Heart Failure, Congestive
Conditions
Keywords
Acute decompensated heart failure, heart failure, MRI, trpV4 channel inhibitors, pulmonary oedema
Brief summary
Transient receptor potential vanilloid 4 (TRPV4) channel blockade may be promising in the treatment of pulmonary oedema and dyspnoea in heart failure (HF) and acute decompensated heart failure (ADHF) patients by re-establishing the alveolar septal barrier. Dynamic contrast enhanced (DCE) Magnetic Resonance Imaging (MRI) is an established technique for assessing changes in vascular permeability and interstitial water volume. The aim of this study is to establish the potential utility of DCE-MRI as a novel endpoint for dose ranging and proof of mechanism studies of TRPV4 blockers. The DCE-MRI markers of vascular permeability and pulmonary oedema will be measured in subjects with HF (group 2) and healthy volunteers (HV) (group 1) at rest to determine if there is a difference between the two populations. Apart from this, exercise induced changes relative to rest in interstitial volume and exchange rate will be evaluated in both HV and subjects with HF. Additionally, the capability of DCE-MRI to detect changes in interstitial lung fluid in patients with acute decompensated heart failure (ADHF) (group 3) will be investigated. DCE-MRI markers of pulmonary oedema will be assessed when patients are initially hospitalized with ADHF and subsequently after receiving standard of care treatment to determine whether differences can be detected by this methodology.This study will enrol a sufficient number of subjects to have at least 24 subjects in Group 1 and 2 (group 1:12 HV and group 2: 12 subjects with HF) and atleast 5 subjects in Group 3. For each subject, the MRI data must be of sufficient quality to enable DCE-MRI modelling from 2 Sessions. For group 1 and 2, the subjects will have screening visit and 3 MRI sessions. For the first scanning session, subjects will undergo the baseline procedure. The second imaging session will occur approximately one week later to measure within subject variability. A third imaging session (which will be conducted in 2 visits) will incorporate a bicycle exercise challenge prior to the MRI scan, and this third scan will be performed approximately one to three days after the second imaging session. For group 3: Screening will occur during hospitalization for eligibility. Session 1of MRI will be conducted while the subject is still hospitalized. Session 2 will be conducted within 4 weeks of the first scan, when the signs of pulmonary oedema are considered to be resolved. If a subject's pulmonary oedema has not resolved at Session 2, then the subject will be not be scanned by MRI at Session 2 and will be brought back for Session 3 up to 4 weeks after Session 2 for their second MRI.
Interventions
PROCEDUREDCE-MRI scans
Subjects will be placed supine in the scanner and will be prepared for intravenous contrast agent administration. The contrast agent is administered using a power injector before imaging.
OTHERGadobutrol
Gadobutrol at a dose less than or equal to 0.1 millimoles per kilogram (mmol/kg) will be given intravenously as a bolus using a power injector.
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Male or females over 18 years of age at the time of signing the informed consent. * Body weight \>=50 kilogram (kg) and Body Mass Index (BMI) within the range 18.0-40.0 kilogram/square meter (kg/m\^2) (inclusive). * Able to understand and comply with protocol requirements, instructions and protocol stated restrictions and is willing to take part in the imaging sessions. * Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form. Inclusion Criteria for Heart Failure Group (group 2) - Established diagnosis of mild to moderate heart failure of any aetiology with symptoms defined as corresponding to the New York Heart Association (NYHA) class II or III. Inclusion Criteria for Healthy Volunteer Group (group 1) \- Healthy as determined by a responsible and experienced physician, based on a medical evaluation including medical history, brief physical examination, clinical laboratory tests, and Electrocardiogram (ECG). Inclusion Criteria for Subjects with ADHF (Group 3) * Male subjects OR female subjects of non reproductive potential as defined as pre-menopausal females with a documented tubal ligation or hysterectomy, or post-menopausal defined as 12 months of spontaneous amenorrhea \[in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) \> 40 million international units (MIU)/millilitre (mL) and oestradiol \< 40picogram (pg)/mL (\< 140 pmol/L) is confirmatory. * 50 years of age or over at the time of signing the informed consent * Hospitalized for the management of acute decompensated HF * Presence of dyspnoea at rest or with minimal activity * Presence of at least one of the following signs: Tachypnea with respiratory rate \>=20 breaths/min or Rales or crackles audible on auscultation * Chest x-ray with evidence of pulmonary congestion/oedema performed approximately within the last 48 hours (if not available - an additional research CXR may be requested) * Have received at least one treatment with an intravenous diuretic prior to the first MRI scan * Body weight \>= 50kg and BMI within the range 18-40 kg/m\^2 (inclusive) * Able to understand and comply with protocol requirements, instructions and protocol-stated restrictions and is willing to take part in the imaging sessions * Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Exchange Rate (Ktrans) in ADHF Participants | Up to Week 8 | Exchange rate (Ktrans) was measured by DCE-MRI. Three participants underwent 3 DCE-MRI scans. The data has been presented for individual participant in each session. The data presented below is only for total lung. |
