Heart Failure, SystolicPhase 3COMBINED-HFNCT06434025
IV Iron and SGLT2 Inhibitor on Ventricular Function and Myocardial Iron Content in Heart Failure With Iron Deficiency
A Phase 3 study testing Iron Carboxymaltose and Dapagliflozin 10mg Tab in people with Heart Failure, Systolic and Iron Deficiencies, run by Hospital de Clinicas de Porto Alegre at 1 site in Brazil.
Trial summary
Background. Treatment with intravenous iron has been shown to improve symptoms, functional capacity, and quality of life in patients with heart failure with reduced ejection fraction (HFrEF) and iron deficiency. However, the mechanisms underlying these beneficial effects remain unknown. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Heart Failure, Systolic, Iron Deficiencies
- What is being tested?
- Iron Carboxymaltose and Dapagliflozin 10mg Tab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 99 participants
- Where
- 1 siteBrazil
- Study dates
- 24 May 2024to 24 Nov 2026
- Phase
- Phase 3
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age 18 years or over;
- Ejection fraction (EF) ≤40%, estimated by color Doppler echocardiography or CMR or radionuclide ventriculography;
- Serum ferritin <100 µg/L or serum ferritin between 100 and 299 µg/L and transferrin saturation <20%;
- Serum hemoglobin between 9.5 and 13.5 mg/dL;
- Patients must be SGLT2 naive;
- Informed consent form (ICF) signed.
Who cannot join
- Kidney disease requiring dialysis or chronic kidney disease not requiring dialysis with an estimated glomerular filtration rate <30 mL/min/1.73 m2 calculated by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation;
- Severe primary valve disease;
- Acute coronary syndrome requiring cardiac surgery or coronary artery bypass surgery in the past 3 months;
- Patients already being treated for some type of non-iron deficiency anemia;
- Blood transfusion within 30 days prior to CMR examination;
- Patients with a pacemaker, cardiac resynchronization therapy, or implantable defibrillator;
- Diagnosis of hemochromatosis.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Brazil1 site
Hospital de Clínicas de Porto Alegre
Porto Alegre, Rio Grande do Sul, 90450120
Ana Paula Silveira, BMD, 55 51 33596223, apbsilveira@hcpa.edu.br
Marcia Raymundo, 55 51 33596224, mraymundo@hcpa.edu.br
About this study
Official title: Effect of Combination of Intravenous Iron and SGLT2 Inhibitor on Ventricular Function and Myocardial Iron Content in Patients With Heart Failure and Iron Deficiency.
Background. Treatment with intravenous iron has been shown to improve symptoms, functional capacity, and quality of life in patients with heart failure with reduced ejection fraction (HFrEF) and iron deficiency. However, the mechanisms underlying these beneficial effects remain unknown. SGLT2i seem to alter hematocrit and other hematological markers or iron content.
This study aims to measure cardiac magnetic resonance changes in myocardial iron content and in left ventricular function after administration of intravenous iron with and without the concomitant use of SGLT2 inhibitor in patients with HFrEF and iron deficiency.
Read the detailed description
Background. Treatment with intravenous iron has been shown to improve symptoms, functional capacity, and quality of life in patients with heart failure with reduced ejection fraction (HFrEF) and iron deficiency. However, the mechanisms underlying these beneficial effects remain unknown. SGLT2i seem to alter hematocrit and other hematological markers or iron content. This study aims to measure cardiac magnetic resonance changes in myocardial iron content after administration of intravenous iron and to assess changes in left ventricular function in patients with HFrEF and iron deficiency.
Methods. Ninety-nine outpatient with symptomatic HFrEF, left ventricular ejection fraction (LVEF) <40%, SGLT2i naive, and iron deficiency will be assigned, to receive intravenous iron + SGLT2i; or intravenous iron + placebo of SGLT2i; or placebo of both therapies for 30 days. Myocardial iron will be evaluated by T2-star (T2*) cardiac magnetic resonance (CMR) sequencing before intravenous iron infusion. After 30 days, all patients will be reassessed by T2* CMR sequencing. The primary endpoint will be changes in LVEF and myocardial iron content at 30 days. Secondary endpoints will include correlations of these changes with myocardial iron content, functional capacity, quality of life, and cardiac biomarkers.
Conclusions. This study will determine the effect of ferric carboxymaltose and its combination with SGLT2i on LVEF and its relationship with measures of myocardial iron content, functional capacity, and biomarkers in HFrEF and iron deficiency.
- Conditions
- Heart Failure, Systolic, Iron Deficiencies
- Being tested
- Iron Carboxymaltose, Dapagliflozin 10mg Tab, Placebo of Iron Carboxymaltose, Placebo of Dapagliflozin
- Keywords
- heart failure, iron deficiency, SGLT2 inhibitor, intravenous iron, clinical trial
- Medical subject headings
- Heart Failure, Systolic, Iron Deficiencies, Heart Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Iron CarboxymaltoseDrug
Also called Ferinject
Iron Carboxymaltose 500 mg. 2 vials administered IV.
Dapagliflozin 10mg TabDrug
Also called Forxiga
Dapagliflozin 10mg Tab, PO, onde a day.
