Heart FailurePhase 4PopS-HFNCT07295522
Pharmacological Optimization in Prevention in Heart Failure: A Sex-gap?
A Phase 4 study testing Guideline-Directed Medical Therapy (GDMT) in people with Heart Failure and Acute Heart Failure, run by IRCCS Policlinico S. Donato at 12 sites in Italy.
Trial summary
The goal of this clinical trial is to learn whether a rapid and intensive optimization of heart failure medications in women can improve outcomes after hospitalization for heart failure. It will also investigate the safety and the tolerance of these treatments when given at full guideline-recommended doses. Read more about this study
- Who is it for?
- Ages 18 to 85 years, women only
- Conditions the study is for
- Heart Failure, Acute Heart Failure, Heart Failure With Reduced Ejection Fraction (HFrEF)
- What is being tested?
- Guideline-Directed Medical Therapy (GDMT)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 368 participants
- Where
- 12 sitesItaly
- Study dates
- 31 Mar 2026to 8 Jun 2028
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 85 years
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Female patients >18 <85 years.
- 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.
- All measures within 24 hours prior to Randomization of systolic blood pressure ≥ 100 mmHg, and of heart rate ≥ 60 bpm.
- All measures within 24 hours prior to Randomization of serum potassium ≤ 5.0 mEq/L (mmol/L).
- Biomarker criteria for persistent congestion:
- 5.1. At Screening, NT-proBNP >1,800 pg/mL (2,350 pg/mL in case of atrial fibrillation) 5.2. At the time of Randomization (1-2 days prior to discharge), NT-proBNP >1,000 pg/mL (1,300 pg/mL in case of Atrial Fibrillation) to ensure the persistence of congestion and the acuity of the index episode).
- At 1 week prior to admission, at Screening, and at Visit 2 6.1. If EF<50% (ie HFrEF or HFmrEF) either <½ the optimal dose of ACEi/ARB/ARNi and MRA and BB or no SGLT2i (see Table) must have been prescribed 6.2. If EF>50% (ie HFpEF): <½ the optimal dose of MRA (see Table) or no SGLT2i.
- Written informed consent to participate in the study.
Who cannot join
- Male patients
- Age < 18 or > 85 years.
- Mechanical ventilation (not including CPAP/BIPAP) in the 24 hours prior to Screening.
- Significant pulmonary disease contributing substantially to the patients' dyspnoea such as 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.
- 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 or during the index event.
- Index Event (admission for Acute Heart Failure) triggered primarily by a correctable aetiology 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 anaemia, 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.
- History of heart transplant or on a transplant list or using or planned to be implanted with a ventricular assist device.
- Sustained ventricular arrhythmia with syncopal episodes within the 3 months prior to screening that is untreated.
- 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
- Active infection at any time during the AHF hospitalization prior to Randomization based on abnormal temperature and elevated WBC or need for intravenous antibiotics.
- Stroke or Transient Ischemic Attack (TIA) within the 3 months prior to Screening.
- Primary liver disease considered to be life threatening.
- Renal disease or eGFR < 30 mL/min/1.73m2 (as estimated by the simplified MDRD formula) at Screening or history of dialysis.
- Psychiatric or neurological disorder, cirrhosis, or active malignancy leading to a life expectancy < 6 months.
- Prior (defined as less than 30 days from screening) or current enrollment in a CHF trial or participation in an investigational drug or device study within the 30 days prior to screening or 5 half-lives of the study drug, whichever is longer.
- 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 at 1-2 days prior to anticipated discharge.
- 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.
- Pregnant or nursing (lactating) women.
- Hypersensitivity to the active substance or to any of the excipients as indicated in Summary of Product Characteristics of Investigational Medicinal Product (IMPs).
- Angioedema.
- Severe heart failure (NYHA class IV).
Trial locations and contacts
12 sites in 1 country. Contact the study team or a site near you to ask about taking part.
