Trial Outcomes & Findings for Ultrasound Liver Intraoperative Imaging With SonoVue® (NCT NCT01880554)

Last Updated: 2025-09-03

Results Overview

The clinical utility will be evaluated in terms of justified modification of the surgical procedure following contrast-enhanced intra-operative ultrasound (CE-IOUS), compared to the surgical procedure following conventional intra-operative ultrasound. For each patient, we will consider CE-IOUS to be clinically useful: * if the surgical procedure envisaged at the end of the CE-IOUS is different from the surgical procedure envisaged at the end of the conventional ultrasound * and if the surgical procedure envisaged at the end of the CE-IOUS is justified We reported the percentage of patients for whom there was a modified and justified surgical gesture following CE-IOUS.

Recruitment status

COMPLETED

Study phase

Target enrollment

68 participants

Primary outcome timeframe

At time of surgery

Results posted on

2025-09-03

Participant Flow

Participant milestones

Participant milestones
Measure	Contrast-enhanced Intraoperative Ultrasound Contrast-enhanced intraoperative ultrasound Contrast-enhanced intraoperative ultrasound: Once the patient is included in the study, a staging procedure is performed in three stages before hepatic metastases treatment: Step # 1 preoperative (maximum 8 weeks before surgery Steps # 2 and # 3 intraoperative performed by the same surgeon in 2 stages
Overall Study STARTED	68
Overall Study Population Eligible	58
Overall Study Population Eligible and Assessable	54
Overall Study COMPLETED	52
Overall Study NOT COMPLETED	16

Reasons for withdrawal

Reasons for withdrawal
Measure	Contrast-enhanced Intraoperative Ultrasound Contrast-enhanced intraoperative ultrasound Contrast-enhanced intraoperative ultrasound: Once the patient is included in the study, a staging procedure is performed in three stages before hepatic metastases treatment: Step # 1 preoperative (maximum 8 weeks before surgery Steps # 2 and # 3 intraoperative performed by the same surgeon in 2 stages
Overall Study Protocol Violation	14
Overall Study Simon's design requirements	2

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Contrast-enhanced Intraoperative Ultrasound n=52 Participants Contrast-enhanced intraoperative ultrasound Contrast-enhanced intraoperative ultrasound: Once the patient is included in the study, a staging procedure is performed in three stages before hepatic metastases treatment: Step # 1 preoperative (maximum 8 weeks before surgery Steps # 2 and # 3 intraoperative performed by the same surgeon in 2 stages
Age, Continuous	62.8 years STANDARD_DEVIATION 11.0 • n=52 Participants
Sex: Female, Male Female	17 Participants n=52 Participants
Sex: Female, Male Male	35 Participants n=52 Participants
Cancer localization Right Colon	11 Participants n=52 Participants
Cancer localization Left Colon	22 Participants n=52 Participants
Cancer localization Transverse Colon	2 Participants n=52 Participants
Cancer localization Rectum	17 Participants n=52 Participants
Liver metastases Synchronous	29 Participants n=52 Participants
Liver metastases Metachronous	23 Participants n=52 Participants

PRIMARY outcome

Timeframe: At time of surgery

Population: We used a 2-stage Simon's design with the following assumptions: * maximum tolerated futility rate: 5%, * expected minimum utility rate: 15%, * Type I error of 10%, * power of 85%. Thus, 52 eligible and evaluable patients were required (25 in the first stage). First stage: stop, if CE-IOUS is not deemed clinically useful for at least one patient (4.0%). Second stage: CE-IOUS clinically useful if the planned surgical procedure is modified and justified for 5 or more patients (9.6%).

Outcome measures

Outcome measures
Measure	Contrast-enhanced Intraoperative Ultrasound n=52 Participants Contrast-enhanced intraoperative ultrasound Contrast-enhanced intraoperative ultrasound: Once the patient is included in the study, a staging procedure is performed in three stages before hepatic metastases treatment: Step # 1 preoperative (maximum 8 weeks before surgery Steps # 2 and # 3 intraoperative performed by the same surgeon in 2 stages. Step #2 intraoperative ultrasound and step #3 Contrast-enhanced intraoperative ultrasound
Clinical Utility of Intraoperative Contrast Ultrasound in the Surgery of Colorectal Cancer Liver Metastases.	7.7 percentage of patients Interval 3.2 to 18.6

SECONDARY outcome

Timeframe: at time of surgery

Population: Subgroup of patients with preoperative chemotherapy

The primary endpoint will be assessed in the subgroup of patients who received preoperative chemotherapy. As for the primary outcome, the clinical utility is evaluated in terms of justified modification of the surgical gesture envisaged following CE-IOUS, compared to the surgical gesture envisaged following a conventional intraoperative ultrasound. We reported the percentage of patients for whom there was a modified and justified surgical gesture following CE-IOUS in the subgroup of patients who received preoperative chemotherapy.

