STRONG-HF: Safety, Tolerability and Efficacy of Rapid Optimization, Helped by NT-proBNP testinG, of Heart Failure Therapies
Study Details
Study Description
Brief 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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
N/A |
Detailed 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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: 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 |
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
|
| Experimental: 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. |
Other: 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.
|
Outcome Measures
Primary Outcome Measures
- 180-day all-cause mortality or heart failure readmission [180 days]
Cumulative risk of either readmission for heart failure or death at 180 days
Secondary Outcome Measures
- Change in quality of life [90 days]
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.
- 180-day all-cause mortality [180 days]
Cumulative risk of death at 180 days
- 90-day all-cause mortality or heart failure readmission [90 days]
Cumulative risk of either readmission for heart failure or death at 90 days
Other Outcome Measures
- 180-day cardiovascular death [180 days]
Cumulative risk of death due to cardiovascular cause at 180 days
- 90-day cardiovascular death [90 days]
Cumulative risk of death due to cardiovascular cause at 90 days
- 90-day all-cause mortality [90 days]
Cumulative risk of death at 90 days
- 180-day heart failure readmission [180 days]
Cumulative risk of readmission for heart failure at 180 days
- 90-day heart failure readmission [90 days]
Cumulative risk of readmission for heart failure at 90 days
- Finkelstein-Schoenfeld hierarchical composite [90 days]
Hierarchical composite endpoint comprising death, heart failure readmissions, and EQ-VAS analyzed using Finkelstein-Schoenfeld methodology
- Change in NT-proBNP [90 days]
Change from baseline to 90 days in NT-proBNP on the log scale
- Change in weight [90 days]
Change from baseline to 90 days in weight in kg
- Changes in signs and symptoms of congestion: NYHA class [90 days]
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
- Changes in signs and symptoms of congestion: orthopnea [90 days]
Changes from baseline to 90 days in orthopnea rated on a scale from 0 to 3 with a higher score representing a worse outcome
- Changes in signs and symptoms of congestion: peripheral edema [90 days]
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
- Changes in signs and symptoms of congestion: rales [90 days]
Changes from baseline to 90 days in rales rated on a scale from 0 to 3 with a higher score representing a worse outcome
- Changes in signs and symptoms of congestion: JVP [90 days]
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
Eligibility Criteria
Criteria
Inclusion Criteria:
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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.
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All measures within 24 hours prior to Randomization of systolic blood pressure ≥ 100 mmHg, and of heart rate ≥ 60 bpm.
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All measures within 24 hours prior to Randomization of serum potassium ≤ 5.0 mEq/L (mmol/L).
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Biomarker criteria for persistent congestion:
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At Screening, NT-proBNP > 2,500 pg/mL.
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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).
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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.
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Written informed consent to participate in the study.
Exclusion Criteria:
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Age < 18 or > 85 years.
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Clearly documented intolerance to high doses of beta-blockers.
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Clearly documented intolerance to high doses of renin-angiotensin system (RAS) blockers (both ACEi and ARB).
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Mechanical ventilation [not including continuous positive airway pressure (CPAP)/bilevel positive airway pressure (BIPAP)] in the 24 hours prior to Screening.
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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.
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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.
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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.
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Uncorrected thyroid disease, active myocarditis, or known amyloid or hypertrophic obstructive cardiomyopathy.
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History of heart transplant or on a transplant list, or using or planned to be implanted with a ventricular assist device.
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Sustained ventricular arrhythmia with syncopal episodes within the 3 months prior to screening that is untreated.
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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.
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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.
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Stroke or transient ischemic attack (TIA) within the 3 months prior to Screening.
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Primary liver disease considered to be life threatening.
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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.
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Psychiatric or neurological disorder, cirrhosis, or active malignancy leading to a life expectancy < 6 months.
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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
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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.