12 sites in 1 country
Italy12 sites, 12 recruiting
- Not yet recruiting
Azienda Ospedaliero Universitaria Delle Marche
Ancona
- Not yet recruiting
Azienda USL Toscana Nord Ovest - Cecina
Cecina
- Not yet recruiting
Ospedale Universitario di Ferrara
Ferrara
- Not yet recruiting
Azienda USL Toscana Centro
Florence
- Not yet recruiting
Centro Cardiologico Monzino
Milan
- Not yet recruiting
Istituto Auxologico Italiano
Milan
- Not yet recruiting
Fondazione Toscana Gabriele Monasterio
Pisa
- Not yet recruiting
Ospedale S. Maria delle Croci
Ravenna
- Not yet recruiting
Azienda USL IRCCS Di Reggio Emilia
Reggio Emilia
- Not yet recruiting
Fondazione Policlinico Universitario Campus Bio-medico
Roma
- Not yet recruiting
Ospedale San Camillo Forlanini
Roma
- Recruiting
IRCCS Policlinico San Donato
San Donato Milanese, MILANO, 20097
Massimo Piepoli, MD, 0252774966, massimo.piepoli@grupposandonato.it
Giovanna Landi, PharmD, 0252774885, giovanna.landi@grupposandonato.it
About this study
The goal of this clinical trial is to learn whether a rapid and intensive optimization of heart failure medications in women can improve outcomes after hospitalization for heart failure. It will also investigate the safety and the tolerance of these treatments when given at full guideline-recommended doses.
The main questions it aims to answer are:
Read more
- Does intensive medication optimization reduce death or hospital readmissions for heart failure within one year?
- Do women benefit as much as men from intensive and full-dose heart failure therapy?
- Is this treatment protocol safe and feasible also in women?
Researchers will compare two groups of women hospitalized for heart failure:
- High-intensity care: starting and increasing all recommended heart-failure medications as quickly as possible and monitoring patients closely during the first weeks after discharge.
- Usual care: medications are started and adjusted gradually, according to the judgment of the treating cardiologist and the patient's usual care team.
The study will follow participants for 12 months to see whether the high-intensity strategy reduces death, hospital readmission for heart failure, or worsening symptoms. It will also evaluate side effects, medication tolerance, and quality of life.
Participants will be randomly assigned to one of the two groups, attend regular follow-up visits for one year, complete a short quality-of-life questionnaire (EQ-5D).
This study will include about 360 women from 13 hospitals in Italy. It is sponsored by IRCCS Policlinico San Donato and funded by the Italian Medicines Agency (AIFA).
Read the detailed description
PopS-HF is a phase IV, low-interventional, multicenter randomized controlled trial designed to test whether intensive optimization of guideline directed medical therapy (GDMT), following the STRONG-HF (Safety, Tolerability and Efficacy of Rapid Optimization, Helped by NT-proBNP Testing of Heart Failure Therapies) titration strategy, improves outcomes in women hospitalized for heart failure (HF).
The study also includes a retrospective analysis of national healthcare databases and specialized HF registries from 2018-2023 to evaluate how GDMT are prescribed in real-world practice and to identify sex-related differences in treatment patterns and outcomes.
Eligible patients are women aged 18-85 years hospitalized for acute HF with evidence of congestion and hemodynamic stability before discharge. Exclusion criteria include severe comorbidities, pregnancy, and inability to follow up.
The prospective component randomizes 368 patients to an intensive strategy or usual care, with follow-up visits at 2, 4, 6, 12, 24, 36, and 52 weeks.
The primary endpoint is a composite of all-cause mortality, HF readmission, or worsening HF within 1 year.
Secondary endpoints assess optimization of therapy, side effects, biomarkers (NT-proBNP), and quality of life.
- Conditions
- Heart Failure, Acute Heart Failure, Heart Failure With Reduced Ejection Fraction (HFrEF), Heart Failure With Preserved Ejection Fraction (HFPEF), Heart Failure With Mildly Reduced Ejection Fraction
- Being tested
- Guideline-Directed Medical Therapy (GDMT)
- Keywords
- heart failure, women, GDMT, Pharmacological Optimization, phase IV, High intensity up-titration, Secondary prevention, Sex differences, Real world data
- Medical subject headings
- Heart Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Guideline-Directed Medical Therapy (GDMT)Drug
Guideline-directed medical therapy (GDMT) including beta-blockers, ACE inhibitors or ARBs or ARNIs, mineralocorticoid receptor antagonists, and SGLT2 inhibitors, all approved and commercially available, used according to current ESC guidelines.
