Hepatocellular CarcinomaNCT05068076
Role of Perfluorobutane in Lesion Detection, Targeting and Response Assessment for Ablation of HCC
A study testing Perfluorobutane in people with Hepatocellular Carcinoma and Microwave Ablation, run by Institute of Liver and Biliary Sciences, India at 1 site in India.
Trial summary
Primary liver cancers are the sixth most common malignancies worldwide, with hepatocellular carcinoma (HCC) accounting for approximately 80% of them. The Barcelona Clinic Liver Cancer (BCLC) classification is widely used in the management of HCC. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Hepatocellular Carcinoma, Microwave Ablation
- What is being tested?
- Perfluorobutane
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 21 participants
- Where
- 1 siteIndia
- Study dates
- 1 Oct 2021to 16 Dec 2021
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adult s (18 80 years) with HCC and who refused surgical resection
- Tumour number not more than five and the largest tumour size not larger than 5.0 cm;
- Ill defined lesions which are not easily detected on grey scale USG for lesion targeting.
- Liver function status at Child Pugh class A or B;
- East Coast Oncology Group (ECOG) performance status value 0 or 1;
- No severe coagulopathy (e.g. platelets ≥50,000/ prothrombin time ratio ≥ 50%).
- Available medical records and/or imaging studies.
Who cannot join
- Presence of vascular invasion and extrahepatic metastases at pre procedure imaging study;
- Ongoing anticoagulant treatment that cannot be stopped;
- Combined TACE and ablation for a larger lesion
Trial locations and contacts
1 site in 1 country.
India1 site
Institute of Liver & Biliary Sciences
New Delhi, National Capital Territory of Delhi, 110070
About this study
Official title: Role of Kupffer Phase Specific Ultrasound Contrast Agent (Perfluorobutane) in Lesion Detection, Targeting and Response Assessment for Ablation Therapy (Radiofrequency/ Microwave Ablation) of Hepatocellular Carcinoma
Primary liver cancers are the sixth most common malignancies worldwide, with hepatocellular carcinoma (HCC) accounting for approximately 80% of them. The Barcelona Clinic Liver Cancer (BCLC) classification is widely used in the management of HCC. At the time of diagnosis, fewer than 30% of the patients qualify for resection or transplant due to the large size or multiplicity of the lesions, background chronic liver disease, and other comorbidities.
However, the recent spread of surveillance has led to early detection of hepatocellular carcinoma (HCC), and the chance of receiving local treatment has increased. There are several options to treat small HCCs, including surgical resection, chemical ablation, transplantation, and percutaneous ablation (RFA/MWA).
Read more
Today, percutaneous ablation plays a key role in the treatment of early-stage HCC because it is less invasive than surgical resection and has a good efficacy. However, targeting of lesions under USG alone may be misleading as there may be an enhancing component which is not seen on plain ultrasound. To overcome this problem contrast enhanced ultrasound may be used intra-procedurally, however conventional ultrasound contrast agents show washout by 5 minutes from the system.
In this study, the investigators prospectively analyze patients undergoing ablation with the help of precise needle placement using a Kupffer phase ultrasound contrast agent (perfluorobutane) and their post procedure response assessment.
Read the detailed description
International status:
Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver with increasing incidence due to hepatitis B and C viruses . Ultrasound (USG) with, or without alpha feto-protein levels is a standard tool for surveillance of HCC. However, it leads to suboptimal detection rate and false referrals in the US . Use of an ultrasound contrast agent can be helpful in surveillance and diagnosis of focal liver lesions . Second generation ultrasound contrast agents like sulfur hexafluoride (SonoVue), perflutren lipid (Definity) and perfluorobutane (Sonazoid) are microbubbles composed of a phospholipid shell encompassing a low-solubility gas . The characteristic property of Sonazoid is its ability to accumulate in the reticuloendothelial system (such as the Kupffer cells in the liver) for a sustained period of time (up to 60 mins), which is not seen with other second generation contrast agents . Malignant liver lesions do not contain Kupffer cells so these lesions appear hypoechoic in the Kupffer phase (10-60 minutes) .
