Heart FailurePhase 4LOCO-CHFNCT03576677
Effect of Levosimendan or Placebo on Exercise in Advanced Chronic Heart Failure
A Phase 4 study testing Levosimendan in people with Heart Failure, run by Finn Gustafsson at 3 sites in Denmark.
Trial summary
Purpose: This study evaluates the subacute effect of levosimendan infusion on exercise capacity and exercise hemodynamics compared with placebo in patients with advanced chronic heart failure. Read more about this study
- Who is it for?
- Ages 18 to 100 years
- Conditions the study is for
- Heart Failure
- What is being tested?
- Levosimendan
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 42 participants
- Where
- 3 sitesDenmark
- Study dates
- 1 Aug 2019to 30 Jul 2020
- Phase
- Phase 4
- Are there results?
- None posted in the registry
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 100 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age ≥18 years
- NYHA III-IV on optimal medical treatment
- LVEF ≤35%
- NT-proBNP >600 µg/L
- pVO2 <20 mL/kg/min
- No hospitalization for HF or change in loop diuretic <2 weeks
Who cannot join
- Recent or acute coronary and respiratory syndromes
- Recent sustained ventricular tachycardia or ventricular fibrillation
- Severe aortic or mitral valve disease
- Known malfunctioning artificial heart valve
- Uncorrected obstructive valvular disease
- Hypertrophic cardiomyopathy
Show all 15Show fewer
- Fertile women
- Uncorrected thyroid disease
- Presence of any disease/condition that might per se influence exercise performance
- Left ventricular assist device
- Pacemaker-guided heart rate at rest or during exercise
- Known contraindication for treatment with levosimendan
- Any treatment with levosimendan in the previous 6 months
- Inability to perform a VO2max test
- Symptomatic hypotension or systolic blood pressure < 90 mmHg
Trial locations and contacts
3 sites in 1 country.
Denmark3 sites, 3 recruiting
- Recruiting
Department of Cardiology, The Heart Center, Copenhagen University Hospital, Rigshospitalet
Copenhagen, DK-2100
Finn Gustafsson, MD, professor, PhD, DMSci, +45 35459743, finng@dadlnet.dk
Lærke Nelson, MD, +45 35459549, laerke.marie.nelson@regionh.dk
- Recruiting
Department of Cardiology, Copenhagen University Hospital, Herlev and Gentofte Hospital, Herlev, Denmark
Herlev, DK-2730
Morten Schou, MD, PhD, +45 40523920, schou@dadlnet.dk
Morten Schou, MD, PhD
- Recruiting
Department of Cardiology, Odense University Hospital, Odense, Denmark
Odense, DK-5000
Jacob E Møller, MD, professor, PhD, DMSci, +45 51439630, jem@dadlnet.do
Mikael K Poulsen, MD, PhD, +45 24798402, mikael.kjaer.poulsen1@rsyd.dk
About this study
Official title: Effect of Levosimendan or Placebo on Exercise Capacity and Hemodynamics in Patients With Advanced Chronic Heart Failure (LOCO-CHF Trial)
Purpose: This study evaluates the subacute effect of levosimendan infusion on exercise capacity and exercise hemodynamics compared with placebo in patients with advanced chronic heart failure.
Hypothesis: Treatment with 6 hours infusion of levosimendan compared with placebo improves exercise capacity and exercise hemodynamics evaluated by change in CO/PCWP.
Design: The study is a prospective multi-center, double-blinded, placebo controlled randomized study. 42 consecutive patients who meet the eligibility criteria will be enrolled.
Read the detailed description
Background: Patients with advanced heart failure (HF) symptoms (NYHA III-IV) have poor quality of life and significantly impaired functional capacity despite optimal medical management. Exercise intolerance in HF results from multiple pathophysiological processes, but central hemodynamics during exercise are important determinants. In patients with advanced HF, intermittent levosimendan infusion is sometimes used to relieve symptoms and possibly improve prognosis. A short-term effect of levosimendan infusion on exercise capacity has previously been reported. However, the underlying mechanisms behind such an improvement, as well as more durable effects of levosimendan on exercise capacity in advanced chronic HF, have not been clearly established. Also the hemodynamic effect of levosimendan has not been investigated in advanced chronic HF during exercise.