Participants in the high-intensity care arm are assigned to a strategy of rapid initiation and optimization of GDMT based on the STRONG-HF protocol. Eligible therapies (beta-blockers, ACEi/ARB/ARNI, mineralocorticoid receptor antagonists, and SGLT2 inhibitors for HFrEF/HFmrEF; MRA and SGLT2 inhibitors for HFpEF) are started during hospitalization at least at half of the recommended target dose, followed by frequent clinical assessments and dose titration, when clinically appropriate, within 6 weeks. Safety monitoring includes clinical examination, vital signs, laboratory tests (NT-proBNP, electrolytes, kidney function), and additional visits after each titration if needed.
| Study group | Role | What they receive |
|---|---|---|
| Usual care | No intervention | Participants in the usual care arm will receive sequential introduction and adjustment of guideline-directed medical therapy (GDMT) according to the treating cardiologist or general physician's clinical judgment, following routine practice. Follow-up will occur at weeks 6, 12, 24, 36, and 52 after randomization, with clinical visits and intermediate phone contacts as per standard care. |
| High-intensity care | Experimental | Participants assigned to the high-intensity arm will begin rapid initiation and optimization of guideline-directed medical therapy (GDMT) according to the STRONG-HF protocol. During hospitalization, eligible therapies (beta-blockers (BB), Angiotensin converting enzyme inhibitor(ACEi) /Angiotensin II receptor blocker (ARB)/Angiotensin Receptor-Neprilysin Inhibitors(ARNI), Mineralocorticoid Receptor Antagonists (MRA), and Sodium-Glucose Co-Transporter inhibitor 2 (SGLT2i) for HFrEF/HFmrEF; MRA and SGLT2i for HFpEF will be prescribed at least at half of the recommended target dose. Further titration toward full optimal doses will be performed within the first 6 weeks if clinically appropriate. Participants will undergo clinical assessments at weeks 2, 4, 6, 12, 24, 36, and 52, with safety monitoring including vital signs, physical examination, and laboratory evaluation (NT-proBNP, electrolytes, kidney function). Additional visits may occur after any up-titration if needed for safety. Receives: Drug: Guideline-Directed Medical Therapy (GDMT) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Composite of all-cause mortality, heart failure (HF) readmission, or worsening HF within 1 year.
Composite endpoint including occurrence of (1) death from any cause, (2) hospital readmission for heart failure, or (3) clinically assessed worsening of heart failure.
Measured: 12 months
Secondary outcomes (10)
Optimization of Beta-blocker Therapy
Percentage of participants achieving dose optimization of beta-blockers according to guideline-recommended targets or maximum tolerated dose.
Measured: 12 months
Optimization of ACEi/ARB/ARNI Therapy
Proportion of participants achieving dose optimization of ACE inhibitors, angiotensin receptor blockers, or angiotensin receptor-neprilysin inhibitors according to guideline-recommended targets or maximum tolerated dose.
Measured: 12 months
Optimization of Mineralocorticoid Receptor Antagonists (MRAs)
percentage of participants achieving dose optimization of MRAs at recommended dose or maximum tolerated dose.
Measured: 12 months
Optimization of SGLT2 Inhibitors
Percentage of poulation achieving full implementation of SGLT2 inhibitors
Measured: 12 months
Discontinuation of GDMT due to side effects
Percentage of participants discontinuing any GDMT class (beta-blockers, ACEi/ARB/ARNI for EF <50%, MRAs, or SGLT2 inhibitors) due to adverse effects or intolerance.
Measured: 12 months
NT-proBNP Changes
Change in plasma NT-proBNP levels from baseline to follow-up visits in each study arm.
Measured: 12 months
Quality of Life (EQ-5D-5L Score)
Change in health-related quality of life measured by the EuroQol 5-Dimension 5-Level (EQ-5D-5L) questionnaire. The EQ-5D-5L also includes a visual analogue scale (VAS) ranging from 0 to 100, with higher scores indicating better perceived health status.
Measured: 12 months
One-year All-Cause Mortality
Incidence of death from any cause within 12 months after randomization.
Measured: 12 months
One-year Heart Failure Readmission
Incidence of hospital readmission for heart failure within 12 months after randomization.
Measured: 12 months
One-year Worsening Heart Failure
Incidence of worsening heart failure within 12 months after randomization, defined as deterioration of heart failure signs and symptoms requiring urgent escalation of therapy, including emergency department visit or outpatient intravenous diuretic therapy.
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Dec 2025
- Study start31 Mar 2026
- Primary completion8 Jun 2027 (estimated)
- Study completion8 Jun 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (12)Papers the sponsor has linked to this study.
- Other trials for Heart FailureStudies of the same condition, open and under way.
- More trials run by IRCCS Policlinico S. DonatoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- A parallel-group design is used, with participants randomized 1:1 to receive either high-intensity optimization of guideline-directed medical therapy or usual care.