CEUS has been previously used for targeting of lesions for radiofrequency ablation, however the contrast agent used in the study was Definity . CEUS with Sonazoid has been frequently used in Japan, South Korea and Norway for diagnosis and surveillance. Diagnosis with Sonazoid involves the vascular phase (10 sec to 5 minutes) and the Kupffer phase (10-60 minutes). The vascular phase shows the tumor vascularity and the Kupffer phase shows the absence of reticuloendothelial cells in the lesion (2-4). In case of a new lesion detected in the Kupffer phase or a doubt regarding a previously detected lesion, defect reperfusion imaging can be done for confirmation and diagnosis . In a comparison between SonoVue and Sonazoid in diagnosis of liver lesions, Sonazoid was not inferior to SonoVue in diagnosis and significantly better in detecting lesions during whole liver scanning .
A study was done using Sonazoid enhanced ultrasound for targeting lesions not detected by conventional USG for ablation therapy, and it was found that CEUS detected 97% of the viable tumours compared to 83% by conventional USG. Furthermore, 93% of the lesions which were not detected on conventional USG were treated successfully using late phase of the contrast agent as a guiding tool . However, CEUS using Sonazoid was not used to assess treatment response in this study. A meta-analysis assessing the treatment response after radiofrequency ablation of HCC using CEUS concluded that technical success was higher with Sonazoid compared to other agents .
National status: A study evaluated the role of CEUS in guiding RFA of HCC, however the contrast used was SonoVue and no comparison was made of the post op CEUS with routine 1 month imaging .
The purpose of this study is to evaluate role of perfluorobutane in guiding ablation (RFA/MWA) of HCC and to compare treatment response two hours post procedure using the same ultrasound contrast agent with routine follow up CT/MRI at 1 month post procedure.
- Why this study- Sonazoid is available in only limited countries as of now (Japan, South Korea, Norway)
- So only limited efficacy studies have been done and none in India.
- Also, no study as yet has simultaneously evaluated role of Sonazoid in both lesion targeting as well as response assessment.
- Hypothesis- Immediate post-procedure CEUS with Sonazoid is not inferior to routine contrast CT/MRI at 1 month follow-up for response assessment.
- Conditions
- Hepatocellular Carcinoma, Microwave Ablation
- Being tested
- Perfluorobutane
- Medical subject headings
- Carcinoma, Hepatocellular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PerfluorobutaneDrug
Also called Sonazoid
Perfluorobutane enhanced ultrasound will be done prior to ablation of HCC and after 2hours post ablation and comparison will be done with 1 month post procedure CT/MRI
| Study group | Role | What they receive |
|---|---|---|
| Patients undergoing ablation for HCC | Experimental | Pre-procedure CEUS will be performed on patients undergoing ablation followed by targeting of lesions for precise needle placement in the Kupffer phase. 2 hours post procedure USG with contrast will also be done for response assessment Receives: Drug: Perfluorobutane |
What is being measured
The primary outcome is the main question the study is designed to answer.
Comparison of treatment response two hours post procedure with Perfluorobutane with routine CECT/CEMRI done at 1 month post procedure using modified RECIST criteria for HCC.
Post procedure CEUS will be done which will be compared with 1 month CECT/CEMRI to compare treatment response of ablation
Measured: upto 6 months
Secondary outcomes (1)
Targeting of lesions (fulfilling CEUS LIRADS 4/5 criteria) in the Kupffer phase for ablation
Lesions will be targeted in the Kupffer phase based on their appearance in the arterial and venous appearance which should fulfil CEUS LIRADS criteria for HCC. Part of the lesion showing maximum arterial enhancement will be targeted which can include a larger area than what is seen on gray scale USG alone. This will lead to better and complete ablation of the lesion.