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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
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Pregnant or nursing (lactating) women.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Sanatorio de la Canada | Villa María | Cordoba | Argentina | X5900JKA |
| 2 | Chutro Srl Clinic | Córdoba | Argentina | ||
| 3 | Del Prado Private Clinic | Córdoba | Argentina | ||
| 4 | San Roque Hospital | Córdoba | Argentina | ||
| 5 | Rosario Cardiovascular Institute | Rosario | Argentina | ||
| 6 | Rosario Clinical Research Institute - Delta | Rosario | Argentina | ||
| 7 | Modelo Cardiology Center | San Miguel De Tucumán | Argentina | ||
| 8 | Diagnostic and Treatment Medical Clinic SA | Santa Fe | Argentina | ||
| 9 | Santa Rosa Hospital | Santa Rosa | Argentina | ||
| 10 | San Martin SA Clinic | Venado Tuerto | Argentina | ||
| 11 | Fusavim Privada SRL Clinic | Villa María | Argentina | ||
| 12 | Internal Med. 1, St. Josef Hospital Braunau | Braunau Am Inn | Austria | ||
| 13 | Clin. Dep. Internal Med 3, University Hospital St. Poelten | St. Poelten | Austria | ||
| 14 | Internal Med., LKH Villach | Villach | Austria | ||
| 15 | 1. Med. Dep, Donauspital | Wien | Austria | ||
| 16 | Cardiology Department at Hietzing Hospital with Neurological Center Rosenhugel | Wien | Austria | ||
| 17 | Dep. Of Cardiology, Medical Univ. Vienna | Wien | Austria | ||
| 18 | Cardiovascular Diagnostic Center | Cartagena | Bolivar | Colombia | 130001 |
| 19 | CEQUIN Cardiomet Foundation | Armenia | Quindio | Colombia | 630004 |
| 20 | Cardiomet Pereira Clinical Research Center Foundation | Pereira | Risaralda | Colombia | 660003 |
| 21 | Santander Ophthalmological Foundation | Bucaramanga | Santander | Colombia | 681004 |
| 22 | Auxerre Hospital Center | Auxerre | France | ||
| 23 | University Hospital of Beziers | Béziers | France | ||
| 24 | Center Hospital Regional University of Tours Trousseu Hospital | Chambray-lès-Tours | France | ||
| 25 | University Hospital Henri Mondor | Creil | France | ||
| 26 | CHU Dijon Burgundy F. Mitterand | Dijon | France | ||
| 27 | Hôpitaux Universitaires Saint-Louis-Lariboisière, University Paris Diderot | Paris | France | ||
| 28 | Center Hospital of Toulon | Toulon | France | ||
| 29 | Buda Hospital of the Hospitaller Order of Saint John of God | Budapest | Hungary | ||
| 30 | Kanizsai Dorottya Hospital | Nagykanizsa | Hungary | ||
| 31 | St. Rafael Hospital in Zala County | Zalaegerszeg | Hungary | ||
| 32 | Barzilay MC Ashkelon | Ashkelon | Israel | ||
| 33 | Asaf Harofe MC | Zerifin | Israel | ||
| 34 | Dept of Medicine Research unit, Maputo Central Hospital | Maputo | Mozambique | ||
| 35 | Mavalane Hospital, National Institute of Health | Maputo | Mozambique | ||
| 36 | Amino Kano Teaching Hospital | Kano | Nigeria | ||
| 37 | Murtala Muhammad Specialist Hospital | Kano | Nigeria | ||
| 38 | State Budget HealthCare Institution "First City clinical hospital named after E.E. Volosevich" | Arkhangel'sk | Russian Federation | ||
| 39 | Regional budget Healthcare Institution "Cardiological dispensary" | Ivanovo | Russian Federation | ||
| 40 | 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 | ||
| 41 | 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 | ||
| 42 | Moscow City Hospital # 81, Moscow | Moscow | Russian Federation | ||
| 43 | Moscow State Budget Healthcare Institution City clinical Hospital 52 of Moscow Healthcare Department | Moscow | Russian Federation | ||
| 44 | Primary Healthcare Unit of the RF Ministry of Internal Affairs in Moscow | Moscow | Russian Federation | ||
| 45 | Russian National Research Medical University n.a. N.I.Pirogov based at City Clinical hospital n.a. V.M.Buyanov DZM | Moscow | Russian Federation | ||