| Exchange Rate (Ktrans) in Heart Failure Participants and Healthy Volunteers Before and Following Exercise | Day 11 | Exchange rate (Ktrans) was measured by DCE-MRI. Ktrans for total lung, left lung, right lung, left lung apical, left lung basal, right lung apical, right lung basal before and following exercise has been presented. |
| Change in Interstitial Volume (ve) in ADHF Participants | Up to Week 8 | Interstitial volume (ve) was measured by DCE-MRI. Three participants underwent 3 DCE-MRI scans. The data has been presented for individual participant in each session. The data presented below is only for total lung. |
| Interstitial Volume (ve) in Heart Failure Participants and Healthy Volunteers at Baseline | Day 1 | Interstitial volume (ve) was measured by DCE-MRI. ve for total lung, left lung, right lung, left lung apical, left lung basal, right lung apical, right lung basal has been presented. Session 1 values were considered as Baseline values. |
| Exchange Rate (Ktrans) in Heart Failure Participants and Healthy Volunteers at Baseline | Day 1 | Exchange rate (Ktrans) was measured by DCE-MRI. Ktrans for total lung, left lung, right lung, left lung apical, left lung basal, right lung apical, right lung basal has been presented. Session 1 values were considered as Baseline values. |
| Interstitial Volume (ve) in Heart Failure Participants and Healthy Volunteers Before and Following Exercise | Day 11 | Interstitial volume (ve) was measured by DCE-MRI. ve for total lung, left lung, right lung, left lung apical, left lung basal, right lung apical, right lung basal before and following exercise has been presented. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Assessment of Intra-subject Variability in Ktrans Between Session 1 and Session 2 of DCE-MRI | Day 1 (Session 1) and Day 9 (Session 2) | Coefficient of variation (percentage) of intra-subject variability in Ktrans between Session 1 and Session 2 for total lung has been presented. |
| Assessment of Intra-subject Variability in Ve Between Session 1 and Session 2 of DCE-MRI | Day 1 (Session 1) and Day 9 (Session 2) | Coefficient of variation (percentage) of intra-subject variability in Ve between Session 1 and Session 2 for total lung has been presented. |
Countries
United Kingdom
Participant flow
Recruitment details
This study included healthy volunteers (HV, group 1), participants (par) with heart failure (HF, group 2) and participants with acute decompensated heart failure (ADHF, group 3) who were hospitalized with evidence of pulmonary edema and received standard of care treatment.
Pre-assignment details
Dynamic Contrast Enhanced-Magnetic Resonance Imaging (DCE-MRI) markers were used to measure vascular permeability and pulmonary edema in HV and par. with HF. Forty one par. were enrolled and 36 entered the study. Three par. did not continue due to habitus and 2 par. did not participate as they required clinical investigations.
Participants by arm
| Arm | Count |
|---|---|
| Healthy Volunteers Healthy volunteers were placed in supine position under the scanner and intravenous contrast agent was administered. Contrast agent was administered as a bolus using a power injector during the dynamic series. MRI scanning was conducted by experienced radiographers and radiologists in the nominated scanning sites, using a 1.5 Tesla (T) system. | 21 |
| Heart Failure Participants Heart failure participants were placed in supine position under the scanner and intravenous contrast agent was administered. Contrast agent was administered as a bolus using a power injector during the dynamic series. MRI scanning was conducted by experienced radiographers and radiologists in the nominated scanning sites, using a 1.5 Tesla (T) system. | 12 |
| Acute Decompensated Heart Failure Participants Acute Decompensated Heart Failure participants following hospitalization due to pulmonary oedema was placed in supine position under the scanner and intravenous contrast agent was administered. Contrast agent was administered as a bolus using a power injector during the dynamic series. MRI scanning was conducted by experienced radiographers and radiologists in the nominated scanning sites, using a 1.5 Tesla (T) system. | 3 |
| Total | 36 |
Baseline characteristics
| Characteristic | Healthy Volunteers | Heart Failure Participants | Acute Decompensated Heart Failure Participants | Total |
|---|---|---|---|---|
| Age, Continuous | 53.8 Years STANDARD_DEVIATION 18.66 | 67.8 Years STANDARD_DEVIATION 13.42 | 79.3 Years STANDARD_DEVIATION 4.93 | 66.9 Years STANDARD_DEVIATION 6.9 |
| Race/Ethnicity, Customized African American/African Heritage | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 21 Participants | 11 Participants | 3 Participants | 35 Participants |
| Sex: Female, Male Female | 2 Participants | 2 Participants | 1 Participants | 5 Participants |
| Sex: Female, Male Male | 19 Participants | 10 Participants | 2 Participants | 31 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 17 | 0 / 12 | 0 / 3 |
| other Total, other adverse events | 0 / 17 | 0 / 12 | 0 / 3 |
| serious Total, serious adverse events | 0 / 17 | 0 / 12 | 0 / 3 |
Outcome results
Primary
Change in Exchange Rate (Ktrans) in ADHF Participants
Exchange rate (Ktrans) was measured by DCE-MRI. Three participants underwent 3 DCE-MRI scans. The data has been presented for individual participant in each session. The data presented below is only for total lung.
