Study NCT03541603
Hemodynamic Evaluation of Levosimendan in Patients With PH-HFpEF (HELP)
Submitted Date:  April 29, 2021 (v19)
Quality Control Review Has Not Concluded

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Open or close this module Study Identification
Unique Protocol ID: TNX-LVO-04
Brief Title: Hemodynamic Evaluation of Levosimendan in Patients With PH-HFpEF (HELP)
Official Title: A Double-Blind, Randomized, Placebo-Controlled Study of Levosimendan in Pulmonary Hypertension Patients With Heart Failure and Preserved Left Ventricular Ejection Fraction (PH-HFpEF)
Secondary IDs:
Open or close this module Study Status
Record Verification: April 2020
Overall Status: Completed
Study Start: November 14, 2018
Primary Completion: April 7, 2020 [Actual]
Study Completion: April 7, 2020 [Actual]
First Submitted: May 3, 2018
First Submitted that
Met QC Criteria:
May 17, 2018
First Posted: May 30, 2018 [Actual]
Results First Submitted: April 29, 2021
Results First Submitted that
Met QC Criteria:
Results First Posted: May 21, 2021 [Actual]
Last Update Submitted that
Met QC Criteria:
Last Update Posted: May 21, 2021 [Actual]
Open or close this module Sponsor/Collaborators
Sponsor: Tenax Therapeutics, Inc.
Responsible Party: Sponsor
Collaborators:
Open or close this module Oversight
U.S. FDA-regulated Drug: Yes
U.S. FDA-regulated Device: No
Data Monitoring: No
Open or close this module Study Description
Brief Summary: Phase 2 study to evaluate the efficacy and safety of intermittent levosimendan compared with placebo in hemodynamic improvement with exercise in PH-HFpEF subjects
Detailed Description: Levosimendan and its prolonged active metabolite, OR-1896, have been shown to have favorable hemodynamic effects in subjects with pulmonary hypertension and right heart failure. Clinical studies that have been conducted in subjects with right heart failure and pulmonary hypertension suggest levosimendan may be an effective therapy in treatment of subjects with PH-HFpEF. This study will provide demonstration of levosimendan/OR-1896's effectiveness in critical measures of hemodynamic response in weekly administration of levosimendan and the concomitant response as measured by exercise capacity, subject quality of life, and changes in functional capacity. These data will support and guide the Phase 3 development of levosimendan in PH-HFpEF subjects.
Open or close this module Conditions
Conditions: Hypertension Pulmonary Secondary
Heart Failure, Right Sided
Heart Failure With Normal Ejection Fraction
Keywords: PH-HFpEF
Open or close this module Study Design
Study Type: Interventional
Primary Purpose: Treatment
Study Phase: Phase 2
Interventional Study Model: Parallel Assignment
Number of Arms: 2
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Allocation: Randomized
Enrollment: 44 [Actual]
Open or close this module Arms and Interventions
Arms Assigned Interventions
Experimental: Levosimendan 2.5mg/mL Injectable Solution
0.075 - 0.1µg/kg/min for 24 hrs (weekly)
Drug: Levosimendan
A sterile 2.5 mg/mL concentrate solution that is diluted in 5% Dextrose or 0.9 Normal Saline to achieve a 50 microgram/min solution for infusion
Other Names:
  • Levosimendan 2.5 mg/mL Injectable Solution
Placebo Comparator: Matching Placebo
0.075 - 0.1µg/kg/min for 24 hrs (weekly)
Drug: Matching Placebo
A sterile 2.5mg/mL concentrate solution that is diluted in 5% Dextrose or 0.9 Normal Saline to achieve a 50 microgram/min solution for infusion
Other Names:
  • Placebo
Open or close this module Outcome Measures
[See Results Section.]
Primary Outcome Measures:
1. Change From Baseline Pulmonary Capillary Wedge Pressure (PCWP) With Bicycle Exercise
[ Time Frame: Week 6 ]

Change from baseline Pulmonary Capillary Wedge Pressure (PCWP) with bicycle exercise at Week 6
Secondary Outcome Measures:
1. Change in Cardiac Index (CI) at Rest and With Exercise
[ Time Frame: Week 6 ]

Change in Cardiac Index (CI) at rest and with exercise at Week 6
2. Change in Pulmonary Vascular Resistance (PVR) Effect at Rest and With Exercise
[ Time Frame: Week 6 ]