Measured: upto 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Oct 2021
- Study start1 Oct 2021
- Primary completion16 Dec 2021
- Study completion16 Dec 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Hepatocellular CarcinomaStudies of the same condition, open and under way.
- More trials run by Institute of Liver and Biliary Sciences, IndiaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 21 participants (actual)
Sponsor and investigators
- Lead sponsor
- Institute of Liver and Biliary Sciences, India
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Amar Mukund, MBBS, MD, Study director, Institute of Liver & Biliary Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05068076
- Sponsor's protocol ID
- ILBS-HCC-04
- Status last verified
- Sep 2021
- First submitted
- 8 Sep 2021
- Last updated
- 21 Dec 2021
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Mukund A, Bansal A, Patidar Y, Thapar S, Sharma MK, Sarin SK. Role of contrast-enhanced ultrasound with Perfluorobutane in lesion detection, guidance for microwave ablation, and response assessment of hepatocellular carcinoma. Abdom Radiol (NY). 2022 Oct;47(10):3459-3467. doi: 10.1007/s00261-022-03609-y. Epub 2022 Jul 16.
PubMed 35842563
Study at a glance
From the registry record, last updated by the sponsor on 21 Dec 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Role of Kupffer Phase Specific Ultrasound Contrast Agent (Perfluorobutane) in Lesion Detection, Targeting and Response Assessment for Ablation Therapy (Radiofrequency/ Microwave Ablation) of Hepatocellular Carcinoma
- ClinicalTrials.gov ID
- NCT05068076
- Acronym / sponsor ID
- ILBS-HCC-04
- Conditions
- Hepatocellular Carcinoma, Microwave Ablation
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 21 participants (actual)
- Lead sponsor
- Institute of Liver and Biliary Sciences, IndiaUniversity, hospital or other
- Study start
- 1 Oct 2021 (actual)
- Primary completion
- 16 Dec 2021 (actual)
- Study completion
- 16 Dec 2021 (actual)
- First posted
- 5 Oct 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Primary liver cancers are the sixth most common malignancies worldwide, with hepatocellular carcinoma (HCC) accounting for approximately 80% of them. The Barcelona Clinic Liver Cancer (BCLC) classification is widely used in the management of HCC. At the time of diagnosis, fewer than 30% of the patients qualify for resection or transplant due to the large size or multiplicity of the lesions, background chronic liver disease, and other comorbidities.
However, the recent spread of surveillance has led to early detection of hepatocellular carcinoma (HCC), and the chance of receiving local treatment has increased. There are several options to treat small HCCs, including surgical resection, chemical ablation, transplantation, and percutaneous ablation (RFA/MWA).
Today, percutaneous ablation plays a key role in the treatment of early-stage HCC because it is less invasive than surgical resection and has a good efficacy. However, targeting of lesions under USG alone may be misleading as there may be an enhancing component which is not seen on plain ultrasound. To overcome this problem contrast enhanced ultrasound may be used intra-procedurally, however conventional ultrasound contrast agents show washout by 5 minutes from the system.
In this study, the investigators prospectively analyze patients undergoing ablation with the help of precise needle placement using a Kupffer phase ultrasound contrast agent (perfluorobutane) and their post procedure response assessment.
Detailed description
International status:
Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver with increasing incidence due to hepatitis B and C viruses . Ultrasound (USG) with, or without alpha feto-protein levels is a standard tool for surveillance of HCC. However, it leads to suboptimal detection rate and false referrals in the US . Use of an ultrasound contrast agent can be helpful in surveillance and diagnosis of focal liver lesions . Second generation ultrasound contrast agents like sulfur hexafluoride (SonoVue), perflutren lipid (Definity) and perfluorobutane (Sonazoid) are microbubbles composed of a phospholipid shell encompassing a low-solubility gas . The characteristic property of Sonazoid is its ability to accumulate in the reticuloendothelial system (such as the Kupffer cells in the liver) for a sustained period of time (up to 60 mins), which is not seen with other second generation contrast agents . Malignant liver lesions do not contain Kupffer cells so these lesions appear hypoechoic in the Kupffer phase (10-60 minutes) .
