Trial Outcomes & Findings for Noninvasive Subharmonic Aided Pressure Estimation of Portal Hypertension (NCT NCT02489045)

Last Updated: 2021-08-13

Results Overview

Evaluate the use of in vivo subharmonic aided pressure estimation (SHAPE as the difference between the optimized subharmonic signal in a hepatic vein and in the portal vein) as a first quantitative screening modality for determining the presence of clinically significant portal hypertension in patients undergoing a transjugular liver biopsy compared to catheter based hepatic-venous pressure gradient measurements (HVPG in mmHg as the reference standard).

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

178 participants

Primary outcome timeframe

up to 1 day

Results posted on

2021-08-13

Participant Flow

Participant milestones

Participant milestones
Measure	SHAPE Measurement 48 µl of Sonazoid microbubbles (GE Healthcare, Oslo, Norway) will be co-infused at a rate of 0.024 µl/kg body weight/minute together with a 0.9% NaCl solution infused at a rate of at least 2 ml/min. SHAPE measurement (Sonazoid ultrasoud contrast agent): Three vials with 48 µl of Sonazoid (GE Healthcare, Oslo, Norway) microbubbles (6 ml) will be prepared and drawn into a 10 ml syringe, placed in a syringe pump. Sonazoid will be co-infused at a rate of 0.024 µl/kg body weight/minute (suspension infusion rate of 0.18 ml/kg/hour) together with a 0.9% NaCl solution infused at a rate of at least 2 ml/min.
Overall Study STARTED	178
Overall Study COMPLETED	125
Overall Study NOT COMPLETED	53
Follow-up STARTED	21
Follow-up COMPLETED	11
Follow-up NOT COMPLETED	10

Reasons for withdrawal

Reasons for withdrawal
Measure	SHAPE Measurement 48 µl of Sonazoid microbubbles (GE Healthcare, Oslo, Norway) will be co-infused at a rate of 0.024 µl/kg body weight/minute together with a 0.9% NaCl solution infused at a rate of at least 2 ml/min. SHAPE measurement (Sonazoid ultrasoud contrast agent): Three vials with 48 µl of Sonazoid (GE Healthcare, Oslo, Norway) microbubbles (6 ml) will be prepared and drawn into a 10 ml syringe, placed in a syringe pump. Sonazoid will be co-infused at a rate of 0.024 µl/kg body weight/minute (suspension infusion rate of 0.18 ml/kg/hour) together with a 0.9% NaCl solution infused at a rate of at least 2 ml/min.
Overall Study unable to collect usable data	53
Follow-up Lost to Follow-up	10

Baseline Characteristics

Noninvasive Subharmonic Aided Pressure Estimation of Portal Hypertension

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	SHAPE Measurement n=125 Participants 48 µl of Sonazoid microbubbles (GE Healthcare, Oslo, Norway) will be co-infused at a rate of 0.024 µl/kg body weight/minute together with a 0.9% NaCl solution infused at a rate of at least 2 ml/min. SHAPE measurement (Sonazoid ultrasoud contrast agent): Three vials with 48 µl of Sonazoid (GE Healthcare, Oslo, Norway) microbubbles (6 ml) will be prepared and drawn into a 10 ml syringe, placed in a syringe pump. Sonazoid will be co-infused at a rate of 0.024 µl/kg body weight/minute (suspension infusion rate of 0.18 ml/kg/hour) together with a 0.9% NaCl solution infused at a rate of at least 2 ml/min.
Age, Continuous	58 years STANDARD_DEVIATION 12 • n=5 Participants
Sex: Female, Male Female	45 Participants n=5 Participants
Sex: Female, Male Male	80 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	4 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	121 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	5 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	41 Participants n=5 Participants
Race (NIH/OMB) White	79 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment United States	125 participants n=5 Participants

