Safety, Tolerability and Efficacy of Rapid Optimization, Helped by NT-proBNP testinG, of Heart Failure Therapies

Heart Failure Clinical Trial

— STRONG-HF  

Official title:

Safety, Tolerability and Efficacy of Rapid Optimization, Helped by NT-proBNP testinG, of Heart Failure Therapies

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03412201
• Other study ID #: CHF201701
• Status: Recruiting
• Phase: N/A
• Start date: May 11, 2018
• Est. completion date: October 2021

Study information

• Verified date: February 2021
• Source: Heart Initiative
• Contact: Maria Novosadova, MD
• Phone: +41614851250
• Email: marianovosadova[@]momentum-research.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

STRONG-HF is a multicenter, randomized, parallel group study designed to evaluate the efficacy and safety of up-titration of standard oral heart failure medications during hospitalization for acute heart failure. Patients admitted for acute heart failure will be randomized within 2 days before discharge to either usual care or intensification of treatment with a beta-blocker, a renin-angiotensin system blocker, and a mineralocorticoid receptor blocker ("high intensity care" arm). In the "high intensity care" arm, patients' clinical signs and symptoms of heart failure will be assessed, and routine laboratory measures and biomarkers will be measured, at frequent post-discharge visits. When these measures indicate that it is safe to do so, the doses of the oral heart failure medications will be increased to optimal levels. Patients will be followed through 180 days from randomization. Patients assigned to the usual care group will be followed by their general physician and/or cardiologist according to local medical standards. Patients who were screened but did not meet eligibility criteria will be followed for 90-day outcome. Randomized patients will be contacted at 180 days to assess outcomes.

Description:

STRONG-HF is a multicenter, randomized, parallel group study designed to evaluate the efficacy and safety of up-titration of standard of care medical therapy including beta-blockers; angiotensin converting enzyme inhibitors (ACEi), angiotensin receptor blocker (ARB) or angiotensin receptor neprolysin inhibitor (ARNi); and mineralocorticoid receptor antagonist (MRAs), on morbidity and mortality when initiated and up-titrated early during hospitalization for acute heart failure (AHF). Optimal safety conditions will allow physicians to introduce and/or continue oral HF therapies during this "vulnerable phase" in AHF patients. Patients admitted for AHF with clinical signs of congestion and elevated circulating N-terminal pro-B-type natriuretic peptide (NT-proBNP) and who are not treated with optimal doses of oral heart failure (HF) therapies within 2 days before hospital discharge for AHF and who are hemodynamically stable will be randomized in a 1:1 ratio to either usual care (named "usual care" arm) or intensification of treatment with beta-blockers, and ACEi (or ARB) or ARNi and a MRA (named "high intensity care" arm). In the latter arm, repeated assessments of clinical signs and symptoms of heart failure, routine clinical laboratory measures including potassium, sodium, and creatinine as well as NT-ProBNP will foster, encourage and ensure the safety of the optimization of oral heart failure therapies. AHF patients who were screened but did not meet inclusion criteria, including low circulating NT-proBNP at visit 2, will be followed for 90-day outcome. Randomized patients will be contacted at 180 days to assess outcomes.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1800
• Est. completion date: October 2021
• Est. primary completion date: October 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

Inclusion Criteria:

1. Hospital admission within the 72 hours prior to Screening for acute heart failure with dyspnea at rest and pulmonary congestion on chest X-ray, and other signs and/or symptoms of heart failure such as edema and/or positive rales on auscultation.

2. All measures within 24 hours prior to Randomization of systolic blood pressure = 100 mmHg, and of heart rate = 60 bpm.

3. All measures within 24 hours prior to Randomization of serum potassium = 5.0 mEq/L (mmol/L).

4. Biomarker criteria for persistent congestion:

5. At Screening, NT-proBNP > 2,500 pg/mL.

6. At the time of Randomization (within 2 days prior to discharge), NT-proBNP > 1,500 pg/mL (to ensure the persistence of congestion) that has decreased by more than 10% compared to Screening (to ensure the acuity of the index episode).

7. At 1 week prior to admission, at Screening, and at Visit 2 (just prior to Randomization) either (a) <= ½ the optimal dose of ACEi/ARB/ARNi (see Table) prescribed, no beta-blocker prescribed, and <= ½ the optimal dose of MRA prescribed or (b) no ACEi/ARB/ARNi prescribed, <= ½ the optimal dose of beta-blocker prescribed, and <= ½ the optimal dose of MRA prescribed.