CEUS has been previously used for targeting of lesions for radiofrequency ablation, however the contrast agent used in the study was Definity . CEUS with Sonazoid has been frequently used in Japan, South Korea and Norway for diagnosis and surveillance. Diagnosis with Sonazoid involves the vascular phase (10 sec to 5 minutes) and the Kupffer phase (10-60 minutes). The vascular phase shows the tumor vascularity and the Kupffer phase shows the absence of reticuloendothelial cells in the lesion (2-4). In case of a new lesion detected in the Kupffer phase or a doubt regarding a previously detected lesion, defect reperfusion imaging can be done for confirmation and diagnosis . In a comparison between SonoVue and Sonazoid in diagnosis of liver lesions, Sonazoid was not inferior to SonoVue in diagnosis and significantly better in detecting lesions during whole liver scanning .
A study was done using Sonazoid enhanced ultrasound for targeting lesions not detected by conventional USG for ablation therapy, and it was found that CEUS detected 97% of the viable tumours compared to 83% by conventional USG. Furthermore, 93% of the lesions which were not detected on conventional USG were treated successfully using late phase of the contrast agent as a guiding tool . However, CEUS using Sonazoid was not used to assess treatment response in this study. A meta-analysis assessing the treatment response after radiofrequency ablation of HCC using CEUS concluded that technical success was higher with Sonazoid compared to other agents .
National status: A study evaluated the role of CEUS in guiding RFA of HCC, however the contrast used was SonoVue and no comparison was made of the post op CEUS with routine 1 month imaging .
The purpose of this study is to evaluate role of perfluorobutane in guiding ablation (RFA/MWA) of HCC and to compare treatment response two hours post procedure using the same ultrasound contrast agent with routine follow up CT/MRI at 1 month post procedure.
- Why this study- Sonazoid is available in only limited countries as of now (Japan, South Korea, Norway)
- So only limited efficacy studies have been done and none in India.
- Also, no study as yet has simultaneously evaluated role of Sonazoid in both lesion targeting as well as response assessment.
- Hypothesis- Immediate post-procedure CEUS with Sonazoid is not inferior to routine contrast CT/MRI at 1 month follow-up for response assessment.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Patients undergoing ablation for HCC | Experimental | Drug: PerfluorobutanePre-procedure CEUS will be performed on patients undergoing ablation followed by targeting of lesions for precise needle placement in the Kupffer phase. 2 hours post procedure USG with contrast will also be done for response assessment |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Adult s (18 80 years) with HCC and who refused surgical resection
- Tumour number not more than five and the largest tumour size not larger than 5.0 cm;
- Ill defined lesions which are not easily detected on grey scale USG for lesion targeting.
- Liver function status at Child Pugh class A or B;
- East Coast Oncology Group (ECOG) performance status value 0 or 1;
Key exclusion criteria (3 listed)
- Presence of vascular invasion and extrahepatic metastases at pre procedure imaging study;
- Ongoing anticoagulant treatment that cannot be stopped;
- Combined TACE and ablation for a larger lesion
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PerfluorobutaneAlso: SonazoidPerfluorobutane enhanced ultrasound will be done prior to ablation of HCC and after 2hours post ablation and comparison will be done with 1 month post procedure CT/MRI | Drug | Patients undergoing ablation for HCC |
Primary outcome
Comparison of treatment response two hours post procedure with Perfluorobutane with routine CECT/CEMRI done at 1 month post procedure using modified RECIST criteria for HCC.
Time frame: upto 6 months
Post procedure CEUS will be done which will be compared with 1 month CECT/CEMRI to compare treatment response of ablation
1 secondary outcome
Targeting of lesions (fulfilling CEUS LIRADS 4/5 criteria) in the Kupffer phase for ablation
Time frame: upto