Evaluation of the Safety and Effectiveness of the OPTIMIZER System in Subjects With Heart Failure: FIX-HF-5

• Sponsor: Impulse Dynamics (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00112125
• Collaborator: (none)
• Enrollment: 428
• Location: 1
• Arms: 2
• Actual Duration (Months): 169.5
• Patients Per Site Per Month: 2.5

Study Details

Study Description

Brief Summary

The purpose of this study is to determine whether treatment with the OPTIMIZER System is safe and effective in patients with moderate to severe heart failure symptoms.

Condition or Disease	Intervention/Treatment	Phase
Heart Failure, Congestive	Device: OPTIMIZER System	N/A

Detailed Description

IMPULSE Dynamics' FIX HF 5 US Study is a prospective, multi-center, study to evaluate the safety and efficacy of cardiac contractility modulation (CCM) signals delivered by the implantable OPTIMIZER™ System in patients with NYHA class III/IV heart failure. The study will involve the recruitment of approximately 420 subjects at a total of up to 50 sites nationwide.

Those subjects who fulfill all inclusion and exclusion criteria based upon baseline test results will be randomized to receive the OPTIMIZER™ System or to a control group. All subjects randomized will be followed for 1 year and shall receive the same study related assessments throughout the course of the study. In addition, all subjects will continue to receive optimal medical therapy for the treatment of their heart failure.

The primary efficacy assessment consists of a change in exercise tolerance measured by cardiopulmonary exercise testing at baseline and 6 months. Safety variables, such as the rate and cause of hospitalizations or death, shall be collected in both groups and shall be compared at 12 months.

Study Design

• Study Type: Interventional
• Actual Enrollment: 428 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Evaluation of the Safety and Efficacy of the OPTIMIZER System With Active Fixation Leads in Subjects With Heart Failure Resulting From Systolic Dysfunction: FIX-HF-5
• Actual Study Start Date: Feb 1, 2005
• Actual Primary Completion Date: Mar 19, 2019
• Actual Study Completion Date: Mar 19, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Optimizer System + Optimal medical treatment Optimizer System implanted and cardiac contractility modulation therapy activated.	Device: OPTIMIZER System
No Intervention: Optimal medical treatment Treatment with optimal medical therapy only.

Outcome Measures

Primary Outcome Measures

1. Efficacy Endpoint: Ventilatory Anerobic Threshold (VAT) [24 weeks]

   Number of participants with improvement in exercise tolerance at 24 weeks compared to baseline, as quantified by VO2 at ventilatory anerobic threshold (VAT) measured on cardiopulmonary exercise stress testing (CPX), and evaluated by a blinded core lab. Note: An individual subject is considered a responder if VAT increases by ≥20% at 24 weeks compared to their respective baseline value.

2. Safety Endpoint: Composite All-cause Mortality and All-cause Hospitalizations [50-weeks]

   The proportion of patients experiencing a composite event of all-cause mortality and all-cause hospitalizations evaluated at 50-weeks

Secondary Outcome Measures

1. Peak VO2 [24 weeks]

   Number of participants with improvement in peak VO2 measured on cardiopulmonary exercise stress testing (CPX), and evaluated by a blinded core lab. Note: An individual subject is considered a responder if peak VO2 increases by ≥20% at 24 weeks compared to their respective baseline value.

2. New York Heart Association (NYHA) Functional Classification [24 weeks]

   Number of participants with improvement in heart failure symptoms as quantified by a blinded clinician using the New York Heart Association (NYHA) functional classification at 24 weeks compared to baseline. The NYHA Class ranges from I - IV, with a lower class indicating a better status. Note: An individual subject is considered a responder if the NYHA class decreases by ≥ 1 at 24 weeks compared to their respective baseline class.