| 46 | SBHI of Moscow City clinical hospital 64 of Moscow Healthcare department | Moscow | Russian Federation | ||
| 47 | State Budget HealthCare Institution of Moscow "City clinical hospital 15 n.a. O.M. Filatov under Department of HealthCare of Moscow" | Moscow | Russian Federation | ||
| 48 | State Budget HealthCare Institution of Moscow "City clinical hospital 29 n.a. N.E. Bauman under Department of HealthCare of Moscow" | Moscow | Russian Federation | ||
| 49 | State Budget HealthCare Institution of Mosocw "City clinical hospital 51 under Department of HealthCare of Moscow" | Moscow | Russian Federation | ||
| 50 | Saint-Petersburg State Budget HealthCare Institution "City hospital 38 n.a. N.A. Semashko" | Pushkin | Russian Federation | ||
| 51 | Municipal Government-financed Institution of Healthcare "City Emergency Hospital" of Rostov-on-Don City | Rostov-on-Don | Russian Federation | ||
| 52 | Federal State Budgetary Educational Institution of Higher Education "Ryazan State Medical University named after academician I.P. Pavlov" | Ryazan' | Russian Federation | ||
| 53 | 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 | ||
| 54 | Saint Petersburg State Budget Healthcare Institution Pokrovskaya City Hospital | Saint Petersburg | Russian Federation | ||
| 55 | Saint-Petersburg State Budget Healthcare Institution City Hospital 15 | Saint Petersburg | Russian Federation | ||
| 56 | State Budget Institution "Saint Petersburg state budget research institution of first aid named after I. I. Dzhanelidze" | Saint Petersburg | Russian Federation | ||
| 57 | State Budget HealthCare Institution of Vladimir Region "City Hospital 4 of Vladimir" | Vladimir | Russian Federation | ||
| 58 | State Institution of Healthcare of Yaroslavl Region "Clinical Hospital 8" | Yaroslavl | Russian Federation | ||
| 59 | National Institute of Cardio and Vascular Diseases | Bratislava | Slovakia | ||
| 60 | V. Internal Clinic, LFUK and UNB Bratislava | Bratislava | Slovakia | ||
| 61 | Internal Department, Hospital with Polyclinic Brezno | Brezno | Slovakia | ||
| 62 | Internal Department, Dolnooravian Hospital of Dr. L.N.Jege | Dolný Kubín | Slovakia | ||
| 63 | Internal Department, Hospital with Polyclinic Lucenec | Lučenec | Slovakia | ||
| 64 | First Internal Clinic, Faculty Hospital with Polyclinic Nove Zamky | Nové Zámky | Slovakia | ||
| 65 | Department of Internal Medicine Hospital Rimavska Sobota | Rimavská Sobota | Slovakia | ||
| 66 | Department of Internal Medicine UVN SNP-FN | Ružomberok | Slovakia | ||
| 67 | Internal Department, NsP Spisska Nova Ves | Spišská Nová Ves | Slovakia | ||
| 68 | Internal Department Hospital Arm General L. Svobodu Svidnik | Svidník | Slovakia | ||
| 69 | Groote Schuur Hospital | Cape Town | South Africa | ||
| 70 | Nelson Mandela Academic Hospital, Walter Sisulu University | Mthatha | South Africa | ||
| 71 | Habib Bougatfa Hospital | Bizerte | Tunisia | ||
| 72 | Regional Hospital of Jendouba | Jendouba | Tunisia | ||
| 73 | Fattouma Bourguiba Hospital | Monastir | Tunisia | ||
| 74 | Hedi chaker Hospital | Sfax | Tunisia | ||
| 75 | Charles Nicolle Hospital | Tunis | Tunisia | ||
| 76 | Habib Thameur Hospital | Tunis | Tunisia | ||
| 77 | La Rabta Hospital | Tunis | Tunisia | ||
| 78 | Military Hospital | Tunis | Tunisia |
Sponsors and Collaborators
- Heart Initiative
- Hôpitaux Universitaires Saint-Louis-Lariboisière
- Momentum Research, Inc.
- Roche Diagnostics
- Inserm UMRS 942
Investigators
- Principal Investigator: Alexandre Mebazaa, MD PhD FESC, Inserm UMRS 942; Hôpitaux Universitaires Saint-Louis-Lariboisière, University Paris Diderot
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- CHF201701