Time frame: Up to Week 8
Population: The Safety Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Healthy Volunteers | Change in Exchange Rate (Ktrans) in ADHF Participants | Par.1; Session 1 | 0.4524 Liter/minute |
| Healthy Volunteers | Change in Exchange Rate (Ktrans) in ADHF Participants | Par.1; Session 2 | 0.5306 Liter/minute |
| Healthy Volunteers | Change in Exchange Rate (Ktrans) in ADHF Participants | Par. 2; Session 1 | 0.3018 Liter/minute |
| Healthy Volunteers | Change in Exchange Rate (Ktrans) in ADHF Participants | Par. 3; Session 2 | 0.4304 Liter/minute |
| Healthy Volunteers | Change in Exchange Rate (Ktrans) in ADHF Participants | Par. 3 Session 3 | 0.4264 Liter/minute |
| Healthy Volunteers | Change in Exchange Rate (Ktrans) in ADHF Participants | Par. 2; Session 2 | 0.1952 Liter/minute |
| Healthy Volunteers | Change in Exchange Rate (Ktrans) in ADHF Participants | Par. 3; Session 1 | 0.1602 Liter/minute |
Primary
Change in Interstitial Volume (ve) in ADHF Participants
Interstitial volume (ve) was measured by DCE-MRI. Three participants underwent 3 DCE-MRI scans. The data has been presented for individual participant in each session. The data presented below is only for total lung.
Time frame: Up to Week 8
Population: The safety population will include all enrolled participants who have initiated at least one session of DCE-MRI or Lung Ultrasound Scan
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Healthy Volunteers | Change in Interstitial Volume (ve) in ADHF Participants | Par.1; Session 1 | 0.794 Liter |
| Healthy Volunteers | Change in Interstitial Volume (ve) in ADHF Participants | Par.1; Session 2 | 0.9577 Liter |
| Healthy Volunteers | Change in Interstitial Volume (ve) in ADHF Participants | Par. 2; Session 1 | 0.5086 Liter |
| Healthy Volunteers | Change in Interstitial Volume (ve) in ADHF Participants | Par. 2; Session 2 | 0.4018 Liter |
| Healthy Volunteers | Change in Interstitial Volume (ve) in ADHF Participants | Par. 3; Session 1 | 0.354 Liter |
| Healthy Volunteers | Change in Interstitial Volume (ve) in ADHF Participants | Par. 3; Session 2 | 0.6356 Liter |
| Healthy Volunteers | Change in Interstitial Volume (ve) in ADHF Participants | Par. 3 Session 3 | 0.6083 Liter |
Primary
Exchange Rate (Ktrans) in Heart Failure Participants and Healthy Volunteers at Baseline
Exchange rate (Ktrans) was measured by DCE-MRI. Ktrans for total lung, left lung, right lung, left lung apical, left lung basal, right lung apical, right lung basal has been presented. Session 1 values were considered as Baseline values.
