HypertensionPhase 4CHAPNCT02299414
Chronic Hypertension and Pregnancy (CHAP) Project
A Phase 4 study testing Anti-hypertensive therapy and No anti-hypertensive therapy (unless BP is severe) in people with Hypertension, run by University of Alabama at Birmingham at 72 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 12 years and older, women only
- Conditions the study is for
- Hypertension
- What is being tested?
- Anti-hypertensive therapy and No anti-hypertensive therapy (unless BP is severe)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2,408 participants
- Where
- 72 sitesUnited States
- Study dates
- Jun 2015to 16 Dec 2022
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 years and older
- Women only
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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);
- Singleton; and
- viable pregnancy <23 weeks of gestation.
Who cannot join
- Blood pressures prior to randomization ≥160 systolic or ≥105 diastolic (with or without treatment);
- Severe hypertension including patients currently treated with >1 antihypertensive medication (more likely to have severe chronic hypertension);
- Multi-fetal pregnancy;
- Known secondary cause of chronic hypertension;
- High-risk co-morbidities for which treatment may be indicated:
- Diabetes mellitus diagnosed at age ≤10 years or duration of diagnosis ≥20 years
Show all 23Show fewer
- 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
- Known major fetal anomaly;
- Known fetal demise;
- Suspected IUGR;
- Membrane rupture or planned termination prior to randomization;
- 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;
- Contraindication to labetalol and nifedipine (e.g. know hypersensitivity);
- Current substance abuse or addiction (cocaine, methamphetamine)
- Participation in another trial without prior approval (CHAP participants will not be enrolled in other trials without prior approval by protocol committee)
- Physician or provider refusal
- Patient refusal *The minimum age varies by center
Trial locations and contacts
72 sites in 1 country.
72 sites in 1 country
United States72 sites
Lehigh Valley Hospital/Health Network
Allentown, Pennsylvania, 18101
Emory University
Atlanta, Georgia, 30322
St. Luke's University Health Network
Bethlehem, Pennsylvania, 18015
University of Alabama at Birmingham, Clinical Coordinating Center
Birmingham, Alabama, 35294
University of Alabama at Birmingham, Data Coordinating Center
Birmingham, Alabama, 35294
Indiana University
Bloomington, Indiana, 47405
University of Colorado
Boulder, Colorado, 80204
University of North Carolina
Chapel Hill, North Carolina, 27599
Medical University of South Carolina
Charleston, South Carolina, 29425
TriHealth, Inc
Cincinnati, Ohio, 45220
Case Western/Metro Health
Cleveland, Ohio, 44109
Cleveland Clinic Fairview
Cleveland, Ohio, 44111
Arrowhead Regional Medical Center
Colton, California, 92324
Ohio State University
Columbus, Ohio, 43210
UT Southwestern
Dallas, Texas, 75390
Geisinger Clinic
Danville, Pennsylvania, 17822
Miami Valley Hospital
Dayton, Ohio, 45409
Denver Health
Denver, Colorado, 80204
Duke Regional Medical Center
Durham, North Carolina, 27704
Duke University
Durham, North Carolina, 27705
Northwestern
Evanston, Illinois, 60208
New York Presbyterian Queens
Flushing, New York, 11355
UT Medical Branch
Galveston, Texas, 77555
Baylor College of Medicine
Houston, Texas, 77030
UT Houston
Houston, Texas, 77030
University of Iowa
Iowa City, Iowa, 52242
University of Mississippi Medical College
Jackson, Mississippi, 39216
Gundersen Health System
La Crosse, Wisconsin, 54601
University of Kansas Medical Center
Lawrence, Kansas, 66045
University of Kentucky
Lexington, Kentucky, 40536
University of Arkansas for Medical Sciences
Little Rock, Arkansas, 72205