Change in Pulmonary Vascular Resistance (PVR) effect at rest and with exercise at Week 6
3. Change in PCWP When Supine and Legs Elevated
[ Time Frame: Week 6 ]

4. Patient Global Assessment
[ Time Frame: Week 6 ]

Patient assessment of well-being based on 6 questions assessed on a 5-point Likert Scale ( 1 =worst, 5= best) (no comparison to baseline as no instrument used at baseline)
5. Exercise Duration Via 6 Minute Walk Test
[ Time Frame: Week 6 ]

Change in 6-minute walk test at Week 6 vs baseline
6. Physician's Assessment of Functional Class
[ Time Frame: Week 6 ]

Physician's Assessment of New York Heart Association (NYHA) Classification (one of four categories based on how much the patient is limited during physical activity. (Class I, no limitation of physical activity to Class IV, marked limitation of physical activity).
7. Composite Incidence of Death or Hospitalization
[ Time Frame: Week 6 ]

Composite incidence of death or hospitalization through Week 6
Open or close this module Eligibility
Minimum Age: 18 Years
Maximum Age:
Sex: All
Gender Based:
Accepts Healthy Volunteers: No
Criteria:

Inclusion Criteria:

Criteria to enter Open-label, Lead-in Dose Phase:

  • Diagnosis of WHO Group 2 Pulmonary Hypertension (PH) with heart failure and preserved ejection fraction (HFpEF) confirmed at the time of the diagnosis of pulmonary hypertension.
  • Baseline Pulmonary Arterial Pressure (PAP) ≥35, PCWP ≥20, NYHA Class IIb/III, Left Ventricular Ejection Fraction (LVEF) ≥40%
  • Ability to walk at least 50 meters, but not more than 550 meters in a six-minute walk test.
  • Stable oxygen treatment (if applicable), and medications for heart failure, hypertension and respiratory condition

Criterion for Randomization to Double-blind Phase:

  • Response to Open-label, Lead-in Levosimendan: Patients who demonstrate a ≥4mmHg reduction in PCWP from baseline measured at bicycle exercise (25 watts) with no more than a 10% decrease from baseline in cardiac index

Exclusion Criteria:

  • Subject has primary diagnosis of PH other than Group 2 PH-HFpEF
  • Previous Percutaneous Coronary Intervention (PCI) or cardiac surgery (CABG) , unless they have a negative stress test in last 12 months)
  • Congenital heart disease
  • Clinically significant lung disease
  • Planned heart or lung surgery
  • Cardiac Index >4.0 L/min/m2
  • Concomitant administration of pulmonary vasodilator therapy or taken within 14 days
  • Dialysis or Glomerular Filtration Rate (GFR) <30 mL/min/1.73 m2
  • Liver dysfunction with Child Pugh Class B or C
  • Evidence of systemic infection
  • Weight > 150kg
  • Symptomatic systolic blood pressure (SBP) cannot be managed to ensure SBP >100 mmHg
  • Heart rate >= 100 bpm with study drug, symptomatic and persistent for at least 10 minutes
  • Hemoglobin < 80 g/L
  • Serum potassium < 3.0 mmol/L or > 5.5 mmol/L at baseline
  • Patients having severely compromised immune function
  • Pregnant, suspected to be pregnant, or breast-feeding
Open or close this module Contacts/Locations
Locations: United States, California
Stanford Healthcare
Stanford, California, United States, 94305
United States, Illinois
Northwestern Memorial Hospital
Chicago, Illinois, United States, 60611
United States, Massachusetts
Tufts Medical Center
Boston, Massachusetts, United States, 02111
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Brigham and Women's Hospital
Boston, Massachusetts, United States, 02215
United States, Minnesota
University of Minnesota Medical Center
Minneapolis, Minnesota, United States, 55455
Mayo Clinic
Rochester, Minnesota, United States, 55905
United States, Nebraska
University of Nebraska Medical Center
Omaha, Nebraska, United States, 68198
United States, New York
North Shore University Hospital
Manhasset, New York, United States, 11030
New York Presbyterian Hospital-Weill Cornell Medicine
New York, New York, United States, 10021
Ichan School of Medicine at Mount Sinai
New York, New York, United States, 10029
United States, Ohio
Christ Hospital
Cincinnati, Ohio, United States, 45219
United States, Pennsylvania
Hospital of the University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
University of Pittsburgh Presbyterian Hospital
Pittsburgh, Pennsylvania, United States, 15213
United States, South Carolina
Medical University of South Carolina
Charleston, South Carolina, United States, 29425
United States, Wisconsin
UW Health University Hospital
Madison, Wisconsin, United States, 53792
Open or close this module IPDSharing
Plan to Share IPD: No
Open or close this module References
Links:
Available IPD/Information:
Open or close this module Document Section
Study Protocol
Document Date: May 14, 2019
Uploaded: 04/29/2021 09:22
File Name: Prot_000.pdf
Statistical Analysis Plan
Document Date: May 15, 2019
Uploaded: 04/29/2021 09:29
File Name: SAP_001.pdf