- Masking
- None (open label)
- Enrolment
- 368 participants (estimated)
Sponsor and investigators
- Lead sponsor
- IRCCS Policlinico S. Donato
- Sponsor type
- University, hospital or other
- Collaborators
- Agenzia Italiana del Farmaco
- Responsible party
- Principal investigator, Massimo Piepoli, IRCCS Policlinico S. Donato
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07295522
- Sponsor's protocol ID
- PopS-HF
- Other IDs
- 2025-520660-18, 2025
- Acronym
- PopS-HF
- Status last verified
- Mar 2026
- First submitted
- 1 Dec 2025
- Last updated
- 16 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: De-identified individual participant data (IPD) will not be made publicly available. Data sharing is restricted due to ethical and regulatory requirements under GDPR and Italian data protection regulations. Aggregate study results will be published.
Publications
Okumura N, Jhund PS, Gong J, Lefkowitz MP, Rizkala AR, Rouleau JL, Shi VC, Swedberg K, Zile MR, Solomon SD, Packer M, McMurray JJ; PARADIGM-HF Investigators and Committees*. Importance of Clinical Worsening of Heart Failure Treated in the Outpatient Setting: Evidence From the Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure Trial (PARADIGM-HF). Circulation. 2016 Jun 7;133(23):2254-62. doi: 10.1161/CIRCULATIONAHA.115.020729. Epub 2016 Apr 20.
PubMed 27143684Brotons C, Falces C, Alegre J, Ballarin E, Casanovas J, Cata T, Martinez M, Moral I, Ortiz J, Perez E, Rayo E, Recio J, Roig E, Vidal X. Randomized clinical trial of the effectiveness of a home-based intervention in patients with heart failure: the IC-DOM study. Rev Esp Cardiol. 2009 Apr;62(4):400-8. doi: 10.1016/s1885-5857(09)71667-6. English, Spanish.
PubMed 19401125Mebazaa 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 36356631Dewan P, Rorth R, Jhund PS, Shen L, Raparelli V, Petrie MC, Abraham WT, Desai AS, Dickstein K, Kober L, Mogensen UM, Packer M, Rouleau JL, Solomon SD, Swedberg K, Zile MR, McMurray JJV. Differential Impact of Heart Failure With Reduced Ejection Fraction on Men and Women. J Am Coll Cardiol. 2019 Jan 8;73(1):29-40. doi: 10.1016/j.jacc.2018.09.081.
PubMed 30621948Lainscak M, Milinkovic I, Polovina M, Crespo-Leiro MG, Lund LH, Anker SD, Laroche C, Ferrari R, Coats AJS, McDonagh T, Filippatos G, Maggioni AP, Piepoli MF, Rosano GMC, Ruschitzka F, Simic D, Asanin M, Eicher JC, Yilmaz MB, Seferovic PM; European Society of Cardiology Heart Failure Long-Term Registry Investigators Group. Sex- and age-related differences in the management and outcomes of chronic heart failure: an analysis of patients from the ESC HFA EORP Heart Failure Long-Term Registry. Eur J Heart Fail. 2020 Jan;22(1):92-102. doi: 10.1002/ejhf.1645. Epub 2019 Dec 20.
PubMed 31863522Butler J, Yang M, Sawhney B, Chakladar S, Yang L, Djatche LM. Treatment patterns and clinical outcomes among patients <65 years with a worsening heart failure event. Eur J Heart Fail. 2021 Aug;23(8):1334-1342. doi: 10.1002/ejhf.2252. Epub 2021 Jun 17.
PubMed 34053163Fiuzat M, Ezekowitz J, Alemayehu W, Westerhout CM, Sbolli M, Cani D, Whellan DJ, Ahmad T, Adams K, Pina IL, Patel CB, Anstrom KJ, Cooper LS, Mark D, Leifer ES, Felker GM, Januzzi JL, O'Connor CM. Assessment of Limitations to Optimization of Guideline-Directed Medical Therapy in Heart Failure From the GUIDE-IT Trial: A Secondary Analysis of a Randomized Clinical Trial. JAMA Cardiol. 2020 Jul 1;5(7):757-764. doi: 10.1001/jamacardio.2020.0640.
PubMed 32319999Kapelios CJ, Murrow JR, Nuhrenberg TG, Montoro Lopez MN. Effect of mineralocorticoid receptor antagonists on cardiac function in patients with heart failure and preserved ejection fraction: a systematic review and meta-analysis of randomized controlled trials. Heart Fail Rev. 2019 May;24(3):367-377. doi: 10.1007/s10741-018-9758-0.