To our knowledge no previous studies have evaluated the subacute effect of levosimendan infusion on exercise capacity and exercise hemodynamics in patients with advanced chronic HF. This study will hopefully improve the understanding of the role of levosimendan in the management of these patients.
Purpose: This study evaluates the subacute effect of levosimendan infusion on exercise capacity and exercise hemodynamics compared with placebo in patients with advanced chronic HF.
Hypothesis: Treatment with 6 hours infusion of levosimendan 0.2 µg/kg/min compared with placebo improves exercise capacity and exercise hemodynamics evaluated by change in CO/PCWP (Day 0 to Day 5 (4-6) after infusion) in patients with advanced chronic HF.
Design: The study is a prospective multi-center, double-blinded, placebo controlled randomized study. The study population will consist of 42 consecutive patients who meet the eligibility criteria. Patients will be randomized 1:1 to treatment with either levosimendan or placebo.
- Conditions
- Heart Failure
- Being tested
- Levosimendan, Placebo
- Keywords
- Advanced chronic heart failure, Exercise capacity, Exercise hemodynamics, Levosimendan
- Medical subject headings
- Heart Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LevosimendanDrug
Also called Simdax
Levosimendan, 2.5 mg/mL concentrate for dilution. 5 mL of the study drug will be injected into a 245 mL isotonic glucose solution.
Patients will receive a 6 hours infusion of this study drug at an infusion rate of 0.2 µg/kg/min.
PlaceboDrug
The placebo solution will be prepared by adding 10 mL of 5% dextrose to a vial containing Soluvit (vitamin B) under aseptical conditions. 5 mL of this solution is then added to 245 mL of isotonic sodium chloride solution.
5% dextrose and vitamin B are added to ensure yellow coloring indistinguishable from the active drug (levosimendan).
Patients will receive a 6 hours infusion of this study drug. Infusion rate will be calculated in similar fashion to the levosimendan group.
| Study group | Role | What they receive |
|---|---|---|
| Levosimendan | Active comparator | Study participants in this arm will receive a 6 hours infusion of levosimendan 0.2 µg/kg/min. Receives: Drug: Levosimendan |
| Placebo | Placebo comparator | Study participants in this arm will receive a 6 hours infusion of placebo (sterile isotonic sodium chloride + 5% dextrose + vitamin B) Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
ΔCO/PCWP (submax)
Change in CO/PCWP from Day 0 (infusion of study medication) to Day 5 (day 4-6) at the workload corresponding to 50% of pVO2 determined at baseline
Measured: Day 0 to Day 5 (4-6)
Secondary outcomes (21)
ΔCO/PCWP (peak)
Change in CO/PCWP from Day 0 (infusion of study medication) to Day 5 (day 4-6) at peak exercise
Measured: Day 0 to Day 5 (4-6)
ΔCO (peak)
Change in maximal CO from Day 0 (infusion of study medication) to Day 5 (day 4-6) at peak exercise
Measured: Day 0 to Day 5 (4-6)
ΔPCWP (peak)
Change in PCWP from Day 0 (infusion of study medication) to Day 5 (day 4-6) at the maximal load obtained during both invasive measurements
Measured: Day 0 to Day 5 (4-6)
CO maximal
Maximal CO at Day 5 (day 4-6)
Measured: Day 5
PCWP maximal
Maximal PCWP at Day 5 (day 4-6)
Measured: Day 5
SvO2 maximal
Maximal SvO2 at Day 5 (day 4-6)
Measured: Day 5
Workload maximal
Maximal workload (watt) at Day 5 (day 4-6)
Measured: Day 5
ΔPCWP (rest)
Change in resting PCWP from Day 0 (infusion of study medication) to Day 5 (day 4-6)
Measured: Day 0 to Day 5 (4-6)
ΔCO (rest)
Change in resting CO from Day 0 (infusion of study medication) to Day 5 (day 4-6)
Measured: Day 0 to Day 5 (4-6)
ΔCVP (rest)
Change in resting CVP from Day 0 (infusion of study medication) to Day 5 (day 4-6)
Measured: Day 0 to Day 5 (4-6)
ΔmPA (rest)
Change in resting mPA from Day 0 (infusion of study medication) to Day 5 (day 4-6)
Measured: Day 0 to Day 5 (4-6)
ΔSvO2 (rest)
Change in resting SvO2 from Day 0 (infusion of study medication) to Day 5 (day 4-6)
