CClinicalTrials.gg
Status unknownNCT03412201STRONG-HFUpdated Feb 12, 2021

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

An interventional study of Usual Care and High Intensity Care in Heart Failure, sponsored by Heart Initiative. Status unknown at 78 sites in 12 countries. Open to participants aged 18 Years to 85 Years. Per ClinicalTrials.gov, last updated 2021-02-12.

Sponsored by Heart Initiative · Not applicable, Interventional, and Treatment

The sponsor has not verified this record recently (last verified Feb 2021), so the status shown — last known as Recruiting — may be out of date.
Phase
Not applicable
Study type
Interventional
Enrollment
1,800
Allocation
Randomized
Ages
18 Years to 85 Years
Sex
All
01

Study 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.

Read the 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.

02

Conditions studied

  • Heart Failure

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Keywords

  • Disease management
  • Medication therapy management
  • Biomarkers
03

Who can participate

Ages eligible
18 Years to 85 Years
Sexes eligible
All
Accepts healthy volunteers
No

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

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.
04

Study design

Phase
Not applicable
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
1,800 participants (estimated)

Study arms

  • 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

  • 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

Interventions

  • OtherUsual Care

    Follow-up and management of heart failure medications provided by the patient's general physician and/or cardiologist according to local medical standards

  • OtherHigh 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.

05

What researchers measure

Primary outcomes

  1. 180-day all-cause mortality or heart failure readmission

    Cumulative risk of either readmission for heart failure or death at 180 days

    Time frame: 180 days

Secondary outcomes

  1. 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.

    Time frame: 90 days

  2. 180-day all-cause mortality

    Cumulative risk of death at 180 days

    Time frame: 180 days

  3. 90-day all-cause mortality or heart failure readmission

    Cumulative risk of either readmission for heart failure or death at 90 days

    Time frame: 90 days

Other outcomes

  1. 180-day cardiovascular death

    Cumulative risk of death due to cardiovascular cause at 180 days

    Time frame: 180 days

  2. 90-day cardiovascular death

    Cumulative risk of death due to cardiovascular cause at 90 days

    Time frame: 90 days

  3. 90-day all-cause mortality

    Cumulative risk of death at 90 days

    Time frame: 90 days

  4. 180-day heart failure readmission

    Cumulative risk of readmission for heart failure at 180 days

    Time frame: 180 days

  5. 90-day heart failure readmission

    Cumulative risk of readmission for heart failure at 90 days

    Time frame: 90 days

  6. Finkelstein-Schoenfeld hierarchical composite

    Hierarchical composite endpoint comprising death, heart failure readmissions, and EQ-VAS analyzed using Finkelstein-Schoenfeld methodology