Unity Point Health-Meriter Hospital
Madison, Wisconsin, 53715
Marshfield Clinic
Marshfield, Wisconsin, 54449
Cleveland Clinic-Hillcrest Hospital
Mayfield Heights, Ohio, 44124
University of Tennessee Health Science Center
Memphis, Tennessee, 38103
Medical College of Wisconsin
Milwaukee, Wisconsin, 53226
Aurora Research Institute
Milwaukee, Wisconsin, 53233
Winthrop University Hospital
Mineola, New York, 11501
University of South Alabama
Mobile, Alabama, 36604
Vanderbilt University
Nashville, Tennessee, 37232
Robert Wood Johnson Medical School
New Brunswick, New Jersey, 08901
St. Peters University Hospital
New Brunswick, New Jersey, 08901
Yale University
New Haven, Connecticut, 06511
Tulane
New Orleans, Louisiana, 70112
Ochsner Health System/Medical Center
New Orleans, Louisiana, 70115
Columbia University
New York, New York, 10032
Weill Cornell
New York, New York, 10065
Christiana Care Health Services
Newark, Delaware, 19713
New Jersey Medical School
Newark, New Jersey, 07103
McKay Dee Hospital
Ogden, Utah, 84403
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, 73104
Drexel University College of Medicine
Philadelphia, Pennsylvania, 19019
Hospital of the University of Pennsylvania
Philadelphia, Pennsylvania, 19104
Pennsylvania Hospital
Philadelphia, Pennsylvania, 19104
University of Pennsylvania
Philadelphia, Pennsylvania, 19104
Temple University
Philadelphia, Pennsylvania, 19140
University of Pittsburg/Magee Women's Center
Pittsburgh, Pennsylvania, 15201
Oregon Health & Science University
Portland, Oregon, 97239
Brown (WIHRI)
Providence, Rhode Island, 02912
Utah Valley Regional Medical Center
Provo, Utah, 84604
WakeMed
Raleigh, North Carolina, 27610
Beaumont Hospital
Royal Oak, Michigan, 48073
Intermountain Healthcare
Salt Lake City, Utah, 84132
University of Utah
Salt Lake City, Utah, 84132
LDS Hospital
Salt Lake City, Utah, 84143
University of California, San Diego
San Diego, California, 92110
General Hospital of San Francisco
San Francisco, California, 94110
University of California San Francisco
San Francisco, California, 94143
Virtua Medical Group
Sewell, New Jersey, 08080
Washington University
St Louis, Missouri, 63110
Stanford University
Stanford, California, 94305
University of South Florida
Tampa, Florida, 33606
About this study
Official title: A Pragmatic Multicenter Randomized Clinical Trial (RCT) of Antihypertensive Therapy for Mild Chronic Hypertension During Pregnancy: Chronic Hypertension and Pregnancy (CHAP) Project
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.
Read the 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.
- Conditions
- Hypertension
- Being tested
- Anti-hypertensive therapy, No anti-hypertensive therapy (unless BP is severe)
- Keywords
- Pregnancy, Chronic hypertension
- Medical subject headings
- Hypertension
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Anti-hypertensive therapyDrug
Also called Normodyne, Trandate, Procardia XL, Adalat
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 therapy (unless BP is severe)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.
| Study group | Role | What they receive |
|---|---|---|
| Anti-hypertensive therapy to goal <140/90 mmHg | Experimental | 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 Receives: Drug: Anti-hypertensive therapy |
| No anti-hypertensive unless BP is severe (≥160/105 mmHg | Active comparator | 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 Receives: Other: No anti-hypertensive therapy (unless BP is severe) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Composite Adverse Perinatal Outcome
One or more severe outcomes including fetal death or neonatal death up to discharge or 90 days if prior; preeclampsia with severe features up to 2 weeks postpartum (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).
