Mineralocorticoid Receptor Antagonism for High Blood Pressure After Pre-eclampsia

(CARDAMOM Trial)

Not yet recruiting at 1 trial location

Overseen By Samantha Murillo, MSc

Age: 18 - 65

Sex: Female

Trial Phase: Phase 2

Sponsor: Massachusetts General Hospital

Must be taking: Amlodipine

Must not be taking: MRAs, Amiloride, Oral contraceptives, others

Disqualifiers: Pregnancy, Diabetes, Heart failure, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 3

Duration: 48 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores two medications, eplerenone (a mineralocorticoid receptor antagonist) and chlorthalidone, to determine which better improves heart and blood vessel health in women who had preeclampsia and now have high blood pressure. Researchers aim to assess whether eplerenone enhances heart and small blood vessel function more effectively than chlorthalidone. Women who experienced preeclampsia, currently have high blood pressure, and show changes in heart structure might be suitable for this trial. Participants will take one of the medications daily for 48 weeks and attend regular check-ups. As a Phase 2 trial, this study measures the treatment's effectiveness in an initial, smaller group, allowing participants to contribute to important research.

Do I have to stop taking my current medications to join the trial?

The trial does not specify if you need to stop taking your current medications, but you will need to take Amlodipine for 12 weeks before starting the study medication. You cannot have used certain medications like mineralocorticoid receptor antagonists or amiloride recently.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that chlorthalidone is generally safe and effective for treating high blood pressure. One study compared chlorthalidone with another common blood pressure medicine and found both to be safe options. However, chlorthalidone may cause side effects like low potassium levels, so regular check-ups are important.

Eplerenone is another drug tested in this trial. The FDA has approved it for other uses, such as treating heart failure and high blood pressure. This approval indicates that eplerenone is generally safe for people, although it can cause side effects like increased potassium levels.

Both treatments have been used for other conditions, suggesting they are safe, but monitoring for any side effects during the trial remains crucial. Participants will have regular check-ups to ensure everything proceeds smoothly. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they offer a fresh approach to managing high blood pressure after pre-eclampsia. Eplerenone is unique because it blocks mineralocorticoid receptors, which helps reduce fluid retention and lower blood pressure without the potassium loss that can occur with traditional diuretics. Chlorthalidone, on the other hand, is a well-known diuretic that helps eliminate excess fluid through increased urination, but in this trial, it is combined with potassium supplementation to mitigate potential side effects. These treatments could provide more targeted and balanced options for controlling blood pressure in women previously affected by pre-eclampsia, potentially improving long-term health outcomes.

What evidence suggests that this trial's treatments could be effective for high blood pressure after pre-eclampsia?

In this trial, participants will receive either eplerenone or chlorthalidone to manage high blood pressure after preeclampsia. Studies have shown that eplerenone effectively lowers high blood pressure and may improve heart function, especially in women who had preeclampsia. This medication might reduce the risk of future heart problems by relaxing blood vessels, making blood flow easier. Meanwhile, chlorthalidone effectively reduces blood pressure compared to some other medications, helping prevent complications linked to high blood pressure in pregnancy. Both treatments have shown promise in managing high blood pressure and improving heart health, particularly for those who experienced preeclampsia. ^{1 6 7 8 9}

Who Is on the Research Team?

Michael Honigberg, MD

Principal Investigator

Massachusetts General Hospital

Are You a Good Fit for This Trial?

This trial is for women who had preeclampsia during pregnancy and now have chronic hypertension and heart changes. They must be willing to take amlodipine for 12 weeks before the study drugs, attend several study visits, and undergo tests like blood pressure measurements, echocardiography, and cardiac scans.

Inclusion Criteria

Evidence of concentric left ventricular (LV) remodeling, defined as relative LV wall thickness >0.42, with or without LV hypertrophy

I had preeclampsia in a past pregnancy and did not have high blood pressure before getting pregnant.

I have been diagnosed with chronic high blood pressure.