    Time frame: 90 days

  7. Change in NT-proBNP

    Change from baseline to 90 days in NT-proBNP on the log scale

    Time frame: 90 days

  8. Change in weight

    Change from baseline to 90 days in weight in kg

    Time frame: 90 days

  9. 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

    Time frame: 90 days

  10. 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

    Time frame: 90 days

  11. 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

    Time frame: 90 days

  12. 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

    Time frame: 90 days

  13. 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

    Time frame: 90 days

06

Study locations

33 of 78 sites recruiting
  • Sanatorio de la Canada
    Villa María, Cordoba X5900JKA, Argentina
    Recruiting
  • Chutro Srl Clinic
    Córdoba, Argentina
    Recruiting
  • Del Prado Private Clinic
    Córdoba, Argentina
    Recruiting
  • San Roque Hospital
    Córdoba, Argentina
    Recruiting
  • Rosario Cardiovascular Institute
    Rosario, Argentina
    Recruiting
  • Rosario Clinical Research Institute - Delta
    Rosario, Argentina
    Recruiting
  • Modelo Cardiology Center
    San Miguel De Tucumán, Argentina
    Recruiting
  • Diagnostic and Treatment Medical Clinic SA
    Santa Fe, Argentina
    • Miguel Angel Hominal · Contact
    Recruiting
  • Santa Rosa Hospital
    Santa Rosa, Argentina
    Recruiting
  • San Martin SA Clinic
    Venado Tuerto, Argentina
    Recruiting
  • Fusavim Privada SRL Clinic
    Villa María, Argentina
    Recruiting
  • Internal Med. 1, St. Josef Hospital Braunau
    Braunau Am Inn, Austria
    Terminated
  • Clin. Dep. Internal Med 3, University Hospital St. Poelten
    St. Poelten, Austria
    Terminated
  • Internal Med., LKH Villach
    Villach, Austria
    Withdrawn
  • 1. Med. Dep, Donauspital
    Wien, Austria
    Withdrawn
  • Cardiology Department at Hietzing Hospital with Neurological Center Rosenhugel
    Wien, Austria
    Withdrawn
  • Dep. Of Cardiology, Medical Univ. Vienna
    Wien, Austria
    Withdrawn
  • Cardiovascular Diagnostic Center
    Cartagena, Bolivar 130001, Colombia
    • Fernando Gabriel Manzur Jattín · Contact · 3157315055
    Recruiting
  • CEQUIN Cardiomet Foundation
    Armenia, Quindio 630004, Colombia
    • Gregorio Sánchez Vallejo · Contact · 3104527096
    Recruiting
  • Cardiomet Pereira Clinical Research Center Foundation
    Pereira, Risaralda 660003, Colombia
    • Luis Hernando Garcia Ortiz · Contact · 3116111
    Recruiting
  • Santander Ophthalmological Foundation
    Bucaramanga, Santander 681004, Colombia
    • Juan Diego Higuera Cobos · Contact · 3162791839
    Recruiting
  • Auxerre Hospital Center
    Auxerre, France
    Withdrawn
  • University Hospital of Beziers
    Béziers, France
    Withdrawn
  • Center Hospital Regional University of Tours Trousseu Hospital
    Chambray-lès-Tours, France
    Withdrawn
  • University Hospital Henri Mondor
    Creil, France
    Withdrawn
  • CHU Dijon Burgundy F. Mitterand
    Dijon, France
    Withdrawn
  • Hôpitaux Universitaires Saint-Louis-Lariboisière, University Paris Diderot
    Paris, France
    Withdrawn
  • Center Hospital of Toulon
    Toulon, France
    Withdrawn
  • Buda Hospital of the Hospitaller Order of Saint John of God
    Budapest, Hungary
    Terminated
  • Kanizsai Dorottya Hospital
    Nagykanizsa, Hungary
    Terminated
  • St. Rafael Hospital in Zala County
    Zalaegerszeg, Hungary
    Withdrawn
  • Barzilay MC Ashkelon
    Ashkelon, Israel
    Terminated
  • Asaf Harofe MC
    Zerifin, Israel
    Withdrawn
  • Dept of Medicine Research unit, Maputo Central Hospital
    Maputo, Mozambique
    Recruiting
  • Mavalane Hospital, National Institute of Health
    Maputo, Mozambique
    Terminated
  • Amino Kano Teaching Hospital
    Kano, Nigeria
    Recruiting
  • Murtala Muhammad Specialist Hospital
    Kano, Nigeria
    Recruiting
  • State Budget HealthCare Institution "First City clinical hospital named after E.E. Volosevich"
    Arkhangel'sk, Russian Federation
    Recruiting
  • Regional budget Healthcare Institution "Cardiological dispensary"
    Ivanovo, Russian Federation
    Recruiting
  • 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
    Recruiting
  • 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
    Terminated
  • Moscow City Hospital # 81, Moscow
    Moscow, Russian Federation
    Recruiting
  • Moscow State Budget Healthcare Institution City clinical Hospital 52 of Moscow Healthcare Department
    Moscow, Russian Federation
    Recruiting
  • Primary Healthcare Unit of the RF Ministry of Internal Affairs in Moscow
    Moscow, Russian Federation
    Terminated
  • Russian National Research Medical University n.a. N.I.Pirogov based at City Clinical hospital n.a. V.M.Buyanov DZM
    Moscow, Russian Federation
    Recruiting
  • SBHI of Moscow City clinical hospital 64 of Moscow Healthcare department
    Moscow, Russian Federation
    Recruiting
  • State Budget HealthCare Institution of Moscow "City clinical hospital 15 n.a. O.M. Filatov under Department of HealthCare of Moscow"
    Moscow, Russian Federation
    Recruiting
  • State Budget HealthCare Institution of Moscow "City clinical hospital 29 n.a. N.E. Bauman under Department of HealthCare of Moscow"
    Moscow, Russian Federation
    Recruiting
  • State Budget HealthCare Institution of Mosocw "City clinical hospital 51 under Department of HealthCare of Moscow"
    Moscow, Russian Federation
    Recruiting
  • Saint-Petersburg State Budget HealthCare Institution "City hospital 38 n.a. N.A. Semashko"
    Pushkin, Russian Federation
    Terminated
  • Municipal Government-financed Institution of Healthcare "City Emergency Hospital" of Rostov-on-Don City
    Rostov-on-Don, Russian Federation
    Recruiting
  • Federal State Budgetary Educational Institution of Higher Education "Ryazan State Medical University named after academician I.P. Pavlov"
    Ryazan', Russian Federation
    Recruiting
  • 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
    Terminated
  • Saint Petersburg State Budget Healthcare Institution Pokrovskaya City Hospital
    Saint Petersburg, Russian Federation
    Terminated
  • Saint-Petersburg State Budget Healthcare Institution City Hospital 15
    Saint Petersburg, Russian Federation
    Recruiting
  • State Budget Institution "Saint Petersburg state budget research institution of first aid named after I. I. Dzhanelidze"
    Saint Petersburg, Russian Federation
    Recruiting
  • State Budget HealthCare Institution of Vladimir Region "City Hospital 4 of Vladimir"
    Vladimir, Russian Federation
    Recruiting
  • State Institution of Healthcare of Yaroslavl Region "Clinical Hospital 8"
    Yaroslavl, Russian Federation
    Terminated
  • National Institute of Cardio and Vascular Diseases
    Bratislava, Slovakia
    Terminated
  • V. Internal Clinic, LFUK and UNB Bratislava
    Bratislava, Slovakia
    Terminated
  • Internal Department, Hospital with Polyclinic Brezno
    Brezno, Slovakia
    Terminated
  • Internal Department, Dolnooravian Hospital of Dr. L.N.Jege
    Dolný Kubín, Slovakia
    Terminated
  • Internal Department, Hospital with Polyclinic Lucenec
    Lučenec, Slovakia
    Terminated
  • First Internal Clinic, Faculty Hospital with Polyclinic Nove Zamky
    Nové Zámky, Slovakia
    Terminated
  • Department of Internal Medicine Hospital Rimavska Sobota
    Rimavská Sobota, Slovakia
    Terminated
  • Department of Internal Medicine UVN SNP-FN
    Ružomberok, Slovakia
    Terminated
  • Internal Department, NsP Spisska Nova Ves
    Spišská Nová Ves, Slovakia
    Terminated
  • Internal Department Hospital Arm General L. Svobodu Svidnik
    Svidník, Slovakia
    Terminated
  • Groote Schuur Hospital
    Cape Town, South Africa
    Terminated
  • Nelson Mandela Academic Hospital, Walter Sisulu University
    Mthatha, South Africa
    Terminated
  • Habib Bougatfa Hospital
    Bizerte, Tunisia
    Terminated
  • Regional Hospital of Jendouba
    Jendouba, Tunisia
    Terminated
  • Fattouma Bourguiba Hospital
    Monastir, Tunisia
    Terminated
  • Hedi chaker Hospital
    Sfax, Tunisia
    Terminated
  • Charles Nicolle Hospital
    Tunis, Tunisia
    Withdrawn
  • Habib Thameur Hospital
    Tunis, Tunisia
    Terminated
  • La Rabta Hospital
    Tunis, Tunisia
    Terminated
  • Military Hospital
    Tunis, Tunisia
    Withdrawn
07