8. Written informed consent to participate in the study.

Exclusion Criteria:

1. Age < 18 or > 85 years.

2. Clearly documented intolerance to high doses of beta-blockers.

3. Clearly documented intolerance to high doses of renin-angiotensin system (RAS) blockers (both ACEi and ARB).

4. Mechanical ventilation [not including continuous positive airway pressure (CPAP)/bilevel positive airway pressure (BIPAP)] in the 24 hours prior to Screening.

5. Significant pulmonary disease contributing substantially to the patients' dyspnea such as forced expiratory volume during the 1st second (FEV1)< 1 liter or need for chronic systemic or nonsystemic steroid therapy, or any kind of primary right heart failure such as primary pulmonary hypertension or recurrent pulmonary embolism.

6. Myocardial infarction, unstable angina or cardiac surgery within 3 months, or cardiac resynchronization therapy (CRT) device implantation within 3 months, or percutaneous transluminal coronary intervention (PTCI), within 1 month prior to Screening.

7. Index Event (admission for AHF) triggered primarily by a correctable etiology such as significant arrhythmia (e.g., sustained ventricular tachycardia, or atrial fibrillation/flutter with sustained ventricular response >130 beats per minute, or bradycardia with sustained ventricular arrhythmia <45 beats per minute), infection, severe anemia, acute coronary syndrome, pulmonary embolism, exacerbation of chronic obstructive pulmonary disease (COPD), planned admission for device implantation or severe non-adherence leading to very significant fluid accumulation prior to admission and brisk diuresis after admission. Troponin elevations without other evidence of an acute coronary syndrome are not an exclusion.

8. Uncorrected thyroid disease, active myocarditis, or known amyloid or hypertrophic obstructive cardiomyopathy.

9. History of heart transplant or on a transplant list, or using or planned to be implanted with a ventricular assist device.

10. Sustained ventricular arrhythmia with syncopal episodes within the 3 months prior to screening that is untreated.

11. Presence at Screening of any hemodynamically significant valvular stenosis or regurgitation, except mitral or tricuspid regurgitation secondary to left ventricular dilatation, or the presence of any hemodynamically significant obstructive lesion of the left ventricular outflow tract.

12. Active infection at any time during the AHF hospitalization prior to Randomization based on abnormal temperature and elevated white blood cells (WBC) or need for intravenous antibiotics.

13. Stroke or transient ischemic attack (TIA) within the 3 months prior to Screening.

14. Primary liver disease considered to be life threatening.

15. Renal disease or estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73m2 [as estimated by the simplified Modification of Diet in Renal Disease (MDRD) formula] at Screening or history of dialysis.

16. Psychiatric or neurological disorder, cirrhosis, or active malignancy leading to a life expectancy < 6 months.

17. Prior (defined as less than 30 days from screening) or current enrollment in a congestive heart failure (CHF) trial or participation in an investigational drug or device study within the 30 days prior to screening

18. Discharge for the AHF hospitalization anticipated to be > 14 days from admission, or to a long-term care facility. Randomization must occur within 12 days following admission and within 2 days prior to anticipated discharge.

19. Inability to comply with all study requirements, due to major co-morbidities, social or financial issues, or a history of noncompliance with medical regimens, that might compromise the patient's ability to understand and/or comply with the protocol instructions or follow-up procedures

20. Pregnant or nursing (lactating) women.

Related Conditions & MeSH terms

• Heart Failure

Intervention

Other:
• Usual Care
Follow-up and management of heart failure medications provided by the patient's general physician and/or cardiologist according to local medical standards
• High Intensity Care
Follow-up and management of heart failure medications provided by specialists at participating institutions. Doses of oral heart failure medications optimized within 2 weeks, provided clinical assessments and laboratory measures indicate that it is safe to increase doses.