Placebo of Iron CarboxymaltoseDrug
Also called Saline
Solution Sodium Chloride 0,9% 100 ml, IV, once.
Placebo of DapagliflozinDrug
Equal shape and appearance tab as the tab containing Dapagliflozin 10 mg
| Study group | Role | What they receive |
|---|---|---|
| ferric carboxymaltose + SGLT2 inhibitor | Experimental | Patients will receive 2 vials of ferric carboxymaltose 500 mg (Ferinject® 500 mg, Vifor-Pharma) IV, once; and Dapagliflozin 10 mg PO, once a day, for 30 days. Receives: Drug: Iron Carboxymaltose; Drug: Dapagliflozin 10mg Tab |
| ferric carboxymaltose + placebo of SGLT2 inhibitor | Active comparator | Patients will receive 2 vials of ferric carboxymaltose 500 mg (Ferinject® 500 mg, Vifor-Pharma) IV, once; and placebo PO, once a day, for 30 days. Receives: Drug: Iron Carboxymaltose; Drug: Placebo of Dapagliflozin |
| Placebo of ferric carboxymaltose and placebo of SGLT2 inhibitor | Placebo comparator | Patients will receive 2 vials of placebo IV, once; and placebo PO, once a day, for 30 days. Receives: Drug: Placebo of Iron Carboxymaltose; Drug: Placebo of Dapagliflozin |
What is being measured
The primary outcome is the main question the study is designed to answer.
left ventricular function assessed (LVEF) by CMR.
LVEF assessed by Cardiac Magnetic Resonance
Measured: 30 days
Secondary outcomes (2)
Myocardial iron content assessed by T2* CMR
Myocardial iron content assessed by T2* CMR
Measured: 30 days
myocardial strain assessed by T2* CMR
myocardial strain assessed by T2* CMR
Measured: 30 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 May 2024
- Study start24 May 2024 (estimated)
- Primary completion24 May 2026 (estimated)
- Study completion24 Nov 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Heart Failure, SystolicStudies of the same condition, open and under way.
- More trials run by Hospital de Clinicas de Porto AlegreThe 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- HFrEF, LVEF \<40%, SGLT2i naive, and iron deficiency. Assigned to receive: 1. intravenous iron + SGLT2i; 2. intravenous iron + placebo of SGLT2i; 3. placebo of both therapies.
- Masking
- Triple blind
- Who is masked
- Care provider, Investigator, Outcomes assessor
- Enrolment
- 99 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Hospital de Clinicas de Porto Alegre
- Sponsor type
- University, hospital or other
- Collaborators
- Vifor Pharma
- Responsible party
- Principal investigator, Luis Beck Da Silva Neto, Hospital de Clinicas de Porto Alegre
- Investigators
- LUIS BECK DA SILVA, MD ScD, Principal investigator, Hospital de Clinicas de Porto Alegre
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06434025
- Sponsor's protocol ID
- 78861724.0.0000.5327
- Other IDs
- 2023-0428
- Acronym
- COMBINED-HF
- Status last verified
- May 2024
- First submitted
- 23 May 2024
- Last updated
- 3 Jun 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 Jun 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Combination of Intravenous Iron and SGLT2 Inhibitor on Ventricular Function and Myocardial Iron Content in Patients With Heart Failure and Iron Deficiency.
- ClinicalTrials.gov ID
- NCT06434025
- Acronym / sponsor ID
- COMBINED-HF / 78861724.0.0000.5327
- Conditions
- Heart Failure, Systolic, Iron Deficiencies
- Keywords
- heart failure, iron deficiency, SGLT2 inhibitor, intravenous iron, clinical trial
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 99 participants (estimated)
- Lead sponsor
- Hospital de Clinicas de Porto AlegreUniversity, hospital or other
- Collaborators
- Vifor Pharma
- Study start
- 24 May 2024 (estimated)
- Primary completion
- 24 May 2026 (estimated)
- Study completion
- 24 Nov 2026 (estimated)
- First posted
- 30 May 2024 (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.
Background. Treatment with intravenous iron has been shown to improve symptoms, functional capacity, and quality of life in patients with heart failure with reduced ejection fraction (HFrEF) and iron deficiency. However, the mechanisms underlying these beneficial effects remain unknown. SGLT2i seem to alter hematocrit and other hematological markers or iron content.
This study aims to measure cardiac magnetic resonance changes in myocardial iron content and in left ventricular function after administration of intravenous iron with and without the concomitant use of SGLT2 inhibitor in patients with HFrEF and iron deficiency.
Detailed description
Background. Treatment with intravenous iron has been shown to improve symptoms, functional capacity, and quality of life in patients with heart failure with reduced ejection fraction (HFrEF) and iron deficiency. However, the mechanisms underlying these beneficial effects remain unknown. SGLT2i seem to alter hematocrit and other hematological markers or iron content. This study aims to measure cardiac magnetic resonance changes in myocardial iron content after administration of intravenous iron and to assess changes in left ventricular function in patients with HFrEF and iron deficiency.