Quality Control Review Comment provided by the National Library of Medicine:

  1. Some information appears inappropriate where reported.
Study Results
Open or close this module Participant Flow
Recruitment Details

44 patients satisfied entry criteria for ewnrollment and received lead-in open-label levosimendan.

37 of the 44 enrolled patients achieved responder criteria following 24hr lead-in open label levosimendan infusion and were randomized to study

Pre-assignment Details
 
Arm/Group Title Levosimendan 2.5mg/mL Injectable Solution Matching Placebo
Arm/Group Description

0.075 - 0.1µg/kg/min for 24 hrs (weekly)

Levosimendan: A sterile 2.5 mg/mL concentrate solution that is diluted in 5% Dextrose or 0.9 Normal Saline to achieve a 50 microgram/min solution for infusion

0.075 - 0.1µg/kg/min for 24 hrs (weekly)

Matching Placebo: A sterile 2.5mg/mL concentrate solution that is diluted in 5% Dextrose or 0.9 Normal Saline to achieve a 50 microgram/min solution for infusion

Period Title: Overall Study
Started 18 19
Completed 18 17
Not Completed 0 2
Open or close this module Baseline Characteristics
Arm/Group TitleLevosimendan 2.5mg/mL Injectable SolutionMatching PlaceboTotal
Arm/Group Description

0.075 - 0.1µg/kg/min for 24 hrs (weekly)

Levosimendan: A sterile 2.5 mg/mL concentrate solution that is diluted in 5% Dextrose or 0.9 Normal Saline to achieve a 50 microgram/min solution for infusion

0.075 - 0.1µg/kg/min for 24 hrs (weekly)

Matching Placebo: A sterile 2.5mg/mL concentrate solution that is diluted in 5% Dextrose or 0.9 Normal Saline to achieve a 50 microgram/min solution for infusion

Total of all reporting groups
Overall Number of Baseline Participants 18 19 37
Baseline Analysis Population Description
Age, Continuous
Mean (Standard Deviation)
Unit of measure: years
Number Analyzed18 Participants19 Participants37 Participants
68.8(7.5)67.4(11.0)68.1(9.3)
Sex: Female, Male
Measure Type: Count of Participants
Unit of measure: Participants
Number Analyzed18 Participants19 Participants37 Participants
Female
10
55.56%
12
63.16%
22
59.46%
Male
8
44.44%
7
36.84%
15
40.54%
Race (NIH/OMB)
Measure Type: Count of Participants
Unit of measure: Participants
Number Analyzed18 Participants19 Participants37 Participants
American Indian or Alaska Native
1
5.56%
0
0%
1
2.7%
Asian
0
0%
0
0%
0
0%
Native Hawaiian or Other Pacific Islander
0
0%
0
0%
0
0%
Black or African American
1
5.56%
2
10.53%
3
8.11%
White
16
88.89%
17
89.47%
33
89.19%
More than one race
0
0%
0
0%
0
0%
Unknown or Not Reported
0
0%
0
0%
0
0%
Region of Enrollment
Measure Type: Number
Unit of measure: participants
Number Analyzed18 Participants19 Participants37 Participants
United States
181937
Open or close this module Outcome Measures
1. Primary Outcome:
Title Change From Baseline Pulmonary Capillary Wedge Pressure (PCWP) With Bicycle Exercise
Description Change from baseline Pulmonary Capillary Wedge Pressure (PCWP) with bicycle exercise at Week 6
Time Frame Week 6
Outcome Measure Data
Analysis Population Description
patients completing Week 6 visit
 
Arm/Group TitleLevosimendan 2.5mg/mL Injectable SolutionMatching Placebo
Arm/Group Description