Time frame: Day 1
Population: The Evaluable Population
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Healthy Volunteers | Exchange Rate (Ktrans) in Heart Failure Participants and Healthy Volunteers at Baseline | Total lung | 0.2216 Liter/minute | Standard Error 0.0298 |
| Healthy Volunteers | Exchange Rate (Ktrans) in Heart Failure Participants and Healthy Volunteers at Baseline | Left lung | 0.2309 Liter/minute | Standard Error 0.0256 |
| Healthy Volunteers | Exchange Rate (Ktrans) in Heart Failure Participants and Healthy Volunteers at Baseline | Right lung | 0.2216 Liter/minute | Standard Error 0.0338 |
| Healthy Volunteers | Exchange Rate (Ktrans) in Heart Failure Participants and Healthy Volunteers at Baseline | Left lung apical | 0.2166 Liter/minute | Standard Error 0.0265 |
| Healthy Volunteers | Exchange Rate (Ktrans) in Heart Failure Participants and Healthy Volunteers at Baseline | Left lung basal | 0.2621 Liter/minute | Standard Error 0.027 |
| Healthy Volunteers | Exchange Rate (Ktrans) in Heart Failure Participants and Healthy Volunteers at Baseline | Right lung apical | 0.2166 Liter/minute | Standard Error 0.0355 |
| Healthy Volunteers | Exchange Rate (Ktrans) in Heart Failure Participants and Healthy Volunteers at Baseline | Right lung basal | 0.2313 Liter/minute | Standard Error 0.0329 |
| Heart Failure Participants | Exchange Rate (Ktrans) in Heart Failure Participants and Healthy Volunteers at Baseline | Total lung | 0.2353 Liter/minute | Standard Error 0.0273 |
| Heart Failure Participants | Exchange Rate (Ktrans) in Heart Failure Participants and Healthy Volunteers at Baseline | Left lung basal | 0.2225 Liter/minute | Standard Error 0.0249 |
| Heart Failure Participants | Exchange Rate (Ktrans) in Heart Failure Participants and Healthy Volunteers at Baseline | Left lung | 0.2173 Liter/minute | Standard Error 0.0236 |
| Heart Failure Participants | Exchange Rate (Ktrans) in Heart Failure Participants and Healthy Volunteers at Baseline | Right lung basal | 0.2431 Liter/minute | Standard Error 0.0301 |
| Heart Failure Participants | Exchange Rate (Ktrans) in Heart Failure Participants and Healthy Volunteers at Baseline | Right lung | 0.2474 Liter/minute | Standard Error 0.0309 |
| Heart Failure Participants | Exchange Rate (Ktrans) in Heart Failure Participants and Healthy Volunteers at Baseline | Right lung apical | 0.2528 Liter/minute | Standard Error 0.0326 |
| Heart Failure Participants | Exchange Rate (Ktrans) in Heart Failure Participants and Healthy Volunteers at Baseline | Left lung apical | 0.2161 Liter/minute | Standard Error 0.0244 |
p-value: 0.793695% CI: [-0.1036, 0.08]ANOVA
p-value: 0.738195% CI: [-0.0968, 0.0695]ANOVA
p-value: 0.699295% CI: [-0.058, 0.0852]ANOVA
p-value: 0.577895% CI: [-0.1201, 0.0684]ANOVA
p-value: 0.989995% CI: [-0.0738, 0.0747]ANOVA
p-value: 0.291295% CI: [-0.036, 0.1153]ANOVA
p-value: 0.459295% CI: [-0.1355, 0.0631]ANOVA
Primary
Exchange Rate (Ktrans) in Heart Failure Participants and Healthy Volunteers Before and Following Exercise
Exchange rate (Ktrans) was measured by DCE-MRI. Ktrans for total lung, left lung, right lung, left lung apical, left lung basal, right lung apical, right lung basal before and following exercise has been presented.
Time frame: Day 11
Population: The Evaluable Population
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Healthy Volunteers | Exchange Rate (Ktrans) in Heart Failure Participants and Healthy Volunteers Before and Following Exercise | Pre-exercise; Total lung | 0.2044 Liter/minute | Standard Error 0.0281 |
| Healthy Volunteers | Exchange Rate (Ktrans) in Heart Failure Participants and Healthy Volunteers Before and Following Exercise | Post-exercise; Total lung | 0.1841 Liter/minute | Standard Error 0.0221 |
| Healthy Volunteers | Exchange Rate (Ktrans) in Heart Failure Participants and Healthy Volunteers Before and Following Exercise | Pre-exercise; Left lung | 0.2102 Liter/minute | Standard Error 0.0285 |
| Healthy Volunteers | Exchange Rate (Ktrans) in Heart Failure Participants and Healthy Volunteers Before and Following Exercise | Post-exercise; Left lung | 0.1785 Liter/minute | Standard Error 0.02 |
| Healthy Volunteers | Exchange Rate (Ktrans) in Heart Failure Participants and Healthy Volunteers Before and Following Exercise | Pre-exercise; Right lung | 0.2034 Liter/minute | Standard Error 0.0299 |
| Healthy Volunteers | Exchange Rate (Ktrans) in Heart Failure Participants and Healthy Volunteers Before and Following Exercise | Post-exercise; Right lung | 0.1926 Liter/minute | Standard Error 0.0269 |