Methods. Ninety-nine outpatient with symptomatic HFrEF, left ventricular ejection fraction (LVEF) <40%, SGLT2i naive, and iron deficiency will be assigned, to receive intravenous iron + SGLT2i; or intravenous iron + placebo of SGLT2i; or placebo of both therapies for 30 days. Myocardial iron will be evaluated by T2-star (T2*) cardiac magnetic resonance (CMR) sequencing before intravenous iron infusion. After 30 days, all patients will be reassessed by T2* CMR sequencing. The primary endpoint will be changes in LVEF and myocardial iron content at 30 days. Secondary endpoints will include correlations of these changes with myocardial iron content, functional capacity, quality of life, and cardiac biomarkers.
Conclusions. This study will determine the effect of ferric carboxymaltose and its combination with SGLT2i on LVEF and its relationship with measures of myocardial iron content, functional capacity, and biomarkers in HFrEF and iron deficiency.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (care provider, investigator, outcomes assessor)
- Number of arms
- 3
- Model description
- HFrEF, LVEF <40%, SGLT2i naive, and iron deficiency. Assigned to receive: 1. intravenous iron + SGLT2i; 2. intravenous iron + placebo of SGLT2i; 3. placebo of both therapies.
| Arm | Type | Receives |
|---|---|---|
| ferric carboxymaltose + SGLT2 inhibitor | Experimental | Drug: Iron Carboxymaltose, Drug: Dapagliflozin 10mg TabPatients will receive 2 vials of ferric carboxymaltose 500 mg (Ferinject® 500 mg, Vifor-Pharma) IV, once; and Dapagliflozin 10 mg PO, once a day, for 30 days. |
| ferric carboxymaltose + placebo of SGLT2 inhibitor | Active comparator | Drug: Iron Carboxymaltose, Drug: Placebo of DapagliflozinPatients will receive 2 vials of ferric carboxymaltose 500 mg (Ferinject® 500 mg, Vifor-Pharma) IV, once; and placebo PO, once a day, for 30 days. |
| Placebo of ferric carboxymaltose and placebo of SGLT2 inhibitor | Placebo comparator | Drug: Placebo of Iron Carboxymaltose, Drug: Placebo of DapagliflozinPatients will receive 2 vials of placebo IV, once; and placebo PO, once a day, for 30 days. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Age 18 years or over;
- Ejection fraction (EF) ≤40%, estimated by color Doppler echocardiography or CMR or radionuclide ventriculography;
- Serum ferritin <100 µg/L or serum ferritin between 100 and 299 µg/L and transferrin saturation <20%;
- Serum hemoglobin between 9.5 and 13.5 mg/dL;
- Patients must be SGLT2 naive;
Key exclusion criteria (7 listed)
- Kidney disease requiring dialysis or chronic kidney disease not requiring dialysis with an estimated glomerular filtration rate <30 mL/min/1.73 m2 calculated by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation;
- Severe primary valve disease;
- Acute coronary syndrome requiring cardiac surgery or coronary artery bypass surgery in the past 3 months;
- Patients already being treated for some type of non-iron deficiency anemia;
- Blood transfusion within 30 days prior to CMR examination;
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 |
|---|---|---|
| Iron CarboxymaltoseAlso: FerinjectIron Carboxymaltose 500 mg. 2 vials administered IV. | Drug | ferric carboxymaltose + SGLT2 inhibitor, ferric carboxymaltose + placebo of SGLT2 inhibitor |
| Dapagliflozin 10mg TabAlso: ForxigaDapagliflozin 10mg Tab, PO, onde a day. | Drug | ferric carboxymaltose + SGLT2 inhibitor |
| Placebo of Iron CarboxymaltoseAlso: SalineSolution Sodium Chloride 0,9% 100 ml, IV, once. | Drug | Placebo of ferric carboxymaltose and placebo of SGLT2 inhibitor |
| Placebo of DapagliflozinEqual shape and appearance tab as the tab containing Dapagliflozin 10 mg | Drug | Placebo of ferric carboxymaltose and placebo of SGLT2 inhibitor, ferric carboxymaltose + placebo of SGLT2 inhibitor |
Primary outcome
left ventricular function assessed (LVEF) by CMR.
Time frame: 30 days
LVEF assessed by Cardiac Magnetic Resonance
2 secondary outcomes
Myocardial iron content assessed by T2* CMR
Time frame: 30 days
myocardial strain assessed by T2* CMR
Time frame: 30 days
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 3 Jun 2024.
- Individual participant dataSharing planned: No
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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.
LUIS BECK DA SILVA, MD ScD principal investigator
Hospital de Clinicas de Porto Alegre
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Iron Carboxymaltose and Dapagliflozin 10mg Tab in people with Heart Failure, Systolic and Iron Deficiencies, run by Hospital de Clinicas de Porto Alegre at 1 site in Brazil.
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 6 inclusion and 7 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: opening soon, as of the sponsor's last update on 3 Jun 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Brazil. 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. Some participants in this study may receive a placebo. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 LUIS BECK DA SILVA, MD ScD (55 51 997330870, lbneto@hcpa.edu.br), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
left ventricular function assessed (LVEF) by CMR. (time frame: 30 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 3 Jun 2024.