3. Minnesota Living With Heart Failure (MLWHF) Questionnaire [24 weeks]

   Number of subjects will improvement in quality of life at 24 weeks compared to baseline, as assessed by the Minnesota Living with Heart Failure (MLWHF) Questionnaire. The MLWHFQ score could range from 0 to 105, with higher scores indicating more significant impairment in health-related quality of life. Note: An individual subject is considered a responder if the MLWHFQ score decreases by ≥10 points at 24 weeks compared to their respective baseline score.

4. Six Minute Hall Walk (6MW) Test [24 weeks]

   Number of subjects with improvement in exercise tolerance at 24 weeks compared to baseline, as assessed by the the six minute hall walk (6MW) test. Note: An individual subject is considered a responder with >40-meter increase in distance walked at 24 weeks compared to their respective baseline distance.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Subjects who are 18 years of age or older

• Subjects who are either male or female

• Subjects who have a baseline ejection fraction of 35% or less by echocardiography.

• Subjects who have been treated for heart failure for at least 90 days (including treatment with a β-blocker for at least 90 days unless the patient is intolerant) and are in New York Heart Association functional Class III or IV at the time of enrollment.

• Subjects receiving appropriate, stable medical therapy during the 30 days prior to enrollment for treatment of heart failure, consisting of the appropriate doses of diuretics, ACE-inhibitor or angiotensin II receptor blocker and β-blocker. Stable is defined as no more than a 100% increase or 50% decrease in dose.

• Subjects who, in the opinion of the Principle Investigator (based on the current guidelines for clinical practice), have a clinical indication for an implanted cardiac defibrillator (ICD) and/or pacemaker, must have an existing device or agree to undergo implantation of such a device unless the patient refuses to undergo the implantation of such device for personal reasons.

• Subjects who are willing and able to return for all follow-up visits.

Exclusion Criteria:

• Subjects whose baseline VO2,max is <9 ml 02/min/kg.

• Subjects who have a potentially correctible cause of heart failure, such as valvular heart disease or congenital heart disease.

• Subjects who have clinically significant angina pectoris, consisting of angina during daily life (i.e., Canadian Cardiovascular Society Angina score of II or more), an episode of unstable angina within 30 days of enrollment, or angina and/or electrocardiography (ECG) changes during exercise testing performed during baseline evaluation.

• Subjects who have been hospitalized for heart failure which required the use of inotropic support within 30 days of enrollment.

• Subjects who have a clinically significant amount of ambient ectopy, defined as more than 8,900 premature ventricular complexes (PVCs) per 24 hours on baseline Holter monitoring.

• Subjects who have chronic atrial fibrillation or chronic atrial flutter or those cardioverted within 30 days of enrollment.

• Subjects whose exercise tolerance is limited by a condition other than heart failure (e.g., angina, chronic obstructive pulmonary disease [COPD], peripheral vascular disease, orthopedic or rheumatologic conditions) or who are unable to participate in a 6-minute walk or a cardiopulmonary stress test.

• Subjects who are scheduled for a coronary artery bypass graft (CABG) or a percutaneous transluminal coronary angioplasty (PTCA) procedure, or who have undergone a CABG procedure within 90 days or a PTCA procedure within 30 days of enrollment.

• Subjects who have a biventricular pacing system or who have an accepted indication for such a device.

• Subjects who have had a myocardial infarction within 90 days of enrollment.

• Subjects who have mechanical tricuspid or aortic valves.

• Subjects who have a prior heart transplant.

• Subjects who are participating in another experimental protocol.

• Subjects who are unable to provide informed consent.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Impulse Dynamics	Orangeburg	New York	United States	10962

Sponsors and Collaborators

• Impulse Dynamics

Investigators

• Study Director: Dan Burkhoff, M.D, Ph.D., Impulse Dynamics

Study Documents (Full-Text)

• Study Protocol, Statistical Analysis Plan, and Informed Consent Form - Aug 7, 2014