| Healthy Volunteers | Exchange Rate (Ktrans) in Heart Failure Participants and Healthy Volunteers Before and Following Exercise | Pre-exercise; Left lung apical | 0.1856 Liter/minute | Standard Error 0.0293 |
| Healthy Volunteers | Exchange Rate (Ktrans) in Heart Failure Participants and Healthy Volunteers Before and Following Exercise | Post-exercise; Left lung apical | 0.1621 Liter/minute | Standard Error 0.0199 |
| Healthy Volunteers | Exchange Rate (Ktrans) in Heart Failure Participants and Healthy Volunteers Before and Following Exercise | Pre-exercise; Left lung basal | 0.2552 Liter/minute | Standard Error 0.0296 |
| Healthy Volunteers | Exchange Rate (Ktrans) in Heart Failure Participants and Healthy Volunteers Before and Following Exercise | Post-exercise; Left lung basal | 0.2060 Liter/minute | Standard Error 0.0227 |
| Healthy Volunteers | Exchange Rate (Ktrans) in Heart Failure Participants and Healthy Volunteers Before and Following Exercise | Post-exercise; Right lung apical | 0.1892 Liter/minute | Standard Error 0.0267 |
| Healthy Volunteers | Exchange Rate (Ktrans) in Heart Failure Participants and Healthy Volunteers Before and Following Exercise | Pre-exercise; Right lung basal | 0.2181 Liter/minute | Standard Error 0.0319 |
| Healthy Volunteers | Exchange Rate (Ktrans) in Heart Failure Participants and Healthy Volunteers Before and Following Exercise | Post-exercise; Right lung basal | 0.2052 Liter/minute | Standard Error 0.0284 |
| Healthy Volunteers | Exchange Rate (Ktrans) in Heart Failure Participants and Healthy Volunteers Before and Following Exercise | Pre-exercise; Right lung apical | 0.1934 Liter/minute | Standard Error 0.0281 |
| Heart Failure Participants | Exchange Rate (Ktrans) in Heart Failure Participants and Healthy Volunteers Before and Following Exercise | Post-exercise; Right lung apical | 0.2141 Liter/minute | Standard Error 0.0224 |
| Heart Failure Participants | Exchange Rate (Ktrans) in Heart Failure Participants and Healthy Volunteers Before and Following Exercise | Pre-exercise; Total lung | 0.2567 Liter/minute | Standard Error 0.0247 |
| Heart Failure Participants | Exchange Rate (Ktrans) in Heart Failure Participants and Healthy Volunteers Before and Following Exercise | Post-exercise; Left lung apical | 0.1780 Liter/minute | Standard Error 0.0167 |
| Heart Failure Participants | Exchange Rate (Ktrans) in Heart Failure Participants and Healthy Volunteers Before and Following Exercise | Post-exercise; Total lung | 0.2108 Liter/minute | Standard Error 0.019 |
| Heart Failure Participants | Exchange Rate (Ktrans) in Heart Failure Participants and Healthy Volunteers Before and Following Exercise | Post-exercise; Right lung basal | 0.2081 Liter/minute | Standard Error 0.0238 |
| Heart Failure Participants | Exchange Rate (Ktrans) in Heart Failure Participants and Healthy Volunteers Before and Following Exercise | Pre-exercise; Left lung | 0.2525 Liter/minute | Standard Error 0.0245 |
| Heart Failure Participants | Exchange Rate (Ktrans) in Heart Failure Participants and Healthy Volunteers Before and Following Exercise | Pre-exercise; Left lung basal | 0.2630 Liter/minute | Standard Error 0.0254 |
| Heart Failure Participants | Exchange Rate (Ktrans) in Heart Failure Participants and Healthy Volunteers Before and Following Exercise | Post-exercise; Left lung | 0.1986 Liter/minute | Standard Error 0.0172 |
| Heart Failure Participants | Exchange Rate (Ktrans) in Heart Failure Participants and Healthy Volunteers Before and Following Exercise | Pre-exercise; Right lung basal | 0.2593 Liter/minute | Standard Error 0.0281 |
| Heart Failure Participants | Exchange Rate (Ktrans) in Heart Failure Participants and Healthy Volunteers Before and Following Exercise | Pre-exercise; Right lung | 0.2550 Liter/minute | Standard Error 0.0263 |
| Heart Failure Participants | Exchange Rate (Ktrans) in Heart Failure Participants and Healthy Volunteers Before and Following Exercise | Post-exercise; Left lung basal | 0.2185 Liter/minute | Standard Error 0.0196 |
| Heart Failure Participants | Exchange Rate (Ktrans) in Heart Failure Participants and Healthy Volunteers Before and Following Exercise | Post-exercise; Right lung | 0.2114 Liter/minute | Standard Error 0.0226 |
| Heart Failure Participants | Exchange Rate (Ktrans) in Heart Failure Participants and Healthy Volunteers Before and Following Exercise | Pre-exercise; Right lung apical | 0.2440 Liter/minute | Standard Error 0.0243 |
