HyperAldosteronism in Pregnancy Predicted Impacts (H.A.P.P.I. Trial)

HyperAldosteronism in Pregnancy Predicted Impacts

Primary hyperaldosteronism confers a higher risk of cardiovascular complications compared to essential hypertension. Preliminary data is controversial in regards of excessive maternal fetal and neonatal excessive risks in pregnancy.

This study aims at establishing the prevalence of PHA in an population with a recent episode of hypertensive disorder of pregnancy (HDP). The goal is to determine if a universal screening for PHA after a HDP is worthed. The investigators also wish to evaluate the complication rate in pregnant women with PHA compared to women without PHA.

This is a prospective cohort study where all eligible women will be screened for PHA after a HDP episode in the last pregnancy. We will then compare PHA women to non PHA women according to pregnancy complications.

Study Overview

• Status: Active, not recruiting
• Conditions: Primary Hyperaldosteronism; Hypertensive Disorder of Pregnancy
• Intervention / Treatment: Diagnostic test: Aldosterone/Renin Ratio

Detailed Description

This is a pilot study to evaluate feasibility and proof of concept. This is a prospective multicenter cohort study. Two university centers will participate (Sherbrooke and Montreal).

Participants will be recruited from post-partum Obstetric Medicine clinic in two tertiary care centers. They will be included if they presented a hypertensive disorder of preganncy (HDP) in their last pregnacy (from 4 weeks to 24 months after delivery). Women with pheochromocytoma, Cushing syndrome, secondary hyperaldosteronism, and those who are currently pregnant will be excluded.

All participants will be screened for PHA (with an aldosterone/renin ratio) and if the screening test is positive, they will be referred to a specialist to confirm the diagnosis.

Data will be collected from the participants and their babies' charts. Demographic data, obstetrical data, delivery data, maternal/fetal/neonatal complications, and diagnostic of PHA data will be collected.

A convenient sample size of 200 women will be used. If the prevalence of HPA is 5% or more, this would justify a larger study.

Primary outcome: establish the prevalence of PHA in women with a hypertensive disorders of pregnancy in last pregancy.

Secondary outcome include:

1. to compare maternal, fetal and neonatal outcomes among women diagnosed with primary hyperaldosteronism (PHA) and pregnant women without PHA.
2. to establish the prevalence of PHA for each sub-type of hypertensive disorder of pregnancy
3. to compare maternal, fetal and neonatal outcomes among women diagnosed with primary hyperaldosteronism (PHA) before pregnancy and pregnant women diagnosed with PHA after pregnancy.

• Study Type: Observational
• Enrollment (Estimated): 200

Contacts and Locations

Study Locations

• Canada
  • Quebec
    • Sherbrooke, Quebec, Canada, J1H 5N4
      • Centre Hospitalier Universitaire de Sherbrooke
    • Sherbrooke, Quebec, Canada, J1H 5N4
      • Centre Hopitalier Universiatire de Sherbrooke

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Post-partum women who are followed in a specialized post-partum clinic in Montreal or Sherbrooke (Qc, Canada) for their hypertensive disorder during their latest pregnancy.

Description

Inclusion Criteria:

• Between 4 and 24 weeks post-partum women who had a hypertensive disorder during their latest pregnancy.

Exclusion Criteria:

• Ongoing pregnancy
• Diagnosed pheochromocytoma
• Diagnosed Cushing syndrome
• Diagnosed secondary hyperaldosteronism

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Primary Hyperaldosteronism Diagnosed Women; Post-partum women who had a hypertensive disorder of pregnancy and a screened primary hyperaldosteronism (positive aldosterone/renin ratio).	Diagnostic test: Aldosterone/Renin Ratio; Blood sample collected to measure the aldosterone/renin ratio for the primary hyperaldosteronism screening.
Control Women; Post-partum women who had a hypertensive disorder of pregnancy without underlying primary hyperaldosteronism (negative aldosterone/renin ratio)	Diagnostic test: Aldosterone/Renin Ratio; Blood sample collected to measure the aldosterone/renin ratio for the primary hyperaldosteronism screening.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Primary hyperaldosteronism (PHA) prevalence in pregnant women with hypertensive disorders of pregnancy.	Prevalence of PHA in women with a hypertensive disorder of pregnancy in last pregnancy	Screening done between 4 and 24 weeks post-partum