PubMed 30618017Heidenreich PA, Bozkurt B, Aguilar D, Allen LA, Byun JJ, Colvin MM, Deswal A, Drazner MH, Dunlay SM, Evers LR, Fang JC, Fedson SE, Fonarow GC, Hayek SS, Hernandez AF, Khazanie P, Kittleson MM, Lee CS, Link MS, Milano CA, Nnacheta LC, Sandhu AT, Stevenson LW, Vardeny O, Vest AR, Yancy CW; ACC/AHA Joint Committee Members. 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation. 2022 May 3;145(18):e895-e1032. doi: 10.1161/CIR.0000000000001063. Epub 2022 Apr 1.
PubMed 35363499Najafi F, Jamrozik K, Dobson AJ. Understanding the 'epidemic of heart failure': a systematic review of trends in determinants of heart failure. Eur J Heart Fail. 2009 May;11(5):472-9. doi: 10.1093/eurjhf/hfp029. Epub 2009 Feb 27.
PubMed 19251729Piepoli MF, Adamo M, Barison A, Bestetti RB, Biegus J, Bohm M, Butler J, Carapetis J, Ceconi C, Chioncel O, Coats A, Crespo-Leiro MG, de Simone G, Drexel H, Emdin M, Farmakis D, Halle M, Heymans S, Jaarsma T, Jankowska E, Lainscak M, Lam CSP, Lochen ML, Lopatin Y, Maggioni A, Matrone B, Metra M, Noonan K, Pina I, Prescott E, Rosano G, Seferovic PM, Sliwa K, Stewart S, Uijl A, Vaartjes I, Vermeulen R, Verschuren WM, Volterrani M, Von Haehling S, Hoes A. Preventing heart failure: a position paper of the Heart Failure Association in collaboration with the European Association of Preventive Cardiology. Eur J Prev Cardiol. 2022 Feb 19;29(1):275-300. doi: 10.1093/eurjpc/zwab147.
PubMed 35083485McDonagh TA, Metra M, Adamo M, Gardner RS, Baumbach A, Bohm M, Burri H, Butler J, Celutkiene J, Chioncel O, Cleland JGF, Coats AJS, Crespo-Leiro MG, Farmakis D, Gilard M, Heymans S, Hoes AW, Jaarsma T, Jankowska EA, Lainscak M, Lam CSP, Lyon AR, McMurray JJV, Mebazaa A, Mindham R, Muneretto C, Francesco Piepoli M, Price S, Rosano GMC, Ruschitzka F, Kathrine Skibelund A; ESC Scientific Document Group. 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J. 2021 Sep 21;42(36):3599-3726. doi: 10.1093/eurheartj/ehab368. No abstract available.
PubMed 34447992
Study at a glance
From the registry record, last updated by the sponsor on 16 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pharmacological Optimization in Prevention in Heart Failure: A Sex-gap?
- ClinicalTrials.gov ID
- NCT07295522
- Acronym / sponsor ID
- PopS-HF / PopS-HF
- Conditions
- Heart Failure, Acute Heart Failure, Heart Failure With Reduced Ejection Fraction (HFrEF), Heart Failure With Preserved Ejection Fraction (HFPEF), Heart Failure With Mildly Reduced Ejection Fraction
- Keywords
- heart failure, women, GDMT, Pharmacological Optimization, phase IV, High intensity up-titration, Secondary prevention, Sex differences
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 368 participants (estimated)
- Lead sponsor
- IRCCS Policlinico S. DonatoUniversity, hospital or other
- Collaborators
- Agenzia Italiana del Farmaco
- Study start
- 31 Mar 2026 (actual)
- Primary completion
- 8 Jun 2027 (estimated)
- Study completion
- 8 Jun 2028 (estimated)
- First posted
- 19 Dec 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The goal of this clinical trial is to learn whether a rapid and intensive optimization of heart failure medications in women can improve outcomes after hospitalization for heart failure. It will also investigate the safety and the tolerance of these treatments when given at full guideline-recommended doses.
The main questions it aims to answer are:
- Does intensive medication optimization reduce death or hospital readmissions for heart failure within one year?
- Do women benefit as much as men from intensive and full-dose heart failure therapy?
- Is this treatment protocol safe and feasible also in women?
Researchers will compare two groups of women hospitalized for heart failure:
- High-intensity care: starting and increasing all recommended heart-failure medications as quickly as possible and monitoring patients closely during the first weeks after discharge.
