Chronic Hypertension and Pregnancy (CHAP) Project

• Sponsor: University of Alabama at Birmingham (Other)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT02299414
• Collaborator: Columbia University (Other), Drexel University College of Medicine (Other), Rutgers, The State University of New Jersey (Other), Lehigh Valley Hospital (Other), Saint Peters University Hospital (Other), Christiana Care Health Services (Other), Washington University School of Medicine (Other), Duke University (Other), University of Texas Southwestern Medical Center (Other), The University of Texas Health Science Center, Houston (Other), Stanford University (Other), University of Pennsylvania (Other), The University of Texas Medical Branch, Galveston (Other), University of Utah (Other), Intermountain Health Care, Inc. (Other), University of California, San Francisco (Other), Johns Hopkins University (Other), University of Pittsburgh (Other), Ochsner Health System (Other), University of North Carolina, Chapel Hill (Other), National Heart, Lung, and Blood Institute (NHLBI) (NIH), WakeMed Health and Hospitals (Other), San Francisco General Hospital (Other), McKay-Dee Hospital (Other), Winthrop University Hospital (Other), New York Hospital Queens (Other), Latter Day Saints Hospital (Other), Lyndon B Johnson General Hospital (Other), Virtua Medical Group (Other), Bayview Medical Center (Other), Duke Regional Hospital (Other), Utah Valley Regional Medical Center (Other), Northwestern (Other), Brown (WIHRI) (Other), Baylor College of Medicine (Other), Case Western/Metro Health (Other), Ohio State University (Other), University of Iowa (Other), University of California, San Diego (Other), Indiana University (Other), Unity Point Health-Meriter Hospital WI (Other), Weill Medical College of Cornell University (Other), University of Oklahoma (Other), Medical University of South Carolina (Other), Beaumont Hospital (Other), University of Colorado, Denver (Other), University of Kansas Medical Center (Other), Denver Health and Hospital Authority (Other), Gundersen Health System (Other), Aurora Health Care (Other), Oregon Health and Science University (Other), Medical College of Wisconsin (Other), Temple University (Other), New Jersey Medical School (Other), University of South Alabama (Other), Vanderbilt University (Other), University of Arkansas (Other), Emory University (Other), St. Luke's Hospital and Health Network, Pennsylvania (Other), Cleveland Clinic Fairview Hospital (Other), University of Tennessee Health Science Center (Other), TriHealth Inc. (Other), Cleveland Clinic Hillcrest Hospital (Other), Tulane University (Other), Yale University (Other), Arrowhead Regional Medical Center (Other), Geisinger Clinic (Other), Premier Health Miami Valley Hospital (Other)
• Enrollment: 2,404
• Locations: 72
• Arms: 2
• Anticipated Duration (Months): 88
• Patients Per Site: 33.4
• Patients Per Site Per Month: 0.4

Study Details

Study Description

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.

Study Design

• Study Type: Interventional
• Anticipated 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
• Actual Study Start Date: Jun 1, 2015
• Actual Primary Completion Date: Apr 1, 2022
• Anticipated Study Completion Date: Sep 30, 2022

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures

1. Composite adverse perinatal outcome [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).

2. Small for Gestational Age (safety) [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 [Up to 6 weeks (4-12 weeks) after delivery]

   One or more of maternal death, new heart failure, stroke, encephalopathy, angina, myocardial infarction or ischemia, pulmonary edema, ICU admission/intubation, or renal failure

2. Severe maternal hypertension + components of the primary composite endpoint [Up to 2 weeks postpartum or 90 days for neonatal death]

   Persistent severe hypertension with or without proteinuria + the primary composite

3. Preterm birth and Indicated preterm birth (<37 weeks) [Until delivery]

4. Composite of severe neonatal morbidities [Up to 90 days post delivery]

   One or more of Bronchopulmonary dysplasia (BPD), Retinopathy of prematurity (ROP), Necrotizing enterocolitis (NEC), Intraventricular hemorrhage (VH) grade III/IV

5. Adherence to treatment after delivery [6 weeks (4-12 weeks) after delivery]

   Adherence to antihypertensive therapy after delivery

Other Outcome Measures

1. Superimposed preeclampsia [Up to 2 weeks after delivery]

   Mild or severe, including eclampsia

2. Superimposed gestational hypertension [Enrollment (between 6 and 18 weeks gestation) to delivery]

   Persistent hypertension above baseline without proteinuria occurring after 20 weeks gestation