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maternal and fetal impacts of PHA on hypertensive disorders of pregnancy	Comparison of the prevalence of each pre-specified complications (obstetrical, maternal, fetal, neonatal) between the PHA group and the non-PHA group.	During last pregnancy and 6 weeks postpartum
Prevalence of PHA for each hypertensive disorder of pregnancy	Comparison of the prevalence of each HDP subtype (i.e. chronic hypertension, gestational hypertension, pre-eclampsia)	During last pregnancy and 6 weeks postpartum
Impact of the timing of PHA on hypertensive disorders of pregnancy	Comparison between pregnancy outcomes for PHA diagnosed before the pregnancy with those diagnosed in post-partum	During last pregnancy and 6 weeks postpartum

Collaborators and Investigators

• Sponsor: Université de Sherbrooke
• Collaborators: Foundation of the Stars
• Investigators: Principal Investigator: Nadine Sauvé, MD, Universite de Sherbrooke

Publications and helpful links

General Publications

• Magee LA, Pels A, Helewa M, Rey E, von Dadelszen P; Canadian Hypertensive Disorders of Pregnancy Working Group. Diagnosis, evaluation, and management of the hypertensive disorders of pregnancy: executive summary. J Obstet Gynaecol Can. 2014 May;36(5):416-41. doi: 10.1016/s1701-2163(15)30588-0. English, French.
• Alam S, Kandasamy D, Goyal A, Vishnubhatla S, Singh S, Karthikeyan G, Khadgawat R. High prevalence and a long delay in the diagnosis of primary aldosteronism among patients with young-onset hypertension. Clin Endocrinol (Oxf). 2021 Jun;94(6):895-903. doi: 10.1111/cen.14409. Epub 2021 Feb 22.
• Downie E, Shanmugalingam R, Hennessy A, Makris A. Assessment and Management of Primary Aldosteronism in Pregnancy: A Case-Control Study. J Clin Endocrinol Metab. 2022 Jul 14;107(8):e3152-e3158. doi: 10.1210/clinem/dgac311.
• Turner K, Hameed AB. Hypertensive Disorders in Pregnancy Current Practice Review. Curr Hypertens Rev. 2017;13(2):80-88. doi: 10.2174/1573402113666170529110024.
• Umesawa M, Kobashi G. Epidemiology of hypertensive disorders in pregnancy: prevalence, risk factors, predictors and prognosis. Hypertens Res. 2017 Mar;40(3):213-220. doi: 10.1038/hr.2016.126. Epub 2016 Sep 29.
• Landau E, Amar L. Primary aldosteronism and pregnancy. Ann Endocrinol (Paris). 2016 Jun;77(2):148-60. doi: 10.1016/j.ando.2016.04.009. Epub 2016 May 6.
• Escher G. Hyperaldosteronism in pregnancy. Ther Adv Cardiovasc Dis. 2009 Apr;3(2):123-32. doi: 10.1177/1753944708100180. Epub 2009 Jan 26.

Study record dates

Study Major Dates

• Study Start (Actual): January 10, 2023
• Primary Completion (Estimated): March 1, 2025
• Study Completion (Estimated): December 1, 2025

Study Registration Dates

• First Submitted: October 25, 2022
• First Submitted That Met QC Criteria: December 1, 2022
• First Posted (Actual): December 5, 2022

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 13, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Keywords: Prevalence; Pregnancy Outcome
• Additional Relevant MeSH Terms: Endocrine System Diseases; Vascular Diseases; Cardiovascular Diseases; Infections; Adrenal Gland Diseases; Adrenocortical Hyperfunction; Hypertension; Toxemia; Hyperaldosteronism
• Other Study ID Numbers: MP-31-2023-4857

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No