Measured: Up to 2 weeks postpartum for preeclampsia or 90 days for neonatal death
Small for Gestational Age (Safety)
Birth weight less than 10th percentile for gestational age at birth according to accepted national standard
Measured: Until delivery
Secondary outcomes (5)
Composite of Maternal Death or Severe Cardiovascular Morbidity
One or more of maternal death, new heart failure, stroke, encephalopathy, angina, myocardial infarction or ischemia, pulmonary edema, ICU admission/intubation, or renal failure
Measured: Up to 6 weeks (4-12 weeks) after delivery
Severe Maternal Hypertension + Components of the Primary Composite Endpoint
Persistent severe hypertension with or without proteinuria + the primary composite
Measured: Up to 2 weeks postpartum or 90 days for neonatal death
Preterm Birth and Indicated Preterm Birth (<37 Weeks)
Preterm birth and Indicated preterm birth (<37 weeks) includes any preterm birth less than 37 weeks
Measured: Until delivery
Composite of Severe Neonatal Morbidities
One or more of Bronchopulmonary dysplasia (BPD), Retinopathy of prematurity (ROP), Necrotizing enterocolitis (NEC), Intraventricular hemorrhage (VH) grade III/IV
Measured: Up to 90 days post delivery
Adherence to Treatment After Delivery
Counts with high adherence to antihypertensive therapy after delivery for those prescribed medications.
Measured: 6 weeks (4-12 weeks) after delivery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Nov 2014 (estimated)
- Study startJun 2015
- Primary completion1 Apr 2022
- Study completion16 Dec 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for HypertensionStudies of the same condition, open and under way.
- More trials run by University of Alabama at BirminghamThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 2,408 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Alabama at Birmingham
- Sponsor type
- University, hospital or other
- 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, Duke Regional Hospital, Utah Valley Regional Medical Center, Northwestern University, Women and Infants Hospital of Rhode Island, Baylor College of Medicine, Case Western/Metro Health, Ohio State University, University of Iowa, University of California, San Diego, Indiana University, Meriter Foundation, 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, Wake Forest University Health Sciences, Oregon Health and Science University, Medical College of Wisconsin, Temple University, New Jersey Medical School, University of South Alabama, Vanderbilt University, University of Arkansas, Emory University, St. Luke's Hospital and Health Network, Pennsylvania, The Cleveland Clinic, University of Tennessee, TriHealth Inc., Tulane University, Yale University, Arrowhead Regional Medical Center, Geisinger Clinic, Miami Valley Hospital
- Responsible party
- Principal investigator, Alan Tita, University of Alabama at Birmingham
- Investigators
- Alan Tita, MD, PhD, Principal investigator, University of Alabama at Birmingham - Clinical Coordinating CenterGary Cutter, PhD, Principal investigator, University of Alabama at Birmingham-Data Coordinating CenterJeff Szychowski, PhD, Principal investigator, University of Alabama at Birmingham-Data Coordinating Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02299414
- Sponsor's protocol ID
- 1U01HL119242-01
- Other IDs
- U01HL119242-01
- Acronym
- CHAP
- Status last verified
- May 2023
- First submitted
- 28 Oct 2014
- Last updated
- 17 May 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 38949541Moore 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.
PubMed 38781591Bailey 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.
PubMed 37769314Goulding 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.
PubMed 37437694Tita 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.