More Information

Publications

• Burkhoff D, Shemer I, Felzen B, Shimizu J, Mika Y, Dickstein M, Prutchi D, Darvish N, Ben-Haim SA. Electric currents applied during the refractory period can modulate cardiac contractility in vitro and in vivo. Heart Fail Rev. 2001 Jan;6(1):27-34. Review.
• Ellison K. Nonexcitatory stimulation: 2002: a pace odyssey. J Cardiovasc Electrophysiol. 2002 Jul;13(7):696-7.
• Marrouche NF, Pavia SV, Zhuang S, Kim YJ, Tabata T, Wallick D, Saad E, Abdul-Karim A, Schweikert R, Saliba W, Tchou P, Natale A. Nonexcitatory stimulus delivery improves left ventricular function in hearts with left bundle branch block. J Cardiovasc Electrophysiol. 2002 Jul;13(7):691-5.
• Mohri S, He KL, Dickstein M, Mika Y, Shimizu J, Shemer I, Yi GH, Wang J, Ben-Haim S, Burkhoff D. Cardiac contractility modulation by electric currents applied during the refractory period. Am J Physiol Heart Circ Physiol. 2002 May;282(5):H1642-7.
• Mohri S, Shimizu J, Mika Y, Shemer I, Wang J, Ben-Haim S, Burkhoff D. Electric currents applied during refractory period enhance contractility and systolic calcium in the ferret heart. Am J Physiol Heart Circ Physiol. 2003 Apr;284(4):H1119-23. Epub 2002 Nov 21.
• Morita H, Suzuki G, Haddad W, Mika Y, Tanhehco EJ, Sharov VG, Goldstein S, Ben-Haim S, Sabbah HN. Cardiac contractility modulation with nonexcitatory electric signals improves left ventricular function in dogs with chronic heart failure. J Card Fail. 2003 Feb;9(1):69-75.
• Pappone C, Rosanio S, Burkhoff D, Mika Y, Vicedomini G, Augello G, Shemer I, Prutchi D, Haddad W, Aviv R, Snir Y, Kronzon I, Alfieri O, Ben-Haim SA. Cardiac contractility modulation by electric currents applied during the refractory period in patients with heart failure secondary to ischemic or idiopathic dilated cardiomyopathy. Am J Cardiol. 2002 Dec 15;90(12):1307-13.
• Sabbah HN, Haddad W, Mika Y, Nass O, Aviv R, Sharov VG, Maltsev V, Felzen B, Undrovinas AI, Goldstein S, Darvish N, Ben-Haim SA. Cardiac contractility modulation with the impulse dynamics signal: studies in dogs with chronic heart failure. Heart Fail Rev. 2001 Jan;6(1):45-53. Review.

• Responsible Party: Impulse Dynamics
• ClinicalTrials.gov Identifier: NCT00112125
• Other Study ID Numbers: #IDPT 2003-07-C; FIX-HF-5
• First Posted: May 30, 2005
• Last Update Posted: Aug 6, 2020
• Last Verified: Jul 1, 2020

• Keywords provided by Impulse Dynamics: cardiac contractility modulation; heart failure; cardiopulmonary exercise test; chronic heart disease
• Additional relevant MeSH terms: Heart Failure

Study Results

Participant Flow

Arm/Group Title	Control Group (OMT)	Treatment (CCM + OMT)
Arm/Group Description	Optimal medical treatment (OMT). Subjects receiving appropriate, stable medical therapy during the 30 days prior to enrollment for treatment of heart failure, consisting of the appropriate doses of diuretics, ACE-inhibitor or angiotensin II receptor blocker and B-blocker.	Treatment group: Subjects receiving OMT and cardiac contractility modulation therapy with the Optimizer System.
Period Title: Overall Study
STARTED	213	215
COMPLETED	189	193
NOT COMPLETED	24	22

