wisconsin, United States

Site Status

Medical College of Wisconsin

Milwaukee, Wisconsin, United States

Site Status

Aurora Research Institute

Milwaukee, Wisconsin, United States

Site Status

Countries

Review the countries where the study has at least one active or historical site.

United States

References

Explore related publications, articles, or registry entries linked to this study.

Sanusi AA, Leach J, Boggess K, Dugoff L, Sibai B, Lawrence K, Hughes BL, Bell J, Aagaard K, Edwards RK, Gibson KS, Haas DM, Plante L, Metz TD, Casey B, Esplin S, Longo S, Hoffman MK, Saade GR, Hoppe KK, Foroutan J, Tuuli M, Owens MY, Simhan HN, Frey H, Rosen T, Palatnik A, Baker S, August P, Reddy UM, Su EJ, Krishna I, Nguyen NA, Norton ME, Skupski D, El-Sayed YY, Ogunyemi D, Galis ZS, Harper L, Ambalavanan N, Geller NL, Kuo HC, Sinkey RG, Librizzi R, Pereira L, Magann EF, Habli M, Williams S, Mari G, Pridjian G, McKenna DS, Parrish M, Eugene Chang, Osmundson S, Quinones J, Szychowski JM, Tita ATN. Pregnancy Outcomes of Nifedipine Compared With Labetalol for Oral Treatment of Mild Chronic Hypertension. Obstet Gynecol. 2024 Jul 1;144(1):126-134. doi: 10.1097/AOG.0000000000005613. Epub 2024 May 23.

Reference Type DERIVED
PMID: 38949541 (View on PubMed)

Moore MD, Kuo HC, Sinkey RG, Boggess K, Dugoff L, Sibai B, Lawrence K, Hughes BL, Bell J, Aagaard K, Edwards RK, Gibson KS, Haas DM, Plante L, Metz TD, Casey B, Esplin S, Longo S, Hoffman MK, Saade GR, Hoppe KK, Foroutan J, Tuuli M, Owens MY, Simhan HN, Frey HA, Rosen T, Palatnik A, Baker S, August P, Reddy UM, Kinzler W, Su EJ, Krishna I, Nguyen NA, Norton ME, Skupski D, El-Sayed YY, Ogunyemi D, Librizzi R, Pereira L, Magann EF, Habli M, Williams S, Mari G, Pridjian G, McKenna DS, Parrish M, Chang E, Osmundson S, Quinones JN, Leach J, Sanusi A, Galis ZS, Harper L, Ambalavanan N, Szychowski JM, Tita ATN. Mean Arterial Pressure and Neonatal Outcomes in Pregnancies Complicated by Mild Chronic Hypertension. Obstet Gynecol. 2024 Jul 1;144(1):101-108. doi: 10.1097/AOG.0000000000005611. Epub 2024 May 23.

Reference Type DERIVED
PMID: 38781591 (View on PubMed)

Bailey EJ, Tita ATN, Leach J, Boggess K, Dugoff L, Sibai B, Lawrence K, Hughes BL, Bell J, Aagaard K, Edwards RK, Gibson K, Haas DM, Plante L, Metz TD, Casey BM, Esplin S, Longo S, Hoffman M, Saade GR, Foroutan J, Tuuli MG, Owens MY, Simhan HN, Frey HA, Rosen T, Palatnik A, Baker S, August P, Reddy UM, Kinzler W, Su EJ, Krishna I, Nguyen N, Norton ME, Skupski D, El-Sayed YY, Ogunyemi D, Galis ZS, Harper L, Ambalavanan N, Oparil S, Kuo HC, Szychowski JM, Hoppe K. Perinatal Outcomes Associated With Management of Stage 1 Hypertension. Obstet Gynecol. 2023 Dec 1;142(6):1395-1404. doi: 10.1097/AOG.0000000000005410. Epub 2023 Sep 28.

Reference Type DERIVED
PMID: 37769314 (View on PubMed)

Goulding AN, Antoniewicz L, Leach JM, Boggess K, Dugoff L, Sibai B, Lawrence K, Hughes BL, Bell J, Edwards RK, Gibson K, Haas DM, Plante L, Metz TD, Casey B, Esplin S, Longo S, Hoffman M, Saade GR, Hoppe KK, Foroutan J, Tuuli M, Owens MY, Simhan HN, Frey H, Rosen T, Palatnik A, Baker S, Reddy UM, Kinzler W, Su E, Krishna I, Nguyen N, Norton ME, Skupski D, El-Sayed YY, Ogunyemi D, Harper LM, Ambalavanan N, Oparil S, Szychowski JM, Tita AT; Chronic Hypertension and Pregnancy Trial Consortium. Breastfeeding initiation and duration among people with mild chronic hypertension: a secondary analysis of the Chronic Hypertension and Pregnancy trial. Am J Obstet Gynecol MFM. 2023 Sep;5(9):101086. doi: 10.1016/j.ajogmf.2023.101086. Epub 2023 Jul 10.

Reference Type DERIVED
PMID: 37437694 (View on PubMed)

Tita AT, Szychowski JM, Boggess K, Dugoff L, Sibai B, Lawrence K, Hughes BL, Bell J, Aagaard K, Edwards RK, Gibson K, Haas DM, Plante L, Metz T, Casey B, Esplin S, Longo S, Hoffman M, Saade GR, Hoppe KK, Foroutan J, Tuuli M, Owens MY, Simhan HN, Frey H, Rosen T, Palatnik A, Baker S, August P, Reddy UM, Kinzler W, Su E, Krishna I, Nguyen N, Norton ME, Skupski D, El-Sayed YY, Ogunyemi D, Galis ZS, Harper L, Ambalavanan N, Geller NL, Oparil S, Cutter GR, Andrews WW; Chronic Hypertension and Pregnancy (CHAP) Trial Consortium. Treatment for Mild Chronic Hypertension during Pregnancy. N Engl J Med. 2022 May 12;386(19):1781-1792. doi: 10.1056/NEJMoa2201295. Epub 2022 Apr 2.

Reference Type DERIVED
PMID: 35363951 (View on PubMed)

Provided Documents

Download supplemental materials such as informed consent forms, study protocols, or participant manuals.

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

U01HL119242-01

Identifier Type: NIH

Identifier Source: secondary_id

View Link

1U01HL119242-01

Identifier Type: NIH

Identifier Source: org_study_id

View Link

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.

Acute Control of Chronic Hypertension
NCT03877692 TERMINATED PHASE4