Measured: Day 0 to Day 5 (4-6)
Δ6MWT day 3
Change in 6MWT from Day 0 (infusion of study medication) to Day 3
Measured: Day 0 to Day 3
Δ6MWT day 5 (4-6)
Change in 6MWT from Day 0 (infusion of study medication) to Day 5 (day 4-6)
Measured: Day 0 to Day 5 (day 4-6)
Δ6MWT day 14
Change in 6MWT from Day 0 (infusion of study medication) to Day 14
Measured: Day 0 to Day 14
ΔNT-proBNP day 3
Change in NT-proBNP from Day 0 (infusion of study medication) to Day 3
Measured: Day 0 to Day 3
ΔNT-proBNP day 5
Change in NT-proBNP from Day 0 (infusion of study medication) to Day 5 (day 4-6)
Measured: Day 0 to Day 5 (day 4-6)
ΔNT-proBNP day 14
Change in NT-proBNP from Day 0 (infusion of study medication) to Day 14
Measured: Day 0 to Day 14
QOL day 3
Quality of life (QOL) score using the Kansas City Cardiomyopathy Questionnaire (KCCQ) at Day 3 after infusion of study medication
Measured: Day 3
QOL day 5
Quality of life (QOL) score using the Kansas City Cardiomyopathy Questionnaire (KCCQ) at Day 5 (4-6) after infusion of study medication
Measured: Day 5
QOL Day 14
Quality of life (QOL) score using the Kansas City Cardiomyopathy Questionnaire (KCCQ) at Day 14 after infusion of study medication
Measured: Day 14
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Jul 2018
- Study start1 Aug 2019 (estimated)
- Primary completion1 Jul 2020 (estimated)
- Study completion30 Jul 2020 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Heart FailureStudies of the same condition, open and under way.
- 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
- This is a prospective multi-center, double-blinded, placebo controlled, randomized study in patients with advanced chronic heart failure. Patients who meet the eligibility criteria will be randomized in a 1:1 ratio for treatment with 6 hours infusion of either (i) levosimendan 0.2 µg/kg/min or (ii) placebo (sterile 5% dextrose). At baseline an upright ergometer maximal exercise test is performed to determine max workload and pVO2 (Test 0). Based on this test 50% of pVO2 with corresponding workload (watt) is calculated (submax). At Day 0 patients will perform a supine ergometer maximal exercise test (Test 1) with simultaneous invasive hemodynamic measurement by Swan-Ganz catheter. Subsequently, patients will receive 6 hours infusion of study medication. At Day 5 (4-6 days after infusion of study medication) patients will repeat the supine ergometer maximal exercise test (Test 2) with simultaneous invasive hemodynamic measurements.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 42 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Finn Gustafsson
- Sponsor type
- University, hospital or other
- Collaborators
- Orion Corporation, Orion Pharma
- Responsible party
- Sponsor-investigator, Finn Gustafsson, Copenhagen University Hospital, Rigshospitalet
- Investigators
- Finn Gustafsson, MD, professor, PhD, DMSci, Principal investigator, Department of Cardiology, The Heart Center, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03576677
- Sponsor's protocol ID
- RH-HJE-LN-02
- Acronym
- LOCO-CHF
- Status last verified
- Jul 2019
- First submitted
- 11 Jun 2018
- Last updated
- 17 Jul 2019
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 Jul 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Levosimendan or Placebo on Exercise Capacity and Hemodynamics in Patients With Advanced Chronic Heart Failure (LOCO-CHF Trial)
- ClinicalTrials.gov ID
- NCT03576677
- Acronym / sponsor ID
- LOCO-CHF / RH-HJE-LN-02
- Conditions
- Heart Failure
- Keywords
- Advanced chronic heart failure, Exercise capacity, Exercise hemodynamics, Levosimendan
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 42 participants (estimated)
- Lead sponsor
- Finn GustafssonUniversity, hospital or other
- Collaborators
- Orion Corporation, Orion Pharma
- Study start
- 1 Aug 2019 (estimated)
- Primary completion
- 1 Jul 2020 (estimated)
- Study completion
- 30 Jul 2020 (estimated)
- First posted
- 3 Jul 2018 (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.