Baseline Characteristics

Arm/Group Title	Control Group (OMT)	Treatment (OMT + CCM)	Total
Arm/Group Description	Optimal medical treatment (OMT). Subjects receiving appropriate, stable medical therapy during the 30 days prior to enrollment for treatment of heart failure, consisting of the appropriate doses of diuretics, ACE-inhibitor or angiotensin II receptor blocker and B-blocker.	Treatment group: Subjects receiving OMT and cardiac contractility modulation therapy with the Optimizer System.	Total of all reporting groups
Overall Participants	213	215	428
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	58.6 (12.2)	58.1 (12.8)	58.35 (12.50)
Sex: Female, Male (Count of Participants)
Female	62 29.1%	57 26.5%	119 27.8%
Male	151 70.9%	158 73.5%	309 72.2%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 0.5%	2 0.9%	3 0.7%
Asian	4 1.9%	5 2.3%	9 2.1%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	45 21.1%	36 16.7%	81 18.9%
White	142 66.7%	154 71.6%	296 69.2%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	21 9.9%	18 8.4%	39 9.1%
Region of Enrollment (participants) [Number]
United States	213 100%	215 100%	428 100%
Peak VO2 (ml/kg/min) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [ml/kg/min]	14.71 (2.92)	14.74 (3.06)	14.725 (2.99)
6 Minute Hall Walk Distance (meters) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [meters]	324 (92.4)	326.4 (82.1)	325.2 (7.28)
NYHA Class III (Count of Participants)
Count of Participants [Participants]	183 85.9%	196 91.2%	379 88.6%
NYHA Class IV (Count of Participants)
Count of Participants [Participants]	29 13.6%	19 8.8%	48 11.2%
MLWHFQ score (Score on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Score on a scale]	57.4 (22.6)	60.5 (23)	58.95 (0.282)

Outcome Measures

1. Primary Outcome

Title	Efficacy Endpoint: Ventilatory Anerobic Threshold (VAT)
Description	Number of participants with improvement in exercise tolerance at 24 weeks compared to baseline, as quantified by VO2 at ventilatory anerobic threshold (VAT) measured on cardiopulmonary exercise stress testing (CPX), and evaluated by a blinded core lab. Note: An individual subject is considered a responder if VAT increases by ≥20% at 24 weeks compared to their respective baseline value.
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

Intention to treat (ITT) population

Arm/Group Title	Control Group (OMT)	Treatment (CCM + OMT)
Arm/Group Description	Optimal medical treatment (OMT). Subjects receiving appropriate, stable medical therapy during the 30 days prior to enrollment for treatment of heart failure, consisting of the appropriate doses of diuretics, ACE-inhibitor or angiotensin II receptor blocker and B-blocker.	Treatment group: Subjects receiving OMT and cardiac contractility modulation therapy with the Optimizer System.
Measure Participants	213	215
Count of Participants [Participants]	28 13.1%	38 17.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Control Group (OMT), Treatment (CCM + OMT)
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	The primary safety analysis was a test of the non-inferiority of CCM therapy compared to OMT with respect to the proportion of subjects experiencing death or hospitalization within 50 weeks using the Blackwelder non-inferiority test12 with a prespecified non-inferiority margin of 0.125.
Statistical Test of Hypothesis	p-Value	0.31
	Comments
	Method	Fisher Exact
	Comments

2. Primary Outcome

Title	Safety Endpoint: Composite All-cause Mortality and All-cause Hospitalizations
Description	The proportion of patients experiencing a composite event of all-cause mortality and all-cause hospitalizations evaluated at 50-weeks
Time Frame	50-weeks

Outcome Measure Data

Analysis Population Description

Intention-to-treat

Arm/Group Title	Control Group (OMT)	Treatment (CCM + OMT)
Arm/Group Description	Optimal medical treatment (OMT). Subjects receiving appropriate, stable medical therapy during the 30 days prior to enrollment for treatment of heart failure, consisting of the appropriate doses of diuretics, ACE-inhibitor or angiotensin II receptor blocker and B-blocker.	Treatment group: Subjects receiving OMT and cardiac contractility modulation therapy with the Optimizer System.
Measure Participants	213	215
Count of Participants [Participants]	103 48.4%	112 52.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Control Group (OMT), Treatment (CCM + OMT)
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	The noninferiority margin was selected to be 12.5% and α was set at .05, which resulted in a sample size of 198 subjects per group. A percentage of subjects (∼7%) were expected to be lost to followup, so that a total sample size of 428 subjects (214 per group) was selected.
Statistical Test of Hypothesis	p-Value	0.125
	Comments
	Method	Blackwelder
	Comments