0.075 - 0.1µg/kg/min for 24 hrs (weekly)

Levosimendan: A sterile 2.5 mg/mL concentrate solution that is diluted in 5% Dextrose or 0.9 Normal Saline to achieve a 50 microgram/min solution for infusion

0.075 - 0.1µg/kg/min for 24 hrs (weekly)

Matching Placebo: A sterile 2.5mg/mL concentrate solution that is diluted in 5% Dextrose or 0.9 Normal Saline to achieve a 50 microgram/min solution for infusion

Overall Number of Participants Analyzed18 17
Mean (Standard Deviation)
Unit of Measure: mmHg
-1.9(10.07) -0.5(7.87)
2. Secondary Outcome:
Title Change in Cardiac Index (CI) at Rest and With Exercise
Description Change in Cardiac Index (CI) at rest and with exercise at Week 6
Time Frame Week 6
Outcome Measure Data
Analysis Population Description
[Not Specified]
 
Arm/Group TitleLevosimendan 2.5mg/mL Injectable SolutionMatching Placebo
Arm/Group Description

0.075 - 0.1µg/kg/min for 24 hrs (weekly)

Levosimendan: A sterile 2.5 mg/mL concentrate solution that is diluted in 5% Dextrose or 0.9 Normal Saline to achieve a 50 microgram/min solution for infusion

0.075 - 0.1µg/kg/min for 24 hrs (weekly)

Matching Placebo: A sterile 2.5mg/mL concentrate solution that is diluted in 5% Dextrose or 0.9 Normal Saline to achieve a 50 microgram/min solution for infusion

Overall Number of Participants Analyzed18 17
Mean (Standard Deviation)
Unit of Measure: L/min/m2
rest
0.05(0.699) -0.15(0.262)
exercise
0.24(1.106) 0.04(0.594)
3. Secondary Outcome:
Title Change in Pulmonary Vascular Resistance (PVR) Effect at Rest and With Exercise
Description Change in Pulmonary Vascular Resistance (PVR) effect at rest and with exercise at Week 6
Time Frame Week 6
Outcome Measure Data
Analysis Population Description
[Not Specified]
 
Arm/Group TitleLevosimendan 2.5mg/mL Injectable SolutionMatching Placebo
Arm/Group Description

0.075 - 0.1µg/kg/min for 24 hrs (weekly)

Levosimendan: A sterile 2.5 mg/mL concentrate solution that is diluted in 5% Dextrose or 0.9 Normal Saline to achieve a 50 microgram/min solution for infusion

0.075 - 0.1µg/kg/min for 24 hrs (weekly)

Matching Placebo: A sterile 2.5mg/mL concentrate solution that is diluted in 5% Dextrose or 0.9 Normal Saline to achieve a 50 microgram/min solution for infusion

Overall Number of Participants Analyzed18 17
Mean (Standard Deviation)
Unit of Measure: mmHg.min/L
rest
-0.09(1.050) 0.15(2.238)
exercise
-0.44(1.539) -0.16(1.81)
4. Secondary Outcome:
Title Change in PCWP When Supine and Legs Elevated
Description
Time Frame Week 6
Outcome Measure Data
Analysis Population Description
Change in PCWP at rest and legs elevated at Week 6
 
Arm/Group TitleLevosimendan 2.5mg/mL Injectable SolutionMatching Placebo
Arm/Group Description

0.075 - 0.1µg/kg/min for 24 hrs (weekly)

Levosimendan: A sterile 2.5 mg/mL concentrate solution that is diluted in 5% Dextrose or 0.9 Normal Saline to achieve a 50 microgram/min solution for infusion

0.075 - 0.1µg/kg/min for 24 hrs (weekly)

Matching Placebo: A sterile 2.5mg/mL concentrate solution that is diluted in 5% Dextrose or 0.9 Normal Saline to achieve a 50 microgram/min solution for infusion

Overall Number of Participants Analyzed17 17
Mean (Standard Deviation)
Unit of Measure: mmHg
rest
-5.1(5.42) -1.7(6.14)
legs elevated
-6.2(7.92) -0.3(5.45)
5. Secondary Outcome:
Title Patient Global Assessment
Description Patient assessment of well-being based on 6 questions assessed on a 5-point Likert Scale ( 1 =worst, 5= best) (no comparison to baseline as no instrument used at baseline)
Time Frame Week 6
Outcome Measure Data
Analysis Population Description
[Not Specified]
 