| Heart Failure Participants | Exchange Rate (Ktrans) in Heart Failure Participants and Healthy Volunteers Before and Following Exercise | Pre-exercise; Left lung apical | 0.2459 Liter/minute | Standard Error 0.0253 |
p-value: 0.17395% CI: [-0.1292, 0.0244]ANOVA
p-value: 0.270495% CI: [-0.1196, 0.0349]ANOVA
p-value: 0.207295% CI: [-0.1334, 0.0303]ANOVA
p-value: 0.130795% CI: [-0.1398, 0.0191]ANOVA
p-value: 0.842795% CI: [-0.0879, 0.0722]ANOVA
p-value: 0.184895% CI: [-0.1269, 0.0257]ANOVA
p-value: 0.340895% CI: [-0.1286, 0.0461]ANOVA
p-value: 0.368295% CI: [-0.0866, 0.0332]ANOVA
p-value: 0.453195% CI: [-0.0744, 0.0342]ANOVA
p-value: 0.59795% CI: [-0.0909, 0.0533]ANOVA
p-value: 0.547295% CI: [-0.0693, 0.0375]ANOVA
p-value: 0.679395% CI: [-0.0742, 0.0491]ANOVA
p-value: 0.480695% CI: [-0.0964, 0.0466]ANOVA
p-value: 0.937995% CI: [-0.0789, 0.0731]ANOVA
Primary
Interstitial Volume (ve) in Heart Failure Participants and Healthy Volunteers at Baseline
Interstitial volume (ve) was measured by DCE-MRI. ve for total lung, left lung, right lung, left lung apical, left lung basal, right lung apical, right lung basal has been presented. Session 1 values were considered as Baseline values.
Time frame: Day 1
Population: The Evaluable Population will include participants in safety population who are 40 years and older .The safety Population includes all enrolled participants who have initiated Session 1 DCE-MRI scan
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Healthy Volunteers | Interstitial Volume (ve) in Heart Failure Participants and Healthy Volunteers at Baseline | Right lung | 0.4960 Liter | Standard Error 0.0417 |
| Healthy Volunteers | Interstitial Volume (ve) in Heart Failure Participants and Healthy Volunteers at Baseline | Left lung basal | 0.5349 Liter | Standard Error 0.0397 |
| Healthy Volunteers | Interstitial Volume (ve) in Heart Failure Participants and Healthy Volunteers at Baseline | Left lung | 0.5078 Liter | Standard Error 0.0349 |
| Healthy Volunteers | Interstitial Volume (ve) in Heart Failure Participants and Healthy Volunteers at Baseline | Right lung apical | 0.4865 Liter | Standard Error 0.0392 |
| Healthy Volunteers | Interstitial Volume (ve) in Heart Failure Participants and Healthy Volunteers at Baseline | Left lung apical | 0.4952 Liter | Standard Error 0.0339 |
| Healthy Volunteers | Interstitial Volume (ve) in Heart Failure Participants and Healthy Volunteers at Baseline | Right lung basal | 0.5045 Liter | Standard Error 0.0444 |
| Healthy Volunteers | Interstitial Volume (ve) in Heart Failure Participants and Healthy Volunteers at Baseline | Total lung | 0.4946 Liter | Standard Error 0.0362 |
| Heart Failure Participants | Interstitial Volume (ve) in Heart Failure Participants and Healthy Volunteers at Baseline | Right lung basal | 0.3297 Liter | Standard Error 0.039 |
| Heart Failure Participants | Interstitial Volume (ve) in Heart Failure Participants and Healthy Volunteers at Baseline | Total lung | 0.3346 Liter | Standard Error 0.0325 |
| Heart Failure Participants | Interstitial Volume (ve) in Heart Failure Participants and Healthy Volunteers at Baseline | Left lung | 0.3253 Liter | Standard Error 0.0317 |
| Heart Failure Participants | Interstitial Volume (ve) in Heart Failure Participants and Healthy Volunteers at Baseline | Right lung | 0.3395 Liter | Standard Error 0.0371 |
| Heart Failure Participants | Interstitial Volume (ve) in Heart Failure Participants and Healthy Volunteers at Baseline | Left lung apical | 0.3188 Liter | Standard Error 0.0306 |
| Heart Failure Participants | Interstitial Volume (ve) in Heart Failure Participants and Healthy Volunteers at Baseline | Left lung basal | 0.3350 Liter | Standard Error 0.0362 |
| Heart Failure Participants | Interstitial Volume (ve) in Heart Failure Participants and Healthy Volunteers at Baseline | Right lung apical | 0.3506 Liter | Standard Error 0.0352 |
p-value: 0.002995% CI: [0.06, 0.26]ANOVA
p-value: 0.000795% CI: [0.0855, 0.2795]ANOVA
p-value: 0.009395% CI: [0.0419, 0.2711]ANOVA
p-value: 0.000795% CI: [0.0823, 0.2704]ANOVA
p-value: 0.00195% CI: [0.0894, 0.3103]ANOVA
p-value: 0.015995% CI: [0.0276, 0.2443]ANOVA
p-value: 0.006495% CI: [0.0535, 0.2961]ANOVA
Primary
Interstitial Volume (ve) in Heart Failure Participants and Healthy Volunteers Before and Following Exercise
Interstitial volume (ve) was measured by DCE-MRI. ve for total lung, left lung, right lung, left lung apical, left lung basal, right lung apical, right lung basal before and following exercise has been presented.