Outcome measures

Outcome measures
Measure	Contrast-enhanced Intraoperative Ultrasound n=41 Participants Contrast-enhanced intraoperative ultrasound Contrast-enhanced intraoperative ultrasound: Once the patient is included in the study, a staging procedure is performed in three stages before hepatic metastases treatment: Step # 1 preoperative (maximum 8 weeks before surgery Steps # 2 and # 3 intraoperative performed by the same surgeon in 2 stages. Step #2 intraoperative ultrasound and step #3 Contrast-enhanced intraoperative ultrasound
Clinical Utility of CE-IOUS in Subgroup of Patients Who Received Preoperative Chemotherapy	7.31 percentage of patients Interval 2.52 to 19.43

SECONDARY outcome

Timeframe: up to 3 months after surgery

Population: There were 22 (40.7%) out of 54 chemotherapy-free patients within 3 post-operative months

Detection of malignant lesions by CE-IOUS in chemotherapy-free patients within 3 post-operative months. The detection rate is defined as the proportion of malignant lesions for which there is concordance between the diagnosis established by CE-IOUS and the reference examination.

Outcome measures

Outcome measures
Measure	Contrast-enhanced Intraoperative Ultrasound n=22 Participants Contrast-enhanced intraoperative ultrasound Contrast-enhanced intraoperative ultrasound: Once the patient is included in the study, a staging procedure is performed in three stages before hepatic metastases treatment: Step # 1 preoperative (maximum 8 weeks before surgery Steps # 2 and # 3 intraoperative performed by the same surgeon in 2 stages. Step #2 intraoperative ultrasound and step #3 Contrast-enhanced intraoperative ultrasound
Performance Evaluation of Intraoperative Ultrasound Contrast: Detection Rate Per Lesion	0.75 proportion of lesions

SECONDARY outcome

Timeframe: At time of contrast-enhanced IOUS

Description of technical arrangements for the CE-IOUS duration. The length of time during which contrast injection was useable.

Outcome measures

Outcome measures
Measure	Contrast-enhanced Intraoperative Ultrasound n=54 Participants Contrast-enhanced intraoperative ultrasound Contrast-enhanced intraoperative ultrasound: Once the patient is included in the study, a staging procedure is performed in three stages before hepatic metastases treatment: Step # 1 preoperative (maximum 8 weeks before surgery Steps # 2 and # 3 intraoperative performed by the same surgeon in 2 stages. Step #2 intraoperative ultrasound and step #3 Contrast-enhanced intraoperative ultrasound
Description of Technical Arrangements for the CE-IOUS	225 seconds Interval 105.0 to 307.0

SECONDARY outcome

Timeframe: up to 3 months after surgery

Characterisation rate for focal liver lesions: the proportion of lesions whose nature on CE-IOUS is identical to the nature of the lesions defined by the reference examinations among all the lesions seen on CE-IOUS (malignant and benign)

Outcome measures

Outcome measures
Measure	Contrast-enhanced Intraoperative Ultrasound n=54 Participants Contrast-enhanced intraoperative ultrasound Contrast-enhanced intraoperative ultrasound: Once the patient is included in the study, a staging procedure is performed in three stages before hepatic metastases treatment: Step # 1 preoperative (maximum 8 weeks before surgery Steps # 2 and # 3 intraoperative performed by the same surgeon in 2 stages. Step #2 intraoperative ultrasound and step #3 Contrast-enhanced intraoperative ultrasound
Performance Evaluation of Intraoperative Ultrasound Contrast Per Lesion: Characterisation Rate	0.94 proportion of lesions

Adverse Events

Contrast-enhanced Intraoperative Ultrasound

Serious events: 11 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Contrast-enhanced Intraoperative Ultrasound n=54 participants at risk Contrast-enhanced intraoperative ultrasound Contrast-enhanced intraoperative ultrasound: Once the patient is included in the study, a staging procedure is performed in three stages before hepatic metastases treatment: Step # 1 preoperative (maximum 8 weeks before surgery Steps # 2 and # 3 intraoperative performed by the same surgeon in 2 stages
Infections and infestations Peritonitis	3.7% 2/54
Vascular disorders Hypertension	1.9% 1/54
Surgical and medical procedures Eventration	1.9% 1/54
Hepatobiliary disorders Biliary fistula	3.7% 2/54
Respiratory, thoracic and mediastinal disorders Pleural effusion	3.7% 2/54
Hepatobiliary disorders Bile collection secondary to a biliary tract wound	1.9% 1/54
Gastrointestinal disorders Fistule anastomose colorectale	1.9% 1/54
Hepatobiliary disorders Hepatic failure	1.9% 1/54
Vascular disorders Peri-hepatic Blood Collection	1.9% 1/54
Infections and infestations Stercoral peritonitis	1.9% 1/54
General disorders Asthenia	1.9% 1/54
Respiratory, thoracic and mediastinal disorders Right cry	1.9% 1/54
Gastrointestinal disorders Acute pancreatitis	1.9% 1/54

Other adverse events

Other adverse events
Measure	Contrast-enhanced Intraoperative Ultrasound n=54 participants at risk Contrast-enhanced intraoperative ultrasound Contrast-enhanced intraoperative ultrasound: Once the patient is included in the study, a staging procedure is performed in three stages before hepatic metastases treatment: Step # 1 preoperative (maximum 8 weeks before surgery Steps # 2 and # 3 intraoperative performed by the same surgeon in 2 stages
Blood and lymphatic system disorders Anemia	1.9% 1/54
Hepatobiliary disorders Hepatocellular insufficiency	1.9% 1/54

Additional Information

Derek Dinart

Institut Bergonie

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place