- Usual care: medications are started and adjusted gradually, according to the judgment of the treating cardiologist and the patient's usual care team.
The study will follow participants for 12 months to see whether the high-intensity strategy reduces death, hospital readmission for heart failure, or worsening symptoms. It will also evaluate side effects, medication tolerance, and quality of life.
Participants will be randomly assigned to one of the two groups, attend regular follow-up visits for one year, complete a short quality-of-life questionnaire (EQ-5D).
This study will include about 360 women from 13 hospitals in Italy. It is sponsored by IRCCS Policlinico San Donato and funded by the Italian Medicines Agency (AIFA).
Detailed description
PopS-HF is a phase IV, low-interventional, multicenter randomized controlled trial designed to test whether intensive optimization of guideline directed medical therapy (GDMT), following the STRONG-HF (Safety, Tolerability and Efficacy of Rapid Optimization, Helped by NT-proBNP Testing of Heart Failure Therapies) titration strategy, improves outcomes in women hospitalized for heart failure (HF).
The study also includes a retrospective analysis of national healthcare databases and specialized HF registries from 2018-2023 to evaluate how GDMT are prescribed in real-world practice and to identify sex-related differences in treatment patterns and outcomes.
Eligible patients are women aged 18-85 years hospitalized for acute HF with evidence of congestion and hemodynamic stability before discharge. Exclusion criteria include severe comorbidities, pregnancy, and inability to follow up.
The prospective component randomizes 368 patients to an intensive strategy or usual care, with follow-up visits at 2, 4, 6, 12, 24, 36, and 52 weeks.
The primary endpoint is a composite of all-cause mortality, HF readmission, or worsening HF within 1 year.
Secondary endpoints assess optimization of therapy, side effects, biomarkers (NT-proBNP), and quality of life.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- A parallel-group design is used, with participants randomized 1:1 to receive either high-intensity optimization of guideline-directed medical therapy or usual care.
| Arm | Type | Receives |
|---|---|---|
| Usual care | No intervention | –Participants in the usual care arm will receive sequential introduction and adjustment of guideline-directed medical therapy (GDMT) according to the treating cardiologist or general physician's clinical judgment, following routine practice. Follow-up will occur at weeks 6, 12, 24, 36, and 52 after randomization, with clinical visits and intermediate phone contacts as per standard care. |
| High-intensity care | Experimental | Drug: Guideline-Directed Medical Therapy (GDMT)Participants assigned to the high-intensity arm will begin rapid initiation and optimization of guideline-directed medical therapy (GDMT) according to the STRONG-HF protocol. During hospitalization, eligible therapies (beta-blockers (BB), Angiotensin converting enzyme inhibitor(ACEi) /Angiotensin II receptor blocker (ARB)/Angiotensin Receptor-Neprilysin Inhibitors(ARNI), Mineralocorticoid Receptor Antagonists (MRA), and Sodium-Glucose Co-Transporter inhibitor 2 (SGLT2i) for HFrEF/HFmrEF; MRA and SGLT2i for HFpEF will be prescribed at least at half of the recommended target dose. Further titration toward full optimal doses will be performed within the first 6 weeks if clinically appropriate. Participants will undergo clinical assessments at weeks 2, 4, 6, 12, 24, 36, and 52, with safety monitoring including vital signs, physical examination, and laboratory evaluation (NT-proBNP, electrolytes, kidney function). Additional visits may occur after any up-titration if needed for safety. |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Female patients >18 <85 years.
- 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.
- All measures within 24 hours prior to Randomization of systolic blood pressure ≥ 100 mmHg, and of heart rate ≥ 60 bpm.
- All measures within 24 hours prior to Randomization of serum potassium ≤ 5.0 mEq/L (mmol/L).
- Biomarker criteria for persistent congestion:
Key exclusion criteria (22 listed)
- Male patients
- Age < 18 or > 85 years.
- Mechanical ventilation (not including CPAP/BIPAP) in the 24 hours prior to Screening.
- Significant pulmonary disease contributing substantially to the patients' dyspnoea such as 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.