Time frame: Day 11
Population: The Evaluable Population
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Healthy Volunteers | Interstitial Volume (ve) in Heart Failure Participants and Healthy Volunteers Before and Following Exercise | Pre-exercise; Total lung | 0.4353 Liter | Standard Error 0.0335 |
| Healthy Volunteers | Interstitial Volume (ve) in Heart Failure Participants and Healthy Volunteers Before and Following Exercise | Post-exercise; Total lung | 0.4568 Liter | Standard Error 0.0307 |
| Healthy Volunteers | Interstitial Volume (ve) in Heart Failure Participants and Healthy Volunteers Before and Following Exercise | Pre-exercise; Left lung | 0.4487 Liter | Standard Error 0.0311 |
| Healthy Volunteers | Interstitial Volume (ve) in Heart Failure Participants and Healthy Volunteers Before and Following Exercise | Post-exercise; Left lung | 0.4832 Liter | Standard Error 0.0266 |
| Healthy Volunteers | Interstitial Volume (ve) in Heart Failure Participants and Healthy Volunteers Before and Following Exercise | Pre-exercise; Right lung | 0.4361 Liter | Standard Error 0.0357 |
| Healthy Volunteers | Interstitial Volume (ve) in Heart Failure Participants and Healthy Volunteers Before and Following Exercise | Post-exercise; Right lung | 0.4534 Liter | Standard Error 0.0355 |
| Healthy Volunteers | Interstitial Volume (ve) in Heart Failure Participants and Healthy Volunteers Before and Following Exercise | Pre-exercise; Left lung apical | 0.4272 Liter | Standard Error 0.0335 |
| Healthy Volunteers | Interstitial Volume (ve) in Heart Failure Participants and Healthy Volunteers Before and Following Exercise | Post-exercise; Left lung apical | 0.4449 Liter | Standard Error 0.0257 |
| Healthy Volunteers | Interstitial Volume (ve) in Heart Failure Participants and Healthy Volunteers Before and Following Exercise | Pre-exercise; Left lung basal | 0.4890 Liter | Standard Error 0.0318 |
| Healthy Volunteers | Interstitial Volume (ve) in Heart Failure Participants and Healthy Volunteers Before and Following Exercise | Post-exercise; Left lung basal | 0.5310 Liter | Standard Error 0.0323 |
| Healthy Volunteers | Interstitial Volume (ve) in Heart Failure Participants and Healthy Volunteers Before and Following Exercise | Pre-exercise; Right lung apical | 0.4343 Liter | Standard Error 0.0378 |
| Healthy Volunteers | Interstitial Volume (ve) in Heart Failure Participants and Healthy Volunteers Before and Following Exercise | Pre-exercise; Right lung basal | 0.4400 Liter | Standard Error 0.0347 |
| Healthy Volunteers | Interstitial Volume (ve) in Heart Failure Participants and Healthy Volunteers Before and Following Exercise | Post-exercise; Right lung basal | 0.4591 Liter | Standard Error 0.0367 |
| Healthy Volunteers | Interstitial Volume (ve) in Heart Failure Participants and Healthy Volunteers Before and Following Exercise | Post-exercise; Right lung apical | 0.4504 Liter | Standard Error 0.0358 |
| Heart Failure Participants | Interstitial Volume (ve) in Heart Failure Participants and Healthy Volunteers Before and Following Exercise | Pre-exercise; Right lung apical | 0.3387 Liter | Standard Error 0.0324 |
| Heart Failure Participants | Interstitial Volume (ve) in Heart Failure Participants and Healthy Volunteers Before and Following Exercise | Pre-exercise; Total lung | 0.3205 Liter | Standard Error 0.0292 |
| Heart Failure Participants | Interstitial Volume (ve) in Heart Failure Participants and Healthy Volunteers Before and Following Exercise | Post-exercise; Left lung apical | 0.2986 Liter | Standard Error 0.0216 |
| Heart Failure Participants | Interstitial Volume (ve) in Heart Failure Participants and Healthy Volunteers Before and Following Exercise | Post-exercise; Total lung | 0.3140 Liter | Standard Error 0.0263 |
| Heart Failure Participants | Interstitial Volume (ve) in Heart Failure Participants and Healthy Volunteers Before and Following Exercise | Post-exercise; Right lung basal | 0.3133 Liter | Standard Error 0.0308 |