Purpose: This study evaluates the subacute effect of levosimendan infusion on exercise capacity and exercise hemodynamics compared with placebo in patients with advanced chronic heart failure.
Hypothesis: Treatment with 6 hours infusion of levosimendan compared with placebo improves exercise capacity and exercise hemodynamics evaluated by change in CO/PCWP.
Design: The study is a prospective multi-center, double-blinded, placebo controlled randomized study. 42 consecutive patients who meet the eligibility criteria will be enrolled.
Detailed description
Background: Patients with advanced heart failure (HF) symptoms (NYHA III-IV) have poor quality of life and significantly impaired functional capacity despite optimal medical management. Exercise intolerance in HF results from multiple pathophysiological processes, but central hemodynamics during exercise are important determinants. In patients with advanced HF, intermittent levosimendan infusion is sometimes used to relieve symptoms and possibly improve prognosis. A short-term effect of levosimendan infusion on exercise capacity has previously been reported. However, the underlying mechanisms behind such an improvement, as well as more durable effects of levosimendan on exercise capacity in advanced chronic HF, have not been clearly established. Also the hemodynamic effect of levosimendan has not been investigated in advanced chronic HF during exercise.
To our knowledge no previous studies have evaluated the subacute effect of levosimendan infusion on exercise capacity and exercise hemodynamics in patients with advanced chronic HF. This study will hopefully improve the understanding of the role of levosimendan in the management of these patients.
Purpose: This study evaluates the subacute effect of levosimendan infusion on exercise capacity and exercise hemodynamics compared with placebo in patients with advanced chronic HF.
Hypothesis: Treatment with 6 hours infusion of levosimendan 0.2 µg/kg/min compared with placebo improves exercise capacity and exercise hemodynamics evaluated by change in CO/PCWP (Day 0 to Day 5 (4-6) after infusion) in patients with advanced chronic HF.
Design: The study is a prospective multi-center, double-blinded, placebo controlled randomized study. The study population will consist of 42 consecutive patients who meet the eligibility criteria. Patients will be randomized 1:1 to treatment with either levosimendan or placebo.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- This is a prospective multi-center, double-blinded, placebo controlled, randomized study in patients with advanced chronic heart failure. Patients who meet the eligibility criteria will be randomized in a 1:1 ratio for treatment with 6 hours infusion of either (i) levosimendan 0.2 µg/kg/min or (ii) placebo (sterile 5% dextrose). At baseline an upright ergometer maximal exercise test is performed to determine max workload and pVO2 (Test 0). Based on this test 50% of pVO2 with corresponding workload (watt) is calculated (submax). At Day 0 patients will perform a supine ergometer maximal exercise test (Test 1) with simultaneous invasive hemodynamic measurement by Swan-Ganz catheter. Subsequently, patients will receive 6 hours infusion of study medication. At Day 5 (4-6 days after infusion of study medication) patients will repeat the supine ergometer maximal exercise test (Test 2) with simultaneous invasive hemodynamic measurements.