References and documents

Publications

  • Mebazaa A, Davison B, Chioncel O, Cohen-Solal A, Diaz R, Filippatos G, Metra M, Ponikowski P, Sliwa K, Voors AA, Edwards C, Novosadova M, Takagi K, Damasceno A, Saidu H, Gayat E, Pang PS, Celutkiene J, Cotter G. Safety, tolerability and efficacy of up-titration of guideline-directed medical therapies for acute heart failure (STRONG-HF): a multinational, open-label, randomised, trial. Lancet. 2022 Dec 3;400(10367):1938-1952. doi: 10.1016/S0140-6736(22)02076-1. Epub 2022 Nov 7. PubMed 36356631 ↗
  • Cotter G, Davison B, Metra M, Sliwa K, Voors AA, Addad F, Celutkiene J, Chioncel O, Cohen Solal A, Diaz R, Damasceno A, Duengen HD, Filippatos G, Goncalvesova E, Merai I, Ponikowski P, Privalov D, Sani MU, Takagi K, Shogenov Z, Saidu H, Mebazaa A. Amended STRONG-HF study design. Eur J Heart Fail. 2021 Nov;23(11):1981-1982. doi: 10.1002/ejhf.2348. Epub 2021 Oct 4. No abstract available. PubMed 34529313 ↗
  • Kimmoun A, Cotter G, Davison B, Takagi K, Addad F, Celutkiene J, Chioncel O, Solal AC, Diaz R, Damasceno A, Duengen HD, Filippatos G, Goncalvesova E, Merai I, Metra M, Ponikowski P, Privalov D, Sliwa K, Sani MU, Voors AA, Shogenov Z, Mebazaa A. Safety, Tolerability and efficacy of Rapid Optimization, helped by NT-proBNP and GDF-15, of Heart Failure therapies (STRONG-HF): rationale and design for a multicentre, randomized, parallel-group study. Eur J Heart Fail. 2019 Nov;21(11):1459-1467. doi: 10.1002/ejhf.1575. Epub 2019 Aug 19. PubMed 31423712 ↗

Individual participant data

Plan to share: Undecided

08

Registry details

Key details

Study ID
NCT03412201
Lead sponsor
Heart Initiative
Collaborators
Hôpitaux Universitaires Saint-Louis-Lariboisière, Momentum Research, Inc., Roche Diagnostics GmbH, Inserm UMRS 942
Responsible party
Sponsor
First posted
Jan 26, 2018
Start date
May 11, 2018
Primary completion
Oct 2021 (estimated)
Completion
Oct 2021 (estimated)
Last update
Feb 12, 2021

Study contacts

Maria Novosadova, MD
Contact
marianovosadova@momentum-research.com
+41614851250
Alexandre Mebazaa, MD PhD FESC
principal investigator · Inserm UMRS 942; Hôpitaux Universitaires Saint-Louis-Lariboisière, University Paris Diderot

Oversight

Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
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