3. Secondary Outcome

Title	Peak VO2
Description	Number of participants with improvement in peak VO2 measured on cardiopulmonary exercise stress testing (CPX), and evaluated by a blinded core lab. Note: An individual subject is considered a responder if peak VO2 increases by ≥20% at 24 weeks compared to their respective baseline value.
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

Completed cases

Arm/Group Title	Control Group (OMT)	Treatment (CCM + OMT)
Arm/Group Description	Optimal medical treatment (OMT). Subjects receiving appropriate, stable medical therapy during the 30 days prior to enrollment for treatment of heart failure, consisting of the appropriate doses of diuretics, ACE-inhibitor or angiotensin II receptor blocker and B-blocker.	Treatment group: Subjects receiving OMT and cardiac contractility modulation therapy with the Optimizer System.
Measure Participants	168	179
Count of Participants [Participants]	23 10.8%	31 14.4%

4. Secondary Outcome

Title	New York Heart Association (NYHA) Functional Classification
Description	Number of participants with improvement in heart failure symptoms as quantified by a blinded clinician using the New York Heart Association (NYHA) functional classification at 24 weeks compared to baseline. The NYHA Class ranges from I - IV, with a lower class indicating a better status. Note: An individual subject is considered a responder if the NYHA class decreases by ≥ 1 at 24 weeks compared to their respective baseline class.
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

Completed cases

Arm/Group Title	Control Group (OMT)	Treatment (CCM + OMT)
Arm/Group Description	Optimal medical treatment (OMT). Subjects receiving appropriate, stable medical therapy during the 30 days prior to enrollment for treatment of heart failure, consisting of the appropriate doses of diuretics, ACE-inhibitor or angiotensin II receptor blocker and B-blocker.	Treatment group: Subjects receiving OMT and cardiac contractility modulation therapy with the Optimizer System.
Measure Participants	183	191
Count of Participants [Participants]	63 29.6%	94 43.7%

5. Secondary Outcome

Title	Minnesota Living With Heart Failure (MLWHF) Questionnaire
Description	Number of subjects will improvement in quality of life at 24 weeks compared to baseline, as assessed by the Minnesota Living with Heart Failure (MLWHF) Questionnaire. The MLWHFQ score could range from 0 to 105, with higher scores indicating more significant impairment in health-related quality of life. Note: An individual subject is considered a responder if the MLWHFQ score decreases by ≥10 points at 24 weeks compared to their respective baseline score.
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

Completed cases

Arm/Group Title	Control Group (OMT)	Treatment (CCM + OMT)
Arm/Group Description	Optimal medical treatment (OMT). Subjects receiving appropriate, stable medical therapy during the 30 days prior to enrollment for treatment of heart failure, consisting of the appropriate doses of diuretics, ACE-inhibitor or angiotensin II receptor blocker and B-blocker.	Treatment group: Subjects receiving OMT and cardiac contractility modulation therapy with the Optimizer System.
Measure Participants	184	196
Count of Participants [Participants]	77 36.2%	110 51.2%

6. Secondary Outcome

Title	Six Minute Hall Walk (6MW) Test
Description	Number of subjects with improvement in exercise tolerance at 24 weeks compared to baseline, as assessed by the the six minute hall walk (6MW) test. Note: An individual subject is considered a responder with >40-meter increase in distance walked at 24 weeks compared to their respective baseline distance.
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

Completed cases

Arm/Group Title	Control Group (OMT)	Treatment (CCM + OMT)
Arm/Group Description	Optimal medical treatment (OMT). Subjects receiving appropriate, stable medical therapy during the 30 days prior to enrollment for treatment of heart failure, consisting of the appropriate doses of diuretics, ACE-inhibitor or angiotensin II receptor blocker and B-blocker.	Treatment group: Subjects receiving OMT and cardiac contractility modulation therapy with the Optimizer System.
Measure Participants	173	190
Count of Participants [Participants]	51 23.9%	65 30.2%