Arm/Group TitleLevosimendan 2.5mg/mL Injectable SolutionMatching Placebo
Arm/Group Description

0.075 - 0.1µg/kg/min for 24 hrs (weekly)

Levosimendan: A sterile 2.5 mg/mL concentrate solution that is diluted in 5% Dextrose or 0.9 Normal Saline to achieve a 50 microgram/min solution for infusion

0.075 - 0.1µg/kg/min for 24 hrs (weekly)

Matching Placebo: A sterile 2.5mg/mL concentrate solution that is diluted in 5% Dextrose or 0.9 Normal Saline to achieve a 50 microgram/min solution for infusion

Overall Number of Participants Analyzed18 17
Median (Inter-Quartile Range)
Unit of Measure: units on a scale
3(3 to 4) 3(3 to 4)
6. Secondary Outcome:
Title Exercise Duration Via 6 Minute Walk Test
Description Change in 6-minute walk test at Week 6 vs baseline
Time Frame Week 6
Outcome Measure Data
Analysis Population Description
[Not Specified]
 
Arm/Group TitleLevosimendan 2.5mg/mL Injectable SolutionMatching Placebo
Arm/Group Description

0.075 - 0.1µg/kg/min for 24 hrs (weekly)

Levosimendan: A sterile 2.5 mg/mL concentrate solution that is diluted in 5% Dextrose or 0.9 Normal Saline to achieve a 50 microgram/min solution for infusion

0.075 - 0.1µg/kg/min for 24 hrs (weekly)

Matching Placebo: A sterile 2.5mg/mL concentrate solution that is diluted in 5% Dextrose or 0.9 Normal Saline to achieve a 50 microgram/min solution for infusion

Overall Number of Participants Analyzed18 17
Mean (Standard Deviation)
Unit of Measure: meters
16.6(40.03) -12.8(35.08)
7. Secondary Outcome:
Title Physician's Assessment of Functional Class
Description Physician's Assessment of New York Heart Association (NYHA) Classification (one of four categories based on how much the patient is limited during physical activity. (Class I, no limitation of physical activity to Class IV, marked limitation of physical activity).
Time Frame Week 6
Outcome Measure Data
Analysis Population Description
[Not Specified]
   
Arm/Group TitleLevosimendan 2.5mg/mL Injectable SolutionMatching Placebo
Arm/Group Description

0.075 - 0.1µg/kg/min for 24 hrs (weekly)

Levosimendan: A sterile 2.5 mg/mL concentrate solution that is diluted in 5% Dextrose or 0.9 Normal Saline to achieve a 50 microgram/min solution for infusion

0.075 - 0.1µg/kg/min for 24 hrs (weekly)

Matching Placebo: A sterile 2.5mg/mL concentrate solution that is diluted in 5% Dextrose or 0.9 Normal Saline to achieve a 50 microgram/min solution for infusion

Overall Number of Participants Analyzed18 17
Measure Type: Count of Participants
Unit of Measure: Participants
 
Baseline
Class I
0
0%
0
0%
Class II
2
11.1%
3
17.6%
Class III
16
88.9%
14
82.4%
Class IV
0
0%
0
0%
Week 6
Class I
0
0%
0
0%
Class II
8
44.4%
5
29.4%
Class III
10
55.6%
12
70.6%
Class IV
0
0%
0
0%
8. Secondary Outcome:
Title Composite Incidence of Death or Hospitalization
Description Composite incidence of death or hospitalization through Week 6
Time Frame Week 6
Outcome Measure Data
Analysis Population Description
[Not Specified]
 
Arm/Group TitleLevosimendan 2.5mg/mL Injectable SolutionMatching Placebo
Arm/Group Description

0.075 - 0.1µg/kg/min for 24 hrs (weekly)

Levosimendan: A sterile 2.5 mg/mL concentrate solution that is diluted in 5% Dextrose or 0.9 Normal Saline to achieve a 50 microgram/min solution for infusion

0.075 - 0.1µg/kg/min for 24 hrs (weekly)

Matching Placebo: A sterile 2.5mg/mL concentrate solution that is diluted in 5% Dextrose or 0.9 Normal Saline to achieve a 50 microgram/min solution for infusion