Exclusion Criteria

Planned pregnancy, current pregnancy, or lactation

BMI >45 kg/m²

Urine microalbumin/creatinine ratio >300 mg/g at screening

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-treatment

Participants receive pre-treatment with Amlodipine for 12 weeks prior to beginning the study medication

12 weeks

1 visit (in-person)

Treatment

Participants receive daily self-administration of two oral capsules (eplerenone + potassium placebo or chlorthalidone + potassium) for 48 weeks

48 weeks

Visits at weeks 2, 12, 24, 36, and 48 (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Chlorthalidone
• Eplerenone

Trial Overview The trial is testing if eplerenone improves heart vessel function and structure better than chlorthalidone in these women. Each participant will take either eplerenone with a potassium placebo or chlorthalidone with potassium daily for 48 weeks to compare effects on their hearts.

How Is the Trial Designed?

Group I: Eplerenone Active Control 1 Intervention

Participants will receive eplerenone 100 mg daily plus potassium placebo for 48 weeks

Group II: Chlorthalidone Active Control 1 Intervention

Participants will receive chlorthalidone 25 mg plus potassium 20 mEq daily for 48 weeks

Who Is Running the Clinical Trial?

Massachusetts General Hospital

Lead Sponsor

Trials

3,066

Recruited

13,430,000+

Brigham and Women's Hospital

Collaborator

Trials

1,694

Recruited

14,790,000+

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials

3,987

Recruited

47,860,000+

Citations

1. ahajournals.org ahajournals.org/doi/10.1161/CIRCULATIONAHA.124.073302

Hypertension in Pregnancy and Postpartum In the CHAP trial, treating mild chronic hypertension resulted in a statistically significant reduction in the primary composite outcome (odds ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8673186/

Hypertension in the Postpartum Woman: Clinical Update for ... In a study of preeclamptic women by Podymow and colleagues, 43% of patients had BPs that normalized by the end of the first postpartum month, but 57% remained ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0733865112000562

Hypertension in Pregnancy There is significant maternal and neonatal morbidity associated with hypertension in pregnancy, with increased rates of intracerebral hemorrhage, placental ...

4. academic.oup.com academic.oup.com/ajh/article/17/S1/114A/162543

Greater efficacy of chlorthalidone over hydrochlorothiazide for ... The average BP at the index visit on HCTZ was 157±14/80±11 mmHg. After an average of 64±12 days, the average BP on follow-up was 147±13/81±14 ...

5. academics.prismahealth.org academics.prismahealth.org/academics/education/obgyn-clinical-practice-guidelines/outpatient-obstetrics/chronic-hypertension-in-pregnancy

Chronic Hypertension in Pregnancy Treatment with antihypertensives seems to significantly improve pregnancy outcomes6. In pregnancy, BP nadirs at 14-28 weeks, thus if patient presents during ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7042845/

Comparison of Cardiovascular and Safety Outcomes of ... This cohort study compares cardiovascular and safety outcomes of chlorthalidone and hydrochlorothiazide as first-line therapies for adults with hypertension.

7. acc.org acc.org/-/media/Non-Clinical/Files-PDFs-Excel-MS-Word-etc/Membership/Sections-Councils/Reproductive-Health-and-Cardio-Obstetrics/ACC-Post-Partum-Hypertension-Clinical-Toolkit.pdf

Postpartum Hypertension Clinic Development Toolkit This toolkit will serve to help clinicians, health care teams, and health systems develop postpartum hypertension care programs for individuals with a recent ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9031058/

Hypertension in Pregnancy: Diagnosis, Blood Pressure Goals ... The prevalence of postpartum hypertension may be as high as 8% in women without antepartum hypertension (followed 48 hours after delivery and up to 6 weeks ...

9. academic.oup.com academic.oup.com/eurjpc/advance-article/doi/10.1093/eurjpc/zwaf373/8177209

Current concepts in the management of hypertension in ... This systematic review aims to compare international practice guidelines for the management gestational hypertension (GH) and pre-eclampsia (PE).