- 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 or during the index event.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Guideline-Directed Medical Therapy (GDMT)Guideline-directed medical therapy (GDMT) including beta-blockers, ACE inhibitors or ARBs or ARNIs, mineralocorticoid receptor antagonists, and SGLT2 inhibitors, all approved and commercially available, used according to current ESC guidelines. Participants in the high-intensity care arm are assigned to a strategy of rapid initiation and optimization of GDMT based on the STRONG-HF protocol. Eligible therapies (beta-blockers, ACEi/ARB/ARNI, mineralocorticoid receptor antagonists, and SGLT2 inhibitors for HFrEF/HFmrEF; MRA and SGLT2 inhibitors for HFpEF) are started during hospitalization at least at half of the recommended target dose, followed by frequent clinical assessments and dose titration, when clinically appropriate, within 6 weeks. Safety monitoring includes clinical examination, vital signs, laboratory tests (NT-proBNP, electrolytes, kidney function), and additional visits after each titration if needed. | Drug | High-intensity care |
Primary outcome
Composite of all-cause mortality, heart failure (HF) readmission, or worsening HF within 1 year.
Time frame: 12 months
Composite endpoint including occurrence of (1) death from any cause, (2) hospital readmission for heart failure, or (3) clinically assessed worsening of heart failure.
10 secondary outcomes
Optimization of Beta-blocker Therapy
Time frame: 12 months
Optimization of ACEi/ARB/ARNI Therapy
Time frame: 12 months
Optimization of Mineralocorticoid Receptor Antagonists (MRAs)
Time frame: 12 months
Optimization of SGLT2 Inhibitors
Time frame: 12 months
Discontinuation of GDMT due to side effects
Time frame: 12 months
NT-proBNP Changes
Time frame: 12 months
Quality of Life (EQ-5D-5L Score)
Time frame: 12 months
One-year All-Cause Mortality
Time frame: 12 months
One-year Heart Failure Readmission
Time frame: 12 months
One-year Worsening Heart Failure
Time frame: 12 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Oct 2026.
- Background: PubMed 27143684Okumura N, Jhund PS, Gong J, Lefkowitz MP, Rizkala AR, Rouleau JL, Shi VC, Swedberg K, Zile MR, Solomon SD, Packer M, McMurray JJ; PARADIGM-HF Investigators and Committees*. Importance of Clinical Worsening of Heart Failure Treated in the Outpatient Setting: Evidence From the Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure Trial (PARADIGM-HF). Circulation. 2016 Jun 7;133(23):2254-62. doi: 10.1161/CIRCULATIONAHA.115.020729. Epub 2016 Apr 20.
- Background: PubMed 19401125Brotons C, Falces C, Alegre J, Ballarin E, Casanovas J, Cata T, Martinez M, Moral I, Ortiz J, Perez E, Rayo E, Recio J, Roig E, Vidal X. Randomized clinical trial of the effectiveness of a home-based intervention in patients with heart failure: the IC-DOM study. Rev Esp Cardiol. 2009 Apr;62(4):400-8. doi: 10.1016/s1885-5857(09)71667-6. English, Spanish.
- Background: PubMed 36356631Mebazaa 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.
- Background: PubMed 30621948Dewan P, Rorth R, Jhund PS, Shen L, Raparelli V, Petrie MC, Abraham WT, Desai AS, Dickstein K, Kober L, Mogensen UM, Packer M, Rouleau JL, Solomon SD, Swedberg K, Zile MR, McMurray JJV. Differential Impact of Heart Failure With Reduced Ejection Fraction on Men and Women. J Am Coll Cardiol. 2019 Jan 8;73(1):29-40. doi: 10.1016/j.jacc.2018.09.081.
- Background: PubMed 31863522Lainscak M, Milinkovic I, Polovina M, Crespo-Leiro MG, Lund LH, Anker SD, Laroche C, Ferrari R, Coats AJS, McDonagh T, Filippatos G, Maggioni AP, Piepoli MF, Rosano GMC, Ruschitzka F, Simic D, Asanin M, Eicher JC, Yilmaz MB, Seferovic PM; European Society of Cardiology Heart Failure Long-Term Registry Investigators Group. Sex- and age-related differences in the management and outcomes of chronic heart failure: an analysis of patients from the ESC HFA EORP Heart Failure Long-Term Registry. Eur J Heart Fail. 2020 Jan;22(1):92-102. doi: 10.1002/ejhf.1645. Epub 2019 Dec 20.
- Background: PubMed 34053163Butler J, Yang M, Sawhney B, Chakladar S, Yang L, Djatche LM. Treatment patterns and clinical outcomes among patients <65 years with a worsening heart failure event. Eur J Heart Fail. 2021 Aug;23(8):1334-1342. doi: 10.1002/ejhf.2252. Epub 2021 Jun 17.