3. Severe hypertension [Up to 6 weeks (4-12 weeks) after delivery]

   Blood pressure ≥160/110

4. Cesarean delivery [Until delivery]

   Cesarean delivery

5. Blood transfusion [Up to 6 weeks]

   During pregnancy or postpartum

6. NICU admission [Up to 6 weeks (4-12 weeks) after delivery]

   NICU admission and length of NICU stay

7. Low birth weight [At birth]

   Birth weight <2500g

8. Ponderal index [At birth]

   Mean ponderal index

9. Head circumference [At birth]

   Mean head circumference

10. Placental weight [At delivery]

    Mean placental weight

11. Hypoglycemia [From delivery to hospital discharge (2 - 3 days after delivery)]

    Prevalence of hypoglycemia

12. Bradycardia [From delivery to hospital discharge (2 - 3 days after delivery)]

    Prevalence of bradycardia

13. Hypotension [From delivery to hospital discharge (2 - 3 days after delivery)]

    Incidence (%) with hypotension

14. Respiratory distress syndrome (RDS) [From delivery to hospital discharge (2 - 3 days after delivery)]

    Incidence (%) with RDS

15. Bronchopulmonary dysplasia (BPD) [Up to 3 months after delivery]

    Incidence (%) with BPD

16. Intubation/ventilation [From delivery to hospital discharge (2 - 3 days after delivery)]

    Incidence (%) with intubation for ventilation

17. Intraventricular hemorrhage (IVH) [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) [Up to 3 months after delivery]

    Incidence (%) with NEC

19. Hyperbilirubinemia [From delivery to hospital discharge (2 - 3 days after delivery)]

    Incidence (%) with hyperbilirubinemia

20. 5-min Apgar score [At delivery]

    Apgar score <7

21. Sepsis [From delivery to hospital discharge (2 - 3 days after delivery)]

    Incidence (%) with sepsis

22. Unscheduled prenatal clinic or ER visits [Up to 3 months after delivery]

    Number of unscheduled clinic or ER visits before and after delivery

23. Hospitalizations [Up to 3 months postpartum]

    Number of hospitalizations before or after delivery

24. Postpartum unscheduled or ER visits [Up to 3 months after delivery]

    Number of postpartum unscheduled or ER visits

25. Postpartum hospitalizations [Up to 3 months after delivery]

    Number of postpartum hospitalizations

Eligibility Criteria

Criteria

• Ages Eligible for Study: 12 Years and Older
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

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

1. Known major fetal anomaly;

2. Known fetal demise;

3. Suspected IUGR;

4. Membrane rupture or planned termination prior to randomization;

5. 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;

6. Contraindication to labetalol and nifedipine (e.g. know hypersensitivity);

7. Current substance abuse or addiction (cocaine, methamphetamine)

8. Participation in another trial without prior approval (CHAP participants will not be enrolled in other trials without prior approval by protocol committee)