PubMed 35363951
Study at a glance
From the registry record, last updated by the sponsor on 17 May 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pragmatic Multicenter Randomized Clinical Trial (RCT) of Antihypertensive Therapy for Mild Chronic Hypertension During Pregnancy: Chronic Hypertension and Pregnancy (CHAP) Project
- ClinicalTrials.gov ID
- NCT02299414
- Acronym / sponsor ID
- CHAP / 1U01HL119242-01
- Conditions
- Hypertension
- Keywords
- Pregnancy, Chronic hypertension
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 2,408 participants (actual)
- Lead sponsor
- University of Alabama at BirminghamUniversity, hospital or other
- 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, Duke Regional Hospital, Utah Valley Regional Medical Center, Northwestern University, Women and Infants Hospital of Rhode Island, Baylor College of Medicine, Case Western/Metro Health, Ohio State University, University of Iowa, University of California, San Diego, Indiana University, Meriter Foundation, 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, Wake Forest University Health Sciences, Oregon Health and Science University, Medical College of Wisconsin, Temple University, New Jersey Medical School, University of South Alabama, Vanderbilt University, University of Arkansas, Emory University, St. Luke's Hospital and Health Network, Pennsylvania, The Cleveland Clinic, University of Tennessee, TriHealth Inc., Tulane University, Yale University, Arrowhead Regional Medical Center, Geisinger Clinic, Miami Valley Hospital
- Study start
- Jun 2015 (actual)
- Primary completion
- 1 Apr 2022 (actual)
- Study completion
- 16 Dec 2022 (actual)
- First posted
- 24 Nov 2014 (estimated)
- Results
- Posted 17 May 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Anti-hypertensive therapy to goal <140/90 mmHg | Experimental | Drug: Anti-hypertensive therapyLabetalol 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 |
| No anti-hypertensive unless BP is severe (≥160/105 mmHg | Active comparator | Other: No anti-hypertensive therapy (unless BP is severe)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 |
Who may qualify
- Ages
- 12 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (3 listed)
- 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);
- Singleton; and
- viable pregnancy <23 weeks of gestation.
Key exclusion criteria (23 listed)
- Blood pressures prior to randomization ≥160 systolic or ≥105 diastolic (with or without treatment);
- Severe hypertension including patients currently treated with >1 antihypertensive medication (more likely to have severe chronic hypertension);
- Multi-fetal pregnancy;
- Known secondary cause of chronic hypertension;
- High-risk co-morbidities for which treatment may be indicated:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Anti-hypertensive therapyAlso: Normodyne, Trandate, Procardia XL, Adalat1st line anti-hypertensive (Labetalol or Nifedipine ER) started; escalate to maximum dose and a preferred 2nd line medication if needed (nifedipine ER or Labetalol) | Drug | Anti-hypertensive therapy to goal <140/90 mmHg |
| 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. | Other | No anti-hypertensive unless BP is severe (≥160/105 mmHg |
Primary outcome
Composite Adverse Perinatal Outcome
Time frame: Up to 2 weeks postpartum for preeclampsia or 90 days for neonatal death
One or more severe outcomes including fetal death or neonatal death up to discharge or 90 days if prior; preeclampsia with severe features up to 2 weeks postpartum (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 (Safety)
Time frame: Until delivery
Birth weight less than 10th percentile for gestational age at birth according to accepted national standard
5 secondary outcomes
Composite of Maternal Death or Severe Cardiovascular Morbidity
Time frame: Up to 6 weeks (4-12 weeks) after delivery
Severe Maternal Hypertension + Components of the Primary Composite Endpoint
Time frame: Up to 2 weeks postpartum or 90 days for neonatal death
Preterm Birth and Indicated Preterm Birth (<37 Weeks)
Time frame: Until delivery
Composite of Severe Neonatal Morbidities
Time frame: Up to 90 days post delivery
Adherence to Treatment After Delivery
Time frame: 6 weeks (4-12 weeks) after delivery
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 May 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 38949541Sanusi 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.
- Derived from this study: PubMed 38781591Moore 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.
- Derived from this study: PubMed 37769314Bailey 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.
- Derived from this study: PubMed 37437694Goulding 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.
- Derived from this study: PubMed 35363951Tita 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Alan Tita, MD, PhD principal investigator
University of Alabama at Birmingham - Clinical Coordinating Center
Gary Cutter, PhD principal investigator
University of Alabama at Birmingham-Data Coordinating Center
Jeff Szychowski, PhD principal investigator
University of Alabama at Birmingham-Data Coordinating Center
72 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Anti-hypertensive therapy and No anti-hypertensive therapy (unless BP is severe) in people with Hypertension, run by University of Alabama at Birmingham at 72 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 17 May 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 72 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 17 May 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Composite Adverse Perinatal Outcome (time frame: Up to 2 weeks postpartum for preeclampsia or 90 days for neonatal death). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02299414, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 May 2023.