- Background: PubMed 32319999Fiuzat M, Ezekowitz J, Alemayehu W, Westerhout CM, Sbolli M, Cani D, Whellan DJ, Ahmad T, Adams K, Pina IL, Patel CB, Anstrom KJ, Cooper LS, Mark D, Leifer ES, Felker GM, Januzzi JL, O'Connor CM. Assessment of Limitations to Optimization of Guideline-Directed Medical Therapy in Heart Failure From the GUIDE-IT Trial: A Secondary Analysis of a Randomized Clinical Trial. JAMA Cardiol. 2020 Jul 1;5(7):757-764. doi: 10.1001/jamacardio.2020.0640.
- Background: PubMed 30618017Kapelios CJ, Murrow JR, Nuhrenberg TG, Montoro Lopez MN. Effect of mineralocorticoid receptor antagonists on cardiac function in patients with heart failure and preserved ejection fraction: a systematic review and meta-analysis of randomized controlled trials. Heart Fail Rev. 2019 May;24(3):367-377. doi: 10.1007/s10741-018-9758-0.
- Background: PubMed 35363499Heidenreich PA, Bozkurt B, Aguilar D, Allen LA, Byun JJ, Colvin MM, Deswal A, Drazner MH, Dunlay SM, Evers LR, Fang JC, Fedson SE, Fonarow GC, Hayek SS, Hernandez AF, Khazanie P, Kittleson MM, Lee CS, Link MS, Milano CA, Nnacheta LC, Sandhu AT, Stevenson LW, Vardeny O, Vest AR, Yancy CW; ACC/AHA Joint Committee Members. 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation. 2022 May 3;145(18):e895-e1032. doi: 10.1161/CIR.0000000000001063. Epub 2022 Apr 1.
- Background: PubMed 19251729Najafi F, Jamrozik K, Dobson AJ. Understanding the 'epidemic of heart failure': a systematic review of trends in determinants of heart failure. Eur J Heart Fail. 2009 May;11(5):472-9. doi: 10.1093/eurjhf/hfp029. Epub 2009 Feb 27.
- Background: PubMed 35083485Piepoli MF, Adamo M, Barison A, Bestetti RB, Biegus J, Bohm M, Butler J, Carapetis J, Ceconi C, Chioncel O, Coats A, Crespo-Leiro MG, de Simone G, Drexel H, Emdin M, Farmakis D, Halle M, Heymans S, Jaarsma T, Jankowska E, Lainscak M, Lam CSP, Lochen ML, Lopatin Y, Maggioni A, Matrone B, Metra M, Noonan K, Pina I, Prescott E, Rosano G, Seferovic PM, Sliwa K, Stewart S, Uijl A, Vaartjes I, Vermeulen R, Verschuren WM, Volterrani M, Von Haehling S, Hoes A. Preventing heart failure: a position paper of the Heart Failure Association in collaboration with the European Association of Preventive Cardiology. Eur J Prev Cardiol. 2022 Feb 19;29(1):275-300. doi: 10.1093/eurjpc/zwab147.
- Background: PubMed 34447992McDonagh TA, Metra M, Adamo M, Gardner RS, Baumbach A, Bohm M, Burri H, Butler J, Celutkiene J, Chioncel O, Cleland JGF, Coats AJS, Crespo-Leiro MG, Farmakis D, Gilard M, Heymans S, Hoes AW, Jaarsma T, Jankowska EA, Lainscak M, Lam CSP, Lyon AR, McMurray JJV, Mebazaa A, Mindham R, Muneretto C, Francesco Piepoli M, Price S, Rosano GMC, Ruschitzka F, Kathrine Skibelund A; ESC Scientific Document Group. 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J. 2021 Sep 21;42(36):3599-3726. doi: 10.1093/eurheartj/ehab368. No abstract available.
- Individual participant dataSharing planned: No. De-identified individual participant data (IPD) will not be made publicly available. Data sharing is restricted due to ethical and regulatory requirements under GDPR and Italian data protection regulations. Aggregate study results will be published.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
12 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Guideline-Directed Medical Therapy (GDMT) in people with Heart Failure and Acute Heart Failure, run by IRCCS Policlinico S. Donato at 12 sites in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 16 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 12 sites in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Massimo Piepoli, MD (0252774966, MASSIMO.PIEPOLI@GRUPPOSANDONATO.IT), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Composite of all-cause mortality, heart failure (HF) readmission, or worsening HF within 1 year. (time frame: 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07295522, which also lists 12 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Oct 2026.