An interventional study of M-TEER and Standardized GDMT Up-Titration in Mitral Regurgitation Functional and Heart Failure With Reduced Ejection Fraction (HFrEF), sponsored by University Medical Center Mainz. Recruiting at 1 site in Germany. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-11-02.
Sponsored by University Medical Center Mainz · Not applicable, Interventional, and Treatment
The purpose of the ACHILLES-HF trial (ACHIeving optimaL medicaL therapy through pErcutaneous treatment of Secondary mitral regurgitation to improve outcome in Patients with Heart Failure with reduced ejection fraction) is to test whether early transcatheter edge-to-edge repair (TEER) in patients with heart failure and reduced ejection fraction (HFrEF) and relevant secondary mitral regurgitation, that are at risk of not receiving full guideline recommended therapy (GDMT), results in faster and more complete GDMT up-titration and whether this translates into improved quality of life and clinical outcomes.
468 studies on the registry are indexed under Mitral Valve Insufficiency; 164 are open to participants now.
This study's planned enrollment of 520 is above the median of 68 across 279 interventional studies indexed under Mitral Valve Insufficiency.
Browse Mitral Valve Insufficiency studies →University Medical Center Mainz is the lead sponsor of 8 studies on the registry; 4 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Risk factor for not intensification of guideline directed medical therapy (at least one of the following):
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
The share of blood the heart’s main pumping chamber (the left ventricle) pushes out with each beat, measured by an echocardiogram (heart ultrasound) or a MUGA scan. About 50–70% is normal.
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
The New York Heart Association’s four classes of how much heart failure limits physical activity.
Studies set their own limit — many outside heart failure leave out class III–IV, while heart failure studies may ask for a particular class. Check the class this study names.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
The study doctor’s estimate of how long someone is likely to live. Criteria use it so that people can stay in the study long enough for it to answer its question.
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
LVEF (left ventricular ejection fraction)
The share of blood the heart’s main pumping chamber (the left ventricle) pushes out with each beat, measured by an echocardiogram (heart ultrasound) or a MUGA scan. About 50–70% is normal.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Clinically significant
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
GFR and eGFR (kidney filtering)
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
NYHA class (heart failure)
The New York Heart Association’s four classes of how much heart failure limits physical activity.
Studies set their own limit — many outside heart failure leave out class III–IV, while heart failure studies may ask for a particular class. Check the class this study names.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Life expectancy
The study doctor’s estimate of how long someone is likely to live. Criteria use it so that people can stay in the study long enough for it to answer its question.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hypersensitivity
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraindication
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Subjects randomized to this arm undergo transcatheter edge-to-edge repair (M-TEER) of the mitral valve within 7 days of randomization, in addition to a standardized, protocol-driven guideline-directed medical therapy (GDMT) up-titration regimen. Starting on the first post-procedural day, subjects are up-titrated toward optimal target doses of a beta-blocker, ACE inhibitor/ARB/ARNI, a mineralocorticoid receptor antagonist, and an SGLT2 inhibitor, guided by protocol-defined thresholds for blood pressure, heart rate, potassium, and renal function, with formal safety/tolerability reassessment at 2, 4, 6, 8, 10, and 12 weeks.
Device: M-TEER · Other: Standardized GDMT Up-Titration
Subjects randomized to this arm receive the identical standardized, protocol-driven GDMT up-titration regimen as the Intervention group, without early M-TEER. Up-titration toward optimal target doses of a beta-blocker, ACE inhibitor/ARB/ARNI, a mineralocorticoid receptor antagonist, and an SGLT2 inhibitor begins at randomization and follows the same protocol-defined safety thresholds and visit schedule (2, 4, 6, 8, 10, and 12 weeks) as the Intervention group. Subjects may cross over to M-TEER or mitral valve surgery after completion of the 12-week follow-up visit, or earlier in the case of an intervening heart failure hospitalization.
Other: Standardized GDMT Up-Titration
Transcatheter edge-to-edge repair (M-TEER) of the mitral valve, performed once, within 7 days of randomization, in subjects randomized to the Intervention arm.
A protocol-driven regimen applied to all randomized subjects, beginning at randomization (Control arm) or on the first post-procedural day (Intervention arm). Subjects are started on a beta-blocker, ACE inhibitor/ARB/ARNI, a mineralocorticoid receptor antagonist, and an SGLT2 inhibitor, targeting at least half of each drug's optimal dose immediately (full dose for the SGLT2 inhibitor), with same-day achievement recommended if hemodynamically stable. Formal reassessment occurs at 2, 4, 6, 8, 10, and 12 weeks, with up-titration to full optimal doses of beta-blocker, ACEi/ARB/ARNI, and MRA targeted by week 6, contingent on tolerability. Medications are not up-titrated if systolic blood pressure is \<95 mmHg, potassium is \>5.0 mmol/L, eGFR is \<30 mL/min/1.73m², or heart rate is \<55 bpm (beta-blocker only); diuretic dose reduction is encouraged if eGFR is \<30 mL/min/1.73m². Safety and tolerability are formally reassessed at weeks 2, 4, 6, 10, and 12.
Difference in Guideline-Directed Medical Therapy (GDMT) Score at 12 Weeks
Between-group difference in GDMT intensity score, a 0-12 point composite scoring dosing of ACE inhibitor/ARB/ARNI, beta-blocker, mineralocorticoid receptor antagonist, and SGLT2 inhibitor relative to trial-defined target doses (0-\[2\]3 points per drug class). Analyzed via a mixed model for repeated measures (fixed effects for site, age group, sex, NYHA class, treatment, visit, and treatment-by-visit interaction; baseline score as covariate; first-order autoregressive covariance structure). Higher scores indicate more complete guideline-directed therapy.