| Heart Failure Participants | Interstitial Volume (ve) in Heart Failure Participants and Healthy Volunteers Before and Following Exercise | Pre-exercise; Left lung | 0.3121 Liter | Standard Error 0.0267 |
| Heart Failure Participants | Interstitial Volume (ve) in Heart Failure Participants and Healthy Volunteers Before and Following Exercise | Pre-exercise; Left lung basal | 0.3114 Liter | Standard Error 0.0272 |
| Heart Failure Participants | Interstitial Volume (ve) in Heart Failure Participants and Healthy Volunteers Before and Following Exercise | Post-exercise; Left lung | 0.3055 Liter | Standard Error 0.0228 |
| Heart Failure Participants | Interstitial Volume (ve) in Heart Failure Participants and Healthy Volunteers Before and Following Exercise | Pre-exercise; Right lung basal | 0.3206 Liter | Standard Error 0.0301 |
| Heart Failure Participants | Interstitial Volume (ve) in Heart Failure Participants and Healthy Volunteers Before and Following Exercise | Pre-exercise; Right lung | 0.3294 Liter | Standard Error 0.0311 |
| Heart Failure Participants | Interstitial Volume (ve) in Heart Failure Participants and Healthy Volunteers Before and Following Exercise | Post-exercise; Left lung basal | 0.3173 Liter | Standard Error 0.0276 |
| Heart Failure Participants | Interstitial Volume (ve) in Heart Failure Participants and Healthy Volunteers Before and Following Exercise | Post-exercise; Right lung | 0.3274 Liter | Standard Error 0.0298 |
| Heart Failure Participants | Interstitial Volume (ve) in Heart Failure Participants and Healthy Volunteers Before and Following Exercise | Post-exercise; Right lung apical | 0.3393 Liter | Standard Error 0.0301 |
| Heart Failure Participants | Interstitial Volume (ve) in Heart Failure Participants and Healthy Volunteers Before and Following Exercise | Pre-exercise; Left lung apical | 0.3126 Liter | Standard Error 0.0289 |
p-value: 0.015695% CI: [0.0236, 0.2061]ANOVA
p-value: 0.002695% CI: [0.0523, 0.2209]ANOVA
p-value: 0.032895% CI: [0.0094, 0.204]ANOVA
p-value: 0.015895% CI: [0.0235, 0.2056]ANOVA
p-value: 0.000295% CI: [0.0917, 0.2635]ANOVA
p-value: 0.065895% CI: [-0.0067, 0.1979]ANOVA
p-value: 0.01595% CI: [0.0251, 0.2137]ANOVA
p-value: 0.001595% CI: [0.0598, 0.2259]ANOVA
p-value: <0.000195% CI: [0.1057, 0.2496]ANOVA
p-value: 0.011495% CI: [0.0308, 0.2212]ANOVA
p-value: 0.000295% CI: [0.0774, 0.2153]ANOVA
p-value: <0.000195% CI: [0.1266, 0.3008]ANOVA
p-value: 0.02595% CI: [0.0151, 0.2071]ANOVA
p-value: 0.005295% CI: [0.0475, 0.2442]ANOVA
Secondary
Assessment of Intra-subject Variability in Ktrans Between Session 1 and Session 2 of DCE-MRI
Coefficient of variation (percentage) of intra-subject variability in Ktrans between Session 1 and Session 2 for total lung has been presented.
Time frame: Day 1 (Session 1) and Day 9 (Session 2)
Population: The Evaluable Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Healthy Volunteers | Assessment of Intra-subject Variability in Ktrans Between Session 1 and Session 2 of DCE-MRI | 32.4 Percentage |
| Heart Failure Participants | Assessment of Intra-subject Variability in Ktrans Between Session 1 and Session 2 of DCE-MRI | 41.3 Percentage |
Secondary
Assessment of Intra-subject Variability in Ve Between Session 1 and Session 2 of DCE-MRI
Coefficient of variation (percentage) of intra-subject variability in Ve between Session 1 and Session 2 for total lung has been presented.
Time frame: Day 1 (Session 1) and Day 9 (Session 2)
Population: The Evaluable Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Healthy Volunteers | Assessment of Intra-subject Variability in Ve Between Session 1 and Session 2 of DCE-MRI | 20.5 Percentage |
| Heart Failure Participants | Assessment of Intra-subject Variability in Ve Between Session 1 and Session 2 of DCE-MRI | 14.1 Percentage |