PRIMARY outcome

Timeframe: up to 1 day

Outcome measures

Outcome measures
Measure	SHAPE Measurement n=113 Participants 48 µl of Sonazoid microbubbles (GE Healthcare, Oslo, Norway) will be co-infused at a rate of 0.024 µl/kg body weight/minute together with a 0.9% NaCl solution infused at a rate of at least 2 ml/min. SHAPE measurement (Sonazoid ultrasoud contrast agent): Three vials with 48 µl of Sonazoid (GE Healthcare, Oslo, Norway) microbubbles (6 ml) will be prepared and drawn into a 10 ml syringe, placed in a syringe pump. Sonazoid will be co-infused at a rate of 0.024 µl/kg body weight/minute (suspension infusion rate of 0.18 ml/kg/hour) together with a 0.9% NaCl solution infused at a rate of at least 2 ml/min.
Diagnostic Accuracy of SHAPE Liver Pressure Estimates (in dB) for Diagnosing Portal Hypertension With Catheter Pressure Measurements (in mmHg) as the Reference Standard	95 diagnostic accuracy in percent

PRIMARY outcome

Timeframe: up to 1 day

Evaluate the correlation between in vivo subharmonic aided pressure estimation (SHAPE as the difference between the optimized subharmonic signal in a hepatic vein and catheter based hepatic-venous pressure gradient measurements (HVPG in mmHg) in patients undergoing a transjugular liver biopsy.

Outcome measures

Outcome measures
Measure	SHAPE Measurement n=113 Participants 48 µl of Sonazoid microbubbles (GE Healthcare, Oslo, Norway) will be co-infused at a rate of 0.024 µl/kg body weight/minute together with a 0.9% NaCl solution infused at a rate of at least 2 ml/min. SHAPE measurement (Sonazoid ultrasoud contrast agent): Three vials with 48 µl of Sonazoid (GE Healthcare, Oslo, Norway) microbubbles (6 ml) will be prepared and drawn into a 10 ml syringe, placed in a syringe pump. Sonazoid will be co-infused at a rate of 0.024 µl/kg body weight/minute (suspension infusion rate of 0.18 ml/kg/hour) together with a 0.9% NaCl solution infused at a rate of at least 2 ml/min.
SHAPE Liver Pressure Estimates (in dB) Correlation With Catheter Pressure Measurements (in mmHg)	0.68 correlation coefficient

PRIMARY outcome

Timeframe: up to 2 hours

Population: Only subjects with clinically significant portal hypertension were included in the follow-up study

Determine if SHAPE measurements (in dB) can provide a quantitative, noninvasive measurement of hepatic venous pressure gradient (HVPG) to monitor disease progression or treatment response in patients identified with portal hypertension by comparing the results to repeat biopsies and/or clinical outcomes.

Outcome measures

Outcome measures
Measure	SHAPE Measurement n=11 Participants 48 µl of Sonazoid microbubbles (GE Healthcare, Oslo, Norway) will be co-infused at a rate of 0.024 µl/kg body weight/minute together with a 0.9% NaCl solution infused at a rate of at least 2 ml/min. SHAPE measurement (Sonazoid ultrasoud contrast agent): Three vials with 48 µl of Sonazoid (GE Healthcare, Oslo, Norway) microbubbles (6 ml) will be prepared and drawn into a 10 ml syringe, placed in a syringe pump. Sonazoid will be co-infused at a rate of 0.024 µl/kg body weight/minute (suspension infusion rate of 0.18 ml/kg/hour) together with a 0.9% NaCl solution infused at a rate of at least 2 ml/min.
Comparing SHAPE Results With Blood Work and Concomitant Imaging in Portal Hypertension Patients SHAPE values in responders	-4.01 dB Standard Deviation 3.61
Comparing SHAPE Results With Blood Work and Concomitant Imaging in Portal Hypertension Patients SHAPE value in non-responders	2.33 dB Standard Deviation 0

Adverse Events

SHAPE Measurement

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Flemming Forsberg, PhD

Thomas Jefferson University

Phone: 215-955-4870

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place