Time frame: Baseline and 12 weeks post-randomization (post-procedure for Intervention group)
Difference in Quality of Life (KCCQ Score) at 12 Weeks
Between-group difference in quality of life among surviving patients, assessed by the Kansas City Cardiomyopathy Questionnaire (KCCQ) overall score (range 0-100, higher scores indicate better health status), from baseline to 12 weeks. Analyzed via two-sample t-test.
Time frame: Baseline and 12 weeks post-randomization (post-procedure for Intervention group), among surviving patients
Composite of Cardiovascular Death or First Heart Failure Hospitalization at 24 Months
Time to the first occurrence of cardiovascular death or heart failure hospitalization within 24 months of randomization, centrally adjudicated by an independent Clinical Events Committee blinded to treatment allocation.
Time frame: From randomization to 24 months
Win Ratio for Cardiovascular Mortality, First Heart Failure Hospitalization, KCCQ Improvement, or GDMT Score Improvement at 24 Months
Hierarchical composite of cardiovascular death, first heart failure hospitalization, a Kansas City Cardiomyopathy Questionnaire (KCCQ) improvement of more than 5 points, and a GDMT score improvement of more than 2 points, ranked in that order and compared between groups using the Finkelstein-Schoenfeld win ratio method. Win ratio and 95% confidence interval reported.
Time frame: From randomization to 24 months (GDMT and KCCQ improvement assessed at 12 weeks)
Total Heart Failure Hospitalizations Through 24 Months
Total number of first and recurrent heart failure hospitalizations through 24 months, with cardiovascular death analyzed as a terminal heart failure hospitalization event. Analyzed using the Lin-Wei-Yang-Ying (LWYY) model for recurrent events; treatment effect reported as a rate ratio with 95% confidence interval.
Time frame: From randomization to 24 months
Mitral Regurgitation Severity at 24 Months
Proportion of subjects with residual mitral regurgitation severity of grade 2+ or less at 24 months. Analyzed by logistic regression adjusted for baseline MR grade and etiology; odds ratio and 95% confidence interval reported.
Time frame: 24 months
NYHA Functional Class Improvement at 12 Months
Proportion of subjects with an improvement of at least one NYHA functional class from baseline to 12 months. Analyzed using Fisher's exact test; between-group difference in proportions reported with 95% confidence interval.
Time frame: Baseline and 12 months
Change in Left Ventricular End-Diastolic Volume (LVEDV) from Baseline to 12 Months
Change in left ventricular end-diastolic volume, assessed by echocardiography, from baseline to 12 months, reflecting reverse left ventricular remodeling. Analyzed using a two-sample t-test; mean between-group difference reported with 95% confidence interval.
Time frame: Baseline and 12 months
All-Cause Mortality Within 24 Months
All-cause mortality within 24 months of randomization. Analyzed using a Cox proportional hazards model stratified by country and heart failure etiology; hazard ratio and 95% confidence interval reported with Kaplan-Meier estimates.
Time frame: From randomization to 24 months
Need for Mitral Valve Re-Intervention
Occurrence of mitral valve re-intervention, surgical or transcatheter, during follow-up. Analyzed using Fisher's exact test; proportion and 95% confidence interval reported for each group, along with the between-group difference.
Time frame: From randomization to 24 months
Composite 30-Day Safety Endpoint (Device-Related MACE)
Time frame: 30 days post-procedure (Intervention group)
All-Cause Mortality at 30 Days
Time frame: 30 days
All-Cause Mortality Through End of Follow-Up
Time frame: From randomization through 24 months
Freedom from GDMT Up-Titration Complications at 24 Months
Time frame: From randomization to 24 months
Major Adverse Events (MAE) at 24 Months
Composite of stroke, myocardial infarction, new need for renal-replacement therapy, non-elective cardiovascular surgery for device-related complications, new-onset atrial fibrillation, endocarditis, gastrointestinal complication requiring surgery, TIMI-defined major bleeding, and cardiac tamponade. Reported descriptively by treatment group as event rates.
Time frame: From randomization to 24 months
Plan to share: Yes — De-identified individual participant data underlying the primary and secondary endpoint analyses will be made available, together with the study protocol, statistical analysis plan, and informed consent form.
Supporting information: Study protocol, Statistical analysis plan, Informed consent form
Time frame: Individual participant data and supporting documents (protocol, statistical analysis plan, informed consent form) will be available beginning 9 months after publication of the primary trial results and ending 36 months after publication.
Access criteria: Requests will be considered from researchers who provide a methodologically sound research proposal, beginning after publication of the primary trial results and continuing for a defined period thereafter. Access requires review and approval by the ACHILLES-HF Publication Committee and execution of a data use agreement. Data will be shared in a de-identified format consistent with EU data protection requirements (GDPR) and the informed consent provided by trial participants.
Started Oct 2026 (actual). Primary completion is estimated for Sep 2030, 47 months after the start.
Of 143 interventional studies with no phase under Mitral Valve Insufficiency, half reached primary completion within 56 months of starting (the median), counting those still running; a quarter within 25 and three quarters within 108. This study's planned 47 months is below that.
Start moved once since we started tracking on Sep 25, 2026: Aug 2026 → Oct 2026, on Nov 2, 2026.
Earlier changes are on the record history on ClinicalTrials.gov ↗
How these figures are worked out, and which studies are left out of them.
From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗
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University Medical Center Mainz