Swedish heart and kidney failure pilot

Swedish Cardiac And Renal Failure Study-1 (SCARF-1): An Open-Label Pilot Trial to Evaluate the Feasibility, Safety and Efficacy of Eplerenone in Patients With Heart Failure With Reduced Ejection Fraction and Severe Chronic Kidney Disease

This trial will test whether the drug eplerenone is safe and feasible for people with heart failure with reduced ejection fraction who also have severe chronic kidney disease.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 40 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Karolinska Institutet (other)
• Locations: 1 site (Stockholm)
• Trial ID: NCT07029503 on ClinicalTrials.gov

What this trial studies

This is a Phase 2 pilot interventional trial giving eplerenone to patients with HFrEF and more advanced chronic kidney disease who were usually excluded from prior trials. The primary aim is to test feasibility and safety with close monitoring of potassium levels and kidney function, while also performing exploratory analyses of heart-failure outcomes. Participants must be on optimized background heart-failure therapy and meet criteria including EF ≤40% and NYHA class II–III. The study is conducted at Karolinska/Danderyd with regular clinic visits and laboratory checks throughout follow-up.

Who should consider this trial

Good fit: Ideal candidates are adults with HFrEF (EF ≤40%), NYHA class II–III, clinically stable on optimized background therapy, and with chronic kidney disease severe enough that they were excluded from previous MRA trials.

Not a fit: Patients with preserved ejection fraction, unstable or recently changed heart-failure therapy, uncontrolled hyperkalemia, or those on dialysis are unlikely to benefit or be eligible for this trial.

Why it matters

Potential benefit: If successful, this could allow a proven heart-failure medicine to be used safely in patients with severe kidney disease, potentially improving symptoms and reducing hospitalizations.

How similar studies have performed: Large randomized trials have shown mineralocorticoid receptor antagonists reduce mortality and hospitalizations in HFrEF patients with preserved kidney function, and post-hoc and registry data suggest possible benefit in patients with impaired kidneys, but prospective trials in severe CKD are lacking.

Eligibility criteria

Inclusion Criteria:

* The participant has given their written consent to participate
* A diagnosis of HFrEF according to current criteria, for at least three months before the screening visit
* Echocardiography within 24 months of the screening visit with ejection fraction ≤ 40%. The responsible investigator is allowed to order a new TTE at their own discretion if clinically indicated - e.g. following the initiation of markedly intensified HFrEF-treatment or in the event of significant clinical deterioration. If the new TTE shows an EF \> 40%, the participant will not be eligible for inclusion. However, a potential echocardiographic worsening should not, by itself, preclude enrollment
* New York Heart Association class II-III
* Optimally treated and stable HFrEF (according to the investigator) since at least four weeks before the screening visit. Treatment should include beta-blockers, sodium/glucose co-transporter 2 inhibitors, angiotensin-converting enzyme inhibitors, or angiotensin receptor blockers if eGFR ≥ 20 ml/min/1.73m2 according to the revised Lund-Malmö method. Participants should also have cardiac resynchronization therapy or an implantable cardioverter-defibrillator if the indication exists according to current guidelines
* eGFR \< 30 ml/min/1.73m2 according to the revised Lund-Malmö method at least once during the 12 months before the screening visit, and eGFR \< 45 ml/min/1.73m2 at the time of inclusion

Exclusion Criteria:

* P-K ≥ 5.6
* For the first ten study participants:

eGFR \< 20 ml/min/1.73m2 according to the revised Lund-Malmö method, or projected decline in eGFR to \< 10 ml/min/1.73m2 during the 36-week study period. The projected decline will be estimated using the three most recent eGFR values from the previous 6-12 months

\- For the remainder of the study participants: eGFR \< 10 ml/min/1.73m2 according to the revised Lund-Malmö method, or projected decline in eGFR to \< 10 ml/min/1.73m2 during the 36-week study period. The projected decline will be estimated using the three most recent eGFR values from the previous 6-12 months

* Ongoing/planned dialysis
* Systolic blood pressure \< 90 mmHg
* Uncontrolled hypertension as judged by the investigator
* Severe hepatic impairment (Child-Pugh C)
* History of, or planned, heart transplantation or left ventricular assist device
* Unwillingness to comply with highly effective contraceptive methods, or ongoing/planned pregnancy, or breastfeeding
* Previous allergic reaction to an MRA or a potassium binder
* Ongoing treatment with lithium, cyclosporine, tacrolimus, nonsteroidal anti-inflammatory drugs, trimethoprim, or strong CYP3A inhibitors (ketoconazole, itraconazole, ritonavir, nelfinavir, clarithromycin, telithromycin, and nefazodone) or inducers (rifampicin, carbamazepine, phenytoin, phenobarbital, and St. John's Wort)
* QTc(f) ≥ 550 msec, history of QT prolongation associated with any medication requiring medication discontinuation, or congenital long QT syndrome
* Uncontrolled arrhythmia as judged by the investigator
* Acute cardiac hospitalization or procedure within four weeks before inclusion
* Not suitable as judged by the investigator (presumed inability to participate, severe or terminal co-morbidity, and expected survival \< 12 months)
* Previously enrolled in this trial or participation in another trial not approved for co-enrollment

Where this trial is running

Stockholm

• Department of Cardiology, Danderyd Hospital, Karolinska Institutet — Stockholm, Sweden (RECRUITING)

Study contacts

• Study coordinator: Carl Haggård, MD, PhD

Conditions: HFrEF - Heart Failure With Reduced Ejection Fraction, Chronic Kidney Disease, HFrEF - Heart Failure with Reduced Ejection Fraction, Chronic kidney disease, Heart failure, Chronic heart failure, HFrEF, CKD