Overall Number of Participants Analyzed18 17
Measure Type: Count of Participants
Unit of Measure: Participants
3
16.7%
1
5.9%
Open or close this module Adverse Events
 
Time Frame 6 weeks
Adverse Event Reporting Description [Not specified]
 
Arm/Group Title Levosimendan 2.5mg/mL Injectable Solution Matching Placebo
Arm/Group Description

0.075 - 0.1µg/kg/min for 24 hrs (weekly)

Levosimendan: A sterile 2.5 mg/mL concentrate solution that is diluted in 5% Dextrose or 0.9 Normal Saline to achieve a 50 microgram/min solution for infusion

0.075 - 0.1µg/kg/min for 24 hrs (weekly)

Matching Placebo: A sterile 2.5mg/mL concentrate solution that is diluted in 5% Dextrose or 0.9 Normal Saline to achieve a 50 microgram/min solution for infusion

All-Cause Mortality
  Levosimendan 2.5mg/mL Injectable SolutionMatching Placebo
 Affected / At Risk (%)# Events Affected / At Risk (%)# Events
Total 0 / 18 (0%)0 / 18 (0%)
Serious Adverse Events
  Levosimendan 2.5mg/mL Injectable SolutionMatching Placebo
 Affected / At Risk (%)# Events Affected / At Risk (%)# Events
Total 3 / 18 (16.67%)1 / 18 (5.56%)
Cardiac disorders
Cardiac failure acute † A 2 / 18 (11.11%)20 / 18 (0%)0
Cardiogenic Shock † A 0 / 18 (0%)01 / 18 (5.56%)1
Right ventricular failure † A 0 / 18 (0%)01 / 18 (5.56%)1
Infections and infestations
Bacteremia † A 1 / 18 (5.56%)10 / 18 (0%)0
Device related infection † A [1] 1 / 18 (5.56%)10 / 18 (0%)0
Indicates events were collected by systematic assessment.
ATerm from vocabulary, MedDRA (21.0)
[1]PICC LINE INFECTION WITH DUE TO SAE PICC HOSPITALIZATION
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
  Levosimendan 2.5mg/mL Injectable SolutionMatching Placebo
 Affected / At Risk (%)# Events Affected / At Risk (%)# Events
Total 13 / 18 (72.22%)8 / 18 (44.44%)
Cardiac disorders
Cardiac failure acute ∗ A 2 / 18 (11.11%)21 / 18 (5.56%)1
Cardiogenic shock ∗ A 0 / 18 (0%)01 / 18 (5.56%)1
Extrasystoles ∗ A 1 / 18 (5.56%)10 / 18 (0%)0
Palpitations ∗ A 1 / 18 (5.56%)10 / 18 (0%)0
Right ventricular failure ∗ A 0 / 18 (0%)01 / 18 (5.56%)1
Tachycardia † A 0 / 18 (0%)01 / 18 (5.56%)1
Ventricular tachycardia † A 0 / 18 (0%)01 / 18 (5.56%)1
Eye disorders
Vison blurred ∗ A 1 / 18 (5.56%)10 / 18 (0%)0
Gastrointestinal disorders
Diarrhea ∗ A 1 / 18 (5.56%)10 / 18 (0%)0
Nausea ∗ A 1 / 18 (5.56%)10 / 18 (0%)0
General disorders
Chills ∗ A 1 / 18 (5.56%)11 / 18 (5.56%)1
Edema ∗ A 1 / 18 (5.56%)10 / 18 (0%)0
Fatigue ∗ A 1 / 18 (5.56%)12 / 18 (11.11%)2
Infusion site erythema ∗ A 1 / 18 (5.56%)10 / 18 (0%)0
Infusion site hemorrhage ∗ A 1 / 18 (5.56%)11 / 18 (5.56%)1
Peripheral swelling ∗ A 1 / 18 (5.56%)10 / 18 (0%)0
Pyrexia ∗ A 1 / 18 (5.56%)10 / 18 (0%)0
Infections and infestations
Atypical pneumonia ∗ A 0 / 18 (0%)01 / 18 (5.56%)1
Bacteremia ∗ A 1 / 18 (5.56%)10 / 18 (0%)0
Bronchitis viral ∗ A 0 / 18 (0%)01 / 18 (5.56%)1
Cellulitis ∗ A 1 / 18 (5.56%)11 / 18 (5.56%)1
Device-related infection ∗ A 1 / 18 (5.56%)10 / 18 (0%)0