Locations

Country	Name	City	State
Argentina	Chutro Srl Clinic	Córdoba
Argentina	Del Prado Private Clinic	Córdoba
Argentina	San Roque Hospital	Córdoba
Argentina	Rosario Cardiovascular Institute	Rosario
Argentina	Rosario Clinical Research Institute - Delta	Rosario
Argentina	Modelo Cardiology Center	San Miguel De Tucumán
Argentina	Diagnostic and Treatment Medical Clinic SA	Santa Fe
Argentina	Santa Rosa Hospital	Santa Rosa
Argentina	San Martin SA Clinic	Venado Tuerto
Argentina	Fusavim Privada SRL Clinic	Villa María
Argentina	Sanatorio de la Canada	Villa María	Cordoba
Austria	Internal Med. 1, St. Josef Hospital Braunau	Braunau Am Inn
Austria	Clin. Dep. Internal Med 3, University Hospital St. Poelten	St. Poelten
Austria	Internal Med., LKH Villach	Villach
Austria	1. Med. Dep, Donauspital	Wien
Austria	Cardiology Department at Hietzing Hospital with Neurological Center Rosenhugel	Wien
Austria	Dep. Of Cardiology, Medical Univ. Vienna	Wien
Colombia	CEQUIN Cardiomet Foundation	Armenia	Quindio
Colombia	Santander Ophthalmological Foundation	Bucaramanga	Santander
Colombia	Cardiovascular Diagnostic Center	Cartagena	Bolivar
Colombia	Cardiomet Pereira Clinical Research Center Foundation	Pereira	Risaralda
France	Auxerre Hospital Center	Auxerre
France	University Hospital of Beziers	Béziers
France	Center Hospital Regional University of Tours Trousseu Hospital	Chambray-lès-Tours
France	University Hospital Henri Mondor	Creil
France	CHU Dijon Burgundy F. Mitterand	Dijon
France	Hôpitaux Universitaires Saint-Louis-Lariboisière, University Paris Diderot	Paris
France	Center Hospital of Toulon	Toulon
Hungary	Buda Hospital of the Hospitaller Order of Saint John of God	Budapest
Hungary	Kanizsai Dorottya Hospital	Nagykanizsa
Hungary	St. Rafael Hospital in Zala County	Zalaegerszeg
Israel	Barzilay MC Ashkelon	Ashkelon
Israel	Asaf Harofe MC	Zerifin
Mozambique	Dept of Medicine Research unit, Maputo Central Hospital	Maputo
Mozambique	Mavalane Hospital, National Institute of Health	Maputo
Nigeria	Amino Kano Teaching Hospital	Kano
Nigeria	Murtala Muhammad Specialist Hospital	Kano
Russian Federation	State Budget HealthCare Institution "First City clinical hospital named after E.E. Volosevich"	Arkhangel'sk
Russian Federation	Regional budget Healthcare Institution "Cardiological dispensary"	Ivanovo
Russian Federation	Federal State Budget Educational Institution of Higher Education "Moscow State Medico-Dental University n.a. A.I. Evdokimov", under Ministry of Health of the Russian Federation	Moscow
Russian Federation	Federal State Budget Educational Institution of Higher Education "Moscow State University n.a. M.V. Lomonosov", independent division Medical research Educational Centre	Moscow
Russian Federation	Moscow City Hospital # 81, Moscow	Moscow
Russian Federation	Moscow State Budget Healthcare Institution City clinical Hospital 52 of Moscow Healthcare Department	Moscow
Russian Federation	Primary Healthcare Unit of the RF Ministry of Internal Affairs in Moscow	Moscow
Russian Federation	Russian National Research Medical University n.a. N.I.Pirogov based at City Clinical hospital n.a. V.M.Buyanov DZM	Moscow
Russian Federation	SBHI of Moscow City clinical hospital 64 of Moscow Healthcare department	Moscow
Russian Federation	State Budget HealthCare Institution of Moscow "City clinical hospital 15 n.a. O.M. Filatov under Department of HealthCare of Moscow"	Moscow
Russian Federation	State Budget HealthCare Institution of Moscow "City clinical hospital 29 n.a. N.E. Bauman under Department of HealthCare of Moscow"	Moscow
Russian Federation	State Budget HealthCare Institution of Mosocw "City clinical hospital 51 under Department of HealthCare of Moscow"	Moscow
Russian Federation	Saint-Petersburg State Budget HealthCare Institution "City hospital 38 n.a. N.A. Semashko"	Pushkin
Russian Federation	Municipal Government-financed Institution of Healthcare "City Emergency Hospital" of Rostov-on-Don City	Rostov-on-Don
Russian Federation	Federal State Budgetary Educational Institution of Higher Education "Ryazan State Medical University named after academician I.P. Pavlov"	Ryazan'
Russian Federation	Federal State Budget Educational Institution of Higher Education "North-West state medical university n.a. I.I. Mechnikov under the Ministry of Health of the Russian Federation"	Saint Petersburg
Russian Federation	Saint Petersburg State Budget Healthcare Institution Pokrovskaya City Hospital	Saint Petersburg
Russian Federation	Saint-Petersburg State Budget Healthcare Institution City Hospital 15	Saint Petersburg
Russian Federation	State Budget Institution "Saint Petersburg state budget research institution of first aid named after I. I. Dzhanelidze"	Saint Petersburg
Russian Federation	State Budget HealthCare Institution of Vladimir Region "City Hospital 4 of Vladimir"	Vladimir
Russian Federation	State Institution of Healthcare of Yaroslavl Region "Clinical Hospital 8"	Yaroslavl
Slovakia	National Institute of Cardio and Vascular Diseases	Bratislava
Slovakia	V. Internal Clinic, LFUK and UNB Bratislava	Bratislava
Slovakia	Internal Department, Hospital with Polyclinic Brezno	Brezno
Slovakia	Internal Department, Dolnooravian Hospital of Dr. L.N.Jege	Dolný Kubín
Slovakia	Internal Department, Hospital with Polyclinic Lucenec	Lucenec
Slovakia	First Internal Clinic, Faculty Hospital with Polyclinic Nove Zamky	Nové Zámky
Slovakia	Department of Internal Medicine Hospital Rimavska Sobota	Rimavská Sobota
Slovakia	Department of Internal Medicine UVN SNP-FN	Ružomberok
Slovakia	Internal Department, NsP Spisska Nova Ves	Spišská Nová Ves
Slovakia	Internal Department Hospital Arm General L. Svobodu Svidnik	Svidník
South Africa	Groote Schuur Hospital	Cape Town
South Africa	Nelson Mandela Academic Hospital, Walter Sisulu University	Mthatha
Tunisia	Habib Bougatfa Hospital	Bizerte
Tunisia	Regional Hospital of Jendouba	Jendouba
Tunisia	Fattouma Bourguiba Hospital	Monastir
Tunisia	Hedi chaker Hospital	Sfax
Tunisia	Charles Nicolle Hospital	Tunis
Tunisia	Habib Thameur Hospital	Tunis
Tunisia	La Rabta Hospital	Tunis
Tunisia	Military Hospital	Tunis

