Reducing the Risk of Chronic Hypertension and Improving Vascular Function Following Preeclampsia

Hypertensive Disorder of Pregnancy Clinical Trial

— REPAIR  

Official title:

Reducing the Risk of Chronic Hypertension and Improving Vascular Function Following

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06220721
• Other study ID #: PRO00049909
• Status: Not yet recruiting
• Phase: Phase 3
• Start date: July 1, 2024
• Est. completion date: June 30, 2030

Study information

• Verified date: January 2024
• Source: Medical College of Wisconsin
• Contact: Anna Palatnik, MD
• Phone: 14147916817
• Email: apalatnik[@]mcw.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The long-term goal of our work is to evaluate the effect of intensive postpartum blood pressure control on maternal cardiovascular health, risk of chronic hypertension, and reversal of vascular dysfunction generated by hypertensive disorders of pregnancy, thus attenuating the lifelong trajectory of cardiovascular disease risk.

Description:

The REPAIR trial will randomize 618 postpartum patients with HDP to intensive blood pressure (BP) control with Nifedipine extended release (ER) (target BP <140/90 mmHg) versus active control group (target BP <150/100 mmHg) for 6 weeks postpartum, using home BP monitoring program at two clinical sites: Medical College of Wisconsin (MCW) and Northwestern University (NU). All participants will undergo vascular function assessment: endothelial dysfunction with brachial artery flow mediated dilation (FMD), arterial stiffness with carotid-femoral pulse wave velocity (cfPWV), and collection of an anti-angiogenic biomarker, soluble fms-like tyrosine kinase (sFlt-1), at baseline, 6 weeks, and 12 months postpartum. The primary outcome is the rate of new diagnosis of chronic HTN at one year postpartum. Secondary outcomes are improvement in vascular function, assessed by FMD, cfPWV, and sFlt-1, from baseline to 12 months postpartum. Sub-group analyses will be done to examine study outcomes by HDP type (gestational HTN vs. preeclampsia) and by patients that maintained BP <130/80 mmHg versus higher

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 618
• Est. completion date: June 30, 2030
• Est. primary completion date: June 30, 2029
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Hypertensive disorders of pregnancy (HDP) diagnosis (gestational hypertension or preeclampsia) according to ACOG guidelines
• Postpartum day 0-3 and prior to discharge
• Able to communicate in English or in Spanish
• Age 18 - 50

Exclusion Criteria:

• Pre-gestational hypertension
• Pre-gestational diabetes ( type 1 or type 2)
• Intent to transfer postpartum to an outside institution of the participating centers
• Known allergy to nifedipine or other significant contraindication to nifedipine
• Inability or unwillingness to provide informed consent

Related Conditions & MeSH terms

• Hypertension
• Hypertensive Disorder of Pregnancy
• Toxemia

Intervention

Drug:
• NIFEdipine ER
Initiation of Nifedipine ER postpartum at SBP=140 mmHg or DBP=90 mmHg and maintaining BP at <140/90 mmHg during the first 6 weeks postpartum.

Locations

Country	Name	City	State
United States	Northwestern University	Chicago	Illinois

Sponsors (1)

Lead Sponsor	Collaborator
Medical College of Wisconsin

Country where clinical trial is conducted

United States, 

References & Publications (15)

Duffy JMN, Cairns AE, Magee LA, von Dadelszen P, van 't Hooft J, Gale C, Brown M, Chappell LC, Grobman WA, Fitzpatrick R, Karumanchi SA, Lucas DN, Mol B, Stark M, Thangaratinam S, Wilson MJ, Williamson PR, Ziebland S, McManus RJ; International Collaboration to Harmonise Outcomes for Pre-eclampsia (iHOPE). Standardising definitions for the pre-eclampsia core outcome set: A consensus development study. Pregnancy Hypertens. 2020 Jul;21:208-217. doi: 10.1016/j.preghy.2020.06.005. Epub 2020 Jun 20. — View Citation

Grand'Maison S, Pilote L, Okano M, Landry T, Dayan N. Markers of Vascular Dysfunction After Hypertensive Disorders of Pregnancy: A Systematic Review and Meta-Analysis. Hypertension. 2016 Dec;68(6):1447-1458. doi: 10.1161/HYPERTENSIONAHA.116.07907. Epub 2016 Oct 17. — View Citation

Hauspurg A, Lemon L, Cabrera C, Javaid A, Binstock A, Quinn B, Larkin J, Watson AR, Beigi RH, Simhan H. Racial Differences in Postpartum Blood Pressure Trajectories Among Women After a Hypertensive Disorder of Pregnancy. JAMA Netw Open. 2020 Dec 1;3(12):e2030815. doi: 10.1001/jamanetworkopen.2020.30815. — View Citation

Hirshberg A, Downes K, Srinivas S. Comparing standard office-based follow-up with text-based remote monitoring in the management of postpartum hypertension: a randomised clinical trial. BMJ Qual Saf. 2018 Nov;27(11):871-877. doi: 10.1136/bmjqs-2018-007837. Epub 2018 Apr 27. — View Citation

Lane-Cordova AD, Khan SS, Grobman WA, Greenland P, Shah SJ. Long-Term Cardiovascular Risks Associated With Adverse Pregnancy Outcomes: JACC Review Topic of the Week. J Am Coll Cardiol. 2019 Apr 30;73(16):2106-2116. doi: 10.1016/j.jacc.2018.12.092. — View Citation