Influenza ∗ A 1 / 18 (5.56%)10 / 18 (0%)0
Tooth abscess ∗ A 1 / 18 (5.56%)10 / 18 (0%)0
Injury, poisoning and procedural complications
Accidental overdose ∗ A 1 / 18 (5.56%)10 / 18 (0%)0
Overdose ∗ A 1 / 18 (5.56%)10 / 18 (0%)0
Underdose ∗ A 0 / 18 (0%)01 / 18 (5.56%)1
Vascular access site pain ∗ A 0 / 18 (0%)02 / 18 (11.11%)2
Investigations
Blood creatinine increased ∗ A 1 / 18 (5.56%)10 / 18 (0%)0
Body temperature increased ∗ A 1 / 18 (5.56%)10 / 18 (0%)0
Heart rate increased † A 2 / 18 (11.11%)20 / 18 (0%)0
Metabolism and nutrition disorders
Hypokalemia ∗ A 2 / 18 (11.11%)21 / 18 (5.56%)1
Hypomagnesemia ∗ A 0 / 18 (0%)01 / 18 (5.56%)1
Lactic acidosis ∗ A 0 / 18 (0%)01 / 18 (5.56%)1
Musculoskeletal and connective tissue disorders
Arthralgia ∗ A 1 / 18 (5.56%)10 / 18 (0%)0
Muscle spasms ∗ A 2 / 18 (11.11%)20 / 18 (0%)0
Pain in extremity ∗ A 0 / 18 (0%)01 / 18 (5.56%)1
Nervous system disorders
Balance disorder ∗ A 1 / 18 (5.56%)10 / 18 (0%)0
Dizziness ∗ A 1 / 18 (5.56%)10 / 18 (0%)0
Dizziness postural ∗ A 0 / 18 (0%)01 / 18 (5.56%)1
Headache ∗ A 3 / 18 (16.67%)31 / 18 (5.56%)1
Product Issues
Device dislocation ∗ A 1 / 18 (5.56%)10 / 18 (0%)0
Device infusion issue ∗ A 1 / 18 (5.56%)11 / 18 (5.56%)1
Device occlusion ∗ A 0 / 18 (0%)01 / 18 (5.56%)1
Psychiatric disorders
Delirium ∗ A 0 / 18 (0%)01 / 18 (5.56%)1
Renal and urinary disorders
Acute kidney injury ∗ A 0 / 18 (0%)01 / 18 (5.56%)1
Respiratory, thoracic and mediastinal disorders
Asthma ∗ A 1 / 18 (5.56%)10 / 18 (0%)0
Cough ∗ A 0 / 18 (0%)01 / 18 (5.56%)1
Dyspnea ∗ A 2 / 18 (11.11%)21 / 18 (5.56%)1
Skin and subcutaneous tissue disorders
Alopecia ∗ A 0 / 18 (0%)01 / 18 (5.56%)1
Blister ∗ A 0 / 18 (0%)01 / 18 (5.56%)1
Dry skin ∗ A 0 / 18 (0%)01 / 18 (5.56%)1
Skin necrosis ∗ A 0 / 18 (0%)01 / 18 (5.56%)1
Vascular disorders
Peripheral artery stenosis ∗ A 0 / 18 (0%)01 / 18 (5.56%)1
Thrombophlebitis ∗ A 1 / 18 (5.56%)10 / 18 (0%)0
Venous thrombosis limb ∗ A 1 / 18 (5.56%)10 / 18 (0%)0
Indicates events were collected by systematic assessment.
Indicates events were collected by non-systematic methods.
ATerm from vocabulary, MedDRA (21.0)
Open or close this module Limitations and Caveats

Hemodynamic effects at Wk6 were measured ~1 week after final levosimendan infusion. Thus, hemodynamic effects at 6 weeks represent effects at trough levels; greater effects might have been observed with earlier assessment.

No previous study evaluated chronic levosimendan in PH-HFpEF. Chose a low dose out of an abundance of caution. It remains possible that higher doses may be more effective in selected patients.

Open or close this module More Information
Certain Agreements:
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact:
Name/Official Title:
Stuart Rich, MD; Chief Medical Officer
Organization:
Tenax Therapeutics, Inc.
Phone:
919 855 2100
Email:
s.rich@tenaxthera.com

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