Sponsors (5)

Lead Sponsor	Collaborator
Heart Initiative	Hôpitaux Universitaires Saint-Louis-Lariboisière, Inserm UMRS 942, Momentum Research, Inc., Roche Diagnostics

Countries where clinical trial is conducted

Argentina,  Austria,  Colombia,  France,  Hungary,  Israel,  Mozambique,  Nigeria,  Russian Federation,  Slovakia,  South Africa,  Tunisia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	180-day cardiovascular death	Cumulative risk of death due to cardiovascular cause at 180 days	180 days
Other	90-day cardiovascular death	Cumulative risk of death due to cardiovascular cause at 90 days	90 days
Other	90-day all-cause mortality	Cumulative risk of death at 90 days	90 days
Other	180-day heart failure readmission	Cumulative risk of readmission for heart failure at 180 days	180 days
Other	90-day heart failure readmission	Cumulative risk of readmission for heart failure at 90 days	90 days
Other	Finkelstein-Schoenfeld hierarchical composite	Hierarchical composite endpoint comprising death, heart failure readmissions, and EQ-VAS analyzed using Finkelstein-Schoenfeld methodology	90 days
Other	Change in NT-proBNP	Change from baseline to 90 days in NT-proBNP on the log scale	90 days
Other	Change in weight	Change from baseline to 90 days in weight in kg	90 days
Other	Changes in signs and symptoms of congestion: NYHA class	Changes from baseline to 90 days in New York Heart Association (NYHA) class which ranges from 1 to 4 with a higher class representing a worse outcome	90 days
Other	Changes in signs and symptoms of congestion: orthopnea	Changes from baseline to 90 days in orthopnea rated on a scale from 0 to 3 with a higher score representing a worse outcome	90 days
Other	Changes in signs and symptoms of congestion: peripheral edema	Changes from baseline to 90 days in peripheral edema rated on a scale from 0 to 3 with a higher score representing a worse outcome	90 days
Other	Changes in signs and symptoms of congestion: rales	Changes from baseline to 90 days in rales rated on a scale from 0 to 3 with a higher score representing a worse outcome	90 days
Other	Changes in signs and symptoms of congestion: JVP	Changes from baseline to 90 days in jugular venous pulse (JVP) rated on a scale from 1 to 4 with a higher score representing a worse outcome	90 days
Primary	180-day all-cause mortality or heart failure readmission	Cumulative risk of either readmission for heart failure or death at 180 days	180 days
Secondary	Change in quality of life	Change from baseline to 90 days in quality of life as measured using the EQ-5D visual analogue scale (VAS) which ranges from 0 to 100 with a higher score representing a better outcome. "EQ-5D" is the official name of a quality of life instrument developed by EuroQol.	90 days
Secondary	180-day all-cause mortality	Cumulative risk of death at 180 days	180 days
Secondary	90-day all-cause mortality or heart failure readmission	Cumulative risk of either readmission for heart failure or death at 90 days	90 days