Overview
Sponsor-declared trial summary
Phase
Therapeutic confirmatory (Phase III)
Status
Ongoing, recruiting
Participants planned
44
Countries
1
Sites
1
congestive heart failure
To compare two different treatment strategies (control arm treated with loop diuretic and potassium sparing and experimental arm that will combine such therapy with acetazolamide and free-dose metolazone) in patients with chronic heart failure.
Key facts
- Sponsor
- Centro Cardiologico Monzino S.p.A.
- Participant type
- Patients
- Age range
- 18-64 years, 65+ years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Cardiovascular Diseases [C14]
- Trial duration
- 21 Sep 2023 → ongoing
- Decision date (initial)
- 2025-03-11
- Transition trial
- Yes
- Low-intervention
- No
- Rare-disease indication
- No
- Vulnerable population
- No
External identifiers
- EU CT number
- 2024-519565-21-01
- EudraCT number
- 2022-003314-37
- WHO UTN
- U1111-1316-2467
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Therapy
To compare two different treatment strategies (control arm treated with loop diuretic and potassium sparing and experimental arm that will combine such therapy with acetazolamide and free-dose metolazone) in patients with chronic heart failure.
Secondary objectives 4
- Assess the degree of congestion and volemia through the course of body weight and measurement of vector impedance (BIVA) between patients with chronic heart failure treated with standard diuretic therapy and combined diuretic therapy
- To evaluate differences in the effects on functional capacity through CPET with VO2 max measurement and on alveolar-capillary diffusion between patients with chronic heart failure treated with standard diuretic therapy and combined diuretic therapy
- Assess differences in the trend of subjective perception of health through Kansas City Cardiomiopathy Questioning between patients with chronic heart failure treated with standard diuretic therapy and combined diuretic therapy
- Assess differences in neurohormonal response by measuring NT-proBNP between patients with chronic heart failure treated with standard diuretic therapy and combined diuretic therapy
Conditions and MedDRA coding
congestive heart failure
| Version | Level | Code | Term | System organ class |
|---|---|---|---|---|
| 20.0 | SOC | 10007541 | Cardiac disorders | 11 |
Regulatory references
- Plan to share IPD
- No
| EU CT number | Title | Sponsor |
|---|---|---|
| 2024-519565-21-00 | Effects of combined diuretic therapy on exercise capacity, alveolar-capillary diffusion and maintenance of euvolemia in chronic congestive heart failure, diuretic therapy compared with loop diuretics and potassium-sparing diuretics | Centro Cardiologico Monzino S.p.A. |
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 5
- written informed consent signed
- Age: 18-80
- Patients with chronic heart failure (at reduced or preserved ejection fraction)
- Patients discharged after hospitalization for acute heart failure (at least second episode of decompensation in the past 12 months)
- Patients being treated with loop diuretics at the same or higher dosage of furosemide 40 mg (or equivalent) at the time of admission
Exclusion criteria 6
- age <18 years or >85 years
- patients with severe aortic stenosis
- patients with severe renal failure (eGFR<20 ml/min/1.73m2 according to CockroftGault)
- patients with severe hyponatremia
- Medical therapy for heart failure optimized during hospitalization
- Documented current pregnancy and lactating status in women of childbearing potential
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- Evaluate differences in the trend of short- to medium-term re-hospitalizations between chronic heart failure patients treated with standard diuretic therapy (control arm) and combination diuretic therapy (experimental arm)
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 3
PRD391182 · Product
- Active substance
- Metolazone
- Pharmaceutical form
- TABLET
- Route of administration
- ORAL USE
- Max daily dose
- 5 mg milligram(s)
- Max total dose
- 5 mg milligram(s)
- Max treatment duration
- 3 Month(s)
- Authorisation status
- Authorised
- ATC code
- C03BA08 — METOLAZONE
- Marketing authorisation
- 024488090
- MA holder
- TEOFARMA S.R.L.
- MA country
- Italy
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
PRD391081 · Product
- Active substance
- Metolazone
- Pharmaceutical form
- TABLET
- Route of administration
- ORAL USE
- Max daily dose
- 5 mg milligram(s)
- Max total dose
- 5 mg milligram(s)
- Max treatment duration
- 3 Month(s)
- Authorisation status
- Authorised
- ATC code
- C03BA08 — METOLAZONE
- Marketing authorisation
- 024488 064
- MA holder
- TEOFARMA S.R.L.
- MA country
- Italy
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
PRD350190 · Product
- Active substance
- Acetazolamide
- Pharmaceutical form
- TABLET
- Route of administration
- ORAL USE
- Max daily dose
- 750 mg milligram(s)
- Max total dose
- 750 mg milligram(s)
- Max treatment duration
- 3 Month(s)
- Authorisation status
- Authorised
- ATC code
- S01EC01 — ACETAZOLAMIDE
- Marketing authorisation
- 009277017
- MA holder
- TEOFARMA S.R.L.
- MA country
- Italy
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Centro Cardiologico Monzino S.p.A.
- Sponsor organisation
- Centro Cardiologico Monzino S.p.A.
- Address
- Via Carlo Parea 4
- City
- Milan
- Postcode
- 20138
- Country
- Italy
Scientific contact point
- Organisation
- Centro Cardiologico Monzino S.p.A.
- Contact name
- Prof. Piergiuseppe Agostoni
Public contact point
- Organisation
- Centro Cardiologico Monzino S.p.A.
- Contact name
- Prof. Piergiuseppe Agostoni
Locations
1 EU/EEA country · 1 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Italy | Ongoing, recruiting | 44 | 1 |
| Rest of world | — | 0 | — |
Investigational sites
Country notifications
Trial-start, recruitment-start, end and early-termination notifications submitted per Member State
| Country | Trial start | Trial end | Recruitment start | Recruitment end | Early termination |
|---|---|---|---|---|---|
| Italy | 2023-09-21 | 2023-12-21 |
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 12 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Protocol (for publication) | D1_Protocol EU CT number 2024-519565-21-01_Annex 1 | 1.2 |
| Protocol (for publication) | D1_Protocol 2022-003314-37 redacted | 4.0 |
| Protocol (for publication) | D4_Patient facing documents_KCCQ-12 ITA EU CT number 2024-519565-21-01 | 1 |
| Protocol (for publication) | Elenco variabili_DIURETICI | 1 |
| Recruitment arrangements (for publication) | Blank letter | 1 |
| Recruitment arrangements (for publication) | K1_Recruitment arrangements_v1 21Jul25 | 1 |
| Subject information and informed consent form (for publication) | L1 ICF 2022-003314-37 redacted | 3.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Privacy notice_EU CT number 2024-519565-21-01 _v 3 21Jul25 redacted | 3.0 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_RCP_DIAMOX 2022-003314-37 | 2 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_RCP_ZAROXOLYN 2022-003314-37 | 2 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_RCP_ZAROXOLYN 2022-003314-37 | 2 |
| Synopsis of the protocol (for publication) | D1_Protocol synopsis ITA EU CT number 2024-519565-21-01_v 1 21Jul25 | 1.0 |
Application history
2 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2025-01-23 | Italy | Acceptable with conditions 2025-01-30
|
2025-03-11 |
| 2 | SUBSTANTIAL MODIFICATION | SM-1 | 2025-09-10 | Italy | Acceptable 2025-12-15
|
2025-12-18 |