Adverse Events

Time Frame	50-weeks
Arm/Group Title	Control Group (OMT)		Treatment (CCM + OMT)
Arm/Group Description	Optimal medical treatment (OMT). Subjects receiving appropriate, stable medical therapy during the 30 days prior to enrollment for treatment of heart failure, consisting of the appropriate doses of diuretics, ACE-inhibitor or angiotensin II receptor blocker and B-blocker.		Treatment group: Subjects receiving OMT and cardiac contractility modulation therapy with the Optimizer System.
All Cause Mortality
	Control Group (OMT)		Treatment (CCM + OMT)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/212 (3.3%)		13/210 (6.2%)
Serious Adverse Events
	Control Group (OMT)		Treatment (CCM + OMT)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	115/212 (54.2%)		129/210 (61.4%)
Blood and lymphatic system disorders
Bleeding	8/212 (3.8%)	8	6/210 (2.9%)	8
OPTIMIZER pocket bleeding	0/212 (0%)	0	1/210 (0.5%)	1
Cardiac disorders
General Cardiopulmonary Event	46/212 (21.7%)	58	42/210 (20%)	60
Arrhythmia	25/212 (11.8%)	30	29/210 (13.8%)	40
ICD or Pacemaker System Malfunction	6/212 (2.8%)	7	11/210 (5.2%)	13
Worsening Heart Failure	50/212 (23.6%)	85	50/210 (23.8%)	72
General disorders
General Medical	54/212 (25.5%)	81	63/210 (30%)	98
Infections and infestations
Localized Infection	29/212 (13.7%)	36	27/210 (12.9%)	33
Sepsis	2/212 (0.9%)	2	10/210 (4.8%)	11
OPTIMIZER pocket infection	0/212 (0%)	0	2/210 (1%)	2
Nervous system disorders
Neurologic Dysfunction	12/212 (5.7%)	14	3/210 (1.4%)	3
Surgical and medical procedures
OPTIMIZER lead fracture	0/212 (0%)	0	3/210 (1.4%)	3
OPTIMIZER RV lead dislodgement	0/212 (0%)	0	6/210 (2.9%)	6
IPG problem/change	0/212 (0%)	0	1/210 (0.5%)	2
OPTIMIZER RA lead dislodgement	0/212 (0%)	0	5/210 (2.4%)	6
OPTIMIZER pocket dehiscence/erosion	0/212 (0%)	0	3/210 (1.4%)	3
OPTIMIZER pocket stimulation	0/212 (0%)	0	2/210 (1%)	2
Lead perforation	0/212 (0%)	0	2/210 (1%)	2
Sensation due to CCM	0/212 (0%)	0	2/210 (1%)	2
Extracardiac stimulation	0/212 (0%)	0	1/210 (0.5%)	1
Vascular disorders
Thromboembolism	5/212 (2.4%)	5	3/210 (1.4%)	3
Other (Not Including Serious) Adverse Events
	Control Group (OMT)		Treatment (CCM + OMT)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	135/212 (63.7%)		152/210 (72.4%)
Cardiac disorders
General Cardiopulmonary Event	19/212 (9%)	21	41/210 (19.5%)	55
Arrhythmias	13/212 (6.1%)	16	26/210 (12.4%)	29
Worsening Heart Failure	29/212 (13.7%)	35	32/210 (15.2%)	35
General disorders
General Medical	86/212 (40.6%)	167	105/210 (50%)	193
Infections and infestations
Localized Infection	41/212 (19.3%)	50	51/210 (24.3%)	63

Limitations/Caveats

The primary endpoint was not validated for use in HF trials (VAT, responder analysis, responder = 20% increase). VAT was missing or indeterminant in 30% of subjects despite use of 2 blinded core labs. ITT analysis required 10 levels of imputation.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.