| Arm | Type | Receives |
|---|---|---|
| Levosimendan | Active comparator | Drug: LevosimendanStudy participants in this arm will receive a 6 hours infusion of levosimendan 0.2 µg/kg/min. |
| Placebo | Placebo comparator | Drug: PlaceboStudy participants in this arm will receive a 6 hours infusion of placebo (sterile isotonic sodium chloride + 5% dextrose + vitamin B) |
Who may qualify
- Ages
- 18 to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Age ≥18 years
- NYHA III-IV on optimal medical treatment
- LVEF ≤35%
- NT-proBNP >600 µg/L
- pVO2 <20 mL/kg/min
Key exclusion criteria (15 listed)
- Recent or acute coronary and respiratory syndromes
- Recent sustained ventricular tachycardia or ventricular fibrillation
- Severe aortic or mitral valve disease
- Known malfunctioning artificial heart valve
- Uncorrected obstructive valvular disease
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 |
|---|---|---|
| LevosimendanAlso: SimdaxLevosimendan, 2.5 mg/mL concentrate for dilution. 5 mL of the study drug will be injected into a 245 mL isotonic glucose solution. Patients will receive a 6 hours infusion of this study drug at an infusion rate of 0.2 µg/kg/min. | Drug | Levosimendan |
| PlaceboThe placebo solution will be prepared by adding 10 mL of 5% dextrose to a vial containing Soluvit (vitamin B) under aseptical conditions. 5 mL of this solution is then added to 245 mL of isotonic sodium chloride solution. 5% dextrose and vitamin B are added to ensure yellow coloring indistinguishable from the active drug (levosimendan). Patients will receive a 6 hours infusion of this study drug. Infusion rate will be calculated in similar fashion to the levosimendan group. | Drug | Placebo |
Primary outcome
ΔCO/PCWP (submax)
Time frame: Day 0 to Day 5 (4-6)
Change in CO/PCWP from Day 0 (infusion of study medication) to Day 5 (day 4-6) at the workload corresponding to 50% of pVO2 determined at baseline
21 secondary outcomes
ΔCO/PCWP (peak)
Time frame: Day 0 to Day 5 (4-6)
ΔCO (peak)
Time frame: Day 0 to Day 5 (4-6)
ΔPCWP (peak)
Time frame: Day 0 to Day 5 (4-6)
CO maximal
Time frame: Day 5
PCWP maximal
Time frame: Day 5
SvO2 maximal
Time frame: Day 5
Workload maximal
Time frame: Day 5
ΔPCWP (rest)
Time frame: Day 0 to Day 5 (4-6)
ΔCO (rest)
Time frame: Day 0 to Day 5 (4-6)
ΔCVP (rest)
Time frame: Day 0 to Day 5 (4-6)
ΔmPA (rest)
Time frame: Day 0 to Day 5 (4-6)
ΔSvO2 (rest)
Time frame: Day 0 to Day 5 (4-6)
Δ6MWT day 3
Time frame: Day 0 to Day 3
Δ6MWT day 5 (4-6)
Time frame: Day 0 to Day 5 (day 4-6)
Δ6MWT day 14
Time frame: Day 0 to Day 14
ΔNT-proBNP day 3
Time frame: Day 0 to Day 3
ΔNT-proBNP day 5
Time frame: Day 0 to Day 5 (day 4-6)
ΔNT-proBNP day 14
Time frame: Day 0 to Day 14
QOL day 3
Time frame: Day 3
QOL day 5
Time frame: Day 5
QOL Day 14
Time frame: Day 14
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Jul 2019.
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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. This study is not recruiting at the moment.
Finn Gustafsson, MD, professor, PhD, DMSci principal investigator
Department of Cardiology, The Heart Center, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
3 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 Levosimendan in people with Heart Failure, run by Finn Gustafsson at 3 sites in Denmark.
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 15 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: status not confirmed, as of the sponsor's last update on 17 Jul 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Denmark. 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 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Finn Gustafsson, MD, professor, PhD, DMSci (+45 35459743, finng@dadlnet.dk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
ΔCO/PCWP (submax) (time frame: Day 0 to Day 5 (4-6)). 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 17 Jul 2019.