Levine L, Arany Z, Kern-Goldberger A, Koelper N, Lewey J, Sammel MD, Elovitz MA, Ky B. Soluble Flt1 levels are associated with cardiac dysfunction in Black women with and without severe preeclampsia. Hypertens Pregnancy. 2021 Feb;40(1):44-49. doi: 10.1080/10641955.2020.1861462. Epub 2020 Dec 20. — View Citation

Lloyd-Jones DM, Allen NB, Anderson CAM, Black T, Brewer LC, Foraker RE, Grandner MA, Lavretsky H, Perak AM, Sharma G, Rosamond W; American Heart Association. Life's Essential 8: Updating and Enhancing the American Heart Association's Construct of Cardiovascular Health: A Presidential Advisory From the American Heart Association. Circulation. 2022 Aug 2;146(5):e18-e43. doi: 10.1161/CIR.0000000000001078. Epub 2022 Jun 29. — View Citation

Lopes Perdigao J, Hirshberg A, Koelper N, Srinivas SK, Sammel MD, Levine LD. Postpartum blood pressure trends are impacted by race and BMI. Pregnancy Hypertens. 2020 Apr;20:14-18. doi: 10.1016/j.preghy.2020.02.006. Epub 2020 Feb 26. — View Citation

Parikh NI, Gonzalez JM, Anderson CAM, Judd SE, Rexrode KM, Hlatky MA, Gunderson EP, Stuart JJ, Vaidya D; American Heart Association Council on Epidemiology and Prevention; Council on Arteriosclerosis, Thrombosis and Vascular Biology; Council on Cardiovascular and Stroke Nursing; and the Stroke Council. Adverse Pregnancy Outcomes and Cardiovascular Disease Risk: Unique Opportunities for Cardiovascular Disease Prevention in Women: A Scientific Statement From the American Heart Association. Circulation. 2021 May 4;143(18):e902-e916. doi: 10.1161/CIR.0000000000000961. Epub 2021 Mar 29. — View Citation

Shahul S, Tung A, Minhaj M, Nizamuddin J, Wenger J, Mahmood E, Mueller A, Shaefi S, Scavone B, Kociol RD, Talmor D, Rana S. Racial Disparities in Comorbidities, Complications, and Maternal and Fetal Outcomes in Women With Preeclampsia/eclampsia. Hypertens Pregnancy. 2015 Nov;34(4):506-515. doi: 10.3109/10641955.2015.1090581. Epub 2015 Dec 4. — View Citation

Stuart JJ, Tanz LJ, Rimm EB, Spiegelman D, Missmer SA, Mukamal KJ, Rexrode KM, Rich-Edwards JW. Cardiovascular Risk Factors Mediate the Long-Term Maternal Risk Associated With Hypertensive Disorders of Pregnancy. J Am Coll Cardiol. 2022 May 17;79(19):1901-1913. doi: 10.1016/j.jacc.2022.03.335. — View Citation

Too G, Wen T, Boehme AK, Miller EC, Leffert LR, Attenello FJ, Mack WJ, D'Alton ME, Friedman AM. Timing and Risk Factors of Postpartum Stroke. Obstet Gynecol. 2018 Jan;131(1):70-78. doi: 10.1097/AOG.0000000000002372. — View Citation

Weissgerber TL, Milic NM, Milin-Lazovic JS, Garovic VD. Impaired Flow-Mediated Dilation Before, During, and After Preeclampsia: A Systematic Review and Meta-Analysis. Hypertension. 2016 Feb;67(2):415-23. doi: 10.1161/HYPERTENSIONAHA.115.06554. Epub 2015 Dec 28. — View Citation

Whelton PK, Carey RM, Aronow WS, Casey DE Jr, Collins KJ, Dennison Himmelfarb C, DePalma SM, Gidding S, Jamerson KA, Jones DW, MacLaughlin EJ, Muntner P, Ovbiagele B, Smith SC Jr, Spencer CC, Stafford RS, Taler SJ, Thomas RJ, Williams KA Sr, Williamson JD, Wright JT Jr. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. 2018 May 15;71(19):e127-e248. doi: 10.1016/j.jacc.2017.11.006. Epub 2017 Nov 13. No abstract available. Erratum In: J Am Coll Cardiol. 2018 May 15;71(19):2275-2279. — View Citation

Wu P, Haththotuwa R, Kwok CS, Babu A, Kotronias RA, Rushton C, Zaman A, Fryer AA, Kadam U, Chew-Graham CA, Mamas MA. Preeclampsia and Future Cardiovascular Health: A Systematic Review and Meta-Analysis. Circ Cardiovasc Qual Outcomes. 2017 Feb;10(2):e003497. doi: 10.1161/CIRCOUTCOMES.116.003497. Epub 2017 Feb 22. — View Citation

* Note: There are 15 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Chronic hypertension	Diagnosis of chronic hypertension one year postpartum	One year postpartum
Secondary	Flow-mediated dilation	Brachial artery flow-mediated dilation will assess endothelial dysfunction.	One year postpartum
Secondary	Arterial stiffness	Carotid-femoral pulse wave velocity will be done to assess arterial stiffness	One year postpartum
Secondary	Unplanned healthcare utilization	Number of hospital visits after delivery discharge	Through one year postpartum
Secondary	Composite severe maternal morbidity	Includes the following maternal core outcomes of preeclampsia using PMID: 32674052 reference	Through one year postpartum
Secondary	Life's Essential 8 cardiovascular health score (range 0-100)	The score will be calculated using American Heart Association application	One year postpartum