9. Physician or provider refusal

10. Patient refusal *The minimum age varies by center

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama at Birmingham, Clinical Coordinating Center	Birmingham	Alabama	United States	35294
2	University of Alabama at Birmingham, Data Coordinating Center	Birmingham	Alabama	United States	35294
3	University of South Alabama	Mobile	Alabama	United States	36604
4	University of Arkansas for Medical Sciences	Little Rock	Arkansas	United States	72205
5	Arrowhead Regional Medical Center	Colton	California	United States	92324
6	University of California, San Diego	San Diego	California	United States	92110
7	General Hospital of San Francisco	San Francisco	California	United States	94110
8	University of California San Francisco	San Francisco	California	United States	94143
9	Stanford University	Stanford	California	United States	94305
10	University of Colorado	Boulder	Colorado	United States	80204
11	Denver Health	Denver	Colorado	United States	80204
12	Yale University	New Haven	Connecticut	United States	06511
13	Christiana Care Health Services	Newark	Delaware	United States	19713
14	University of South Florida	Tampa	Florida	United States	33606
15	Emory University	Atlanta	Georgia	United States	30322
16	Northwestern	Evanston	Illinois	United States	60208
17	Indiana University	Bloomington	Indiana	United States	47405
18	University of Iowa	Iowa City	Iowa	United States	52242
19	University of Kansas Medical Center	Lawrence	Kansas	United States	66045
20	University of Kentucky	Lexington	Kentucky	United States	40536
21	Tulane	New Orleans	Louisiana	United States	70112
22	Ochsner Health System/Medical Center	New Orleans	Louisiana	United States	70115
23	Beaumont Hospital	Royal Oak	Michigan	United States	48073
24	University of Mississippi Medical College	Jackson	Mississippi	United States	39216
25	Washington University	Saint Louis	Missouri	United States	63110
26	Robert Wood Johnson Medical School	New Brunswick	New Jersey	United States	08901
27	St. Peters University Hospital	New Brunswick	New Jersey	United States	08901
28	New Jersey Medical School	Newark	New Jersey	United States	07103
29	Virtua Medical Group	Sewell	New Jersey	United States	08080
30	New York Presbyterian Queens	Flushing	New York	United States	11355
31	Winthrop University Hospital	Mineola	New York	United States	11501
32	Columbia University	New York	New York	United States	10032
33	Weill Cornell	New York	New York	United States	10065
34	University of North Carolina	Chapel Hill	North Carolina	United States	27599
35	Duke Regional Medical Center	Durham	North Carolina	United States	27704
36	Duke University	Durham	North Carolina	United States	27705
37	WakeMed	Raleigh	North Carolina	United States	27610
38	TriHealth, Inc	Cincinnati	Ohio	United States	45220
39	Case Western/Metro Health	Cleveland	Ohio	United States	44109
40	Cleveland Clinic Fairview	Cleveland	Ohio	United States	44111
41	Ohio State University	Columbus	Ohio	United States	43210
42	Miami Valley Hospital	Dayton	Ohio	United States	45409
43	Cleveland Clinic-Hillcrest Hospital	Mayfield Heights	Ohio	United States	44124
44	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma	United States	73104
45	Oregon Health & Science University	Portland	Oregon	United States	97239
46	Lehigh Valley Hospital/Health Network	Allentown	Pennsylvania	United States	18101
47	St. Luke's University Health Network	Bethlehem	Pennsylvania	United States	18015
48	Geisinger Clinic	Danville	Pennsylvania	United States	17822
49	Drexel University College of Medicine	Philadelphia	Pennsylvania	United States	19019
50	Hospital of the University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104
51	Pennsylvania Hospital	Philadelphia	Pennsylvania	United States	19104
52	University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104
53	Temple University	Philadelphia	Pennsylvania	United States	19140
54	University of Pittsburg/Magee Women's Center	Pittsburgh	Pennsylvania	United States	15201
55	Brown (WIHRI)	Providence	Rhode Island	United States	02912
56	Medical University of South Carolina	Charleston	South Carolina	United States	29425
57	University of Tennessee Health Science Center	Memphis	Tennessee	United States	38103
58	Vanderbilt University	Nashville	Tennessee	United States	37232
59	UT Southwestern	Dallas	Texas	United States	75390
60	UT Medical Branch	Galveston	Texas	United States	77555
61	Baylor College of Medicine	Houston	Texas	United States	77030
62	UT Houston	Houston	Texas	United States	77030
63	McKay Dee Hospital	Ogden	Utah	United States	84403
64	Utah Valley Regional Medical Center	Provo	Utah	United States	84604
65	Intermountain Healthcare	Salt Lake City	Utah	United States	84132
66	University of Utah	Salt Lake City	Utah	United States	84132
67	LDS Hospital	Salt Lake City	Utah	United States	84143
68	Gundersen Health System	La Crosse	Wisconsin	United States	54601
69	Unity Point Health-Meriter Hospital	Madison	Wisconsin	United States	53715
70	Marshfield Clinic	Marshfield	Wisconsin	United States	54449
71	Medical College of Wisconsin	Milwaukee	Wisconsin	United States	53226
72	Aurora Research Institute	Milwaukee	Wisconsin	United States	53233

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
• 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
• Premier Health Miami Valley Hospital

Investigators

• 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
• Principal Investigator: Jeffery Szychowski, PhD, University of Alabama at Birmingham-Data Coordinating Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Alan Tita, Principal Investigator, University of Alabama at Birmingham
• ClinicalTrials.gov Identifier: NCT02299414
• Other Study ID Numbers: 1U01HL119242-01; U01HL119242-01
• First Posted: Nov 24, 2014
• Last Update Posted: Aug 23, 2022
• Last Verified: Aug 1, 2022

• Keywords provided by Alan Tita, Principal Investigator, University of Alabama at Birmingham: Pregnancy; Chronic hypertension
• Additional relevant MeSH terms: Hypertension; Antihypertensive Agents; Nifedipine

Study Results

No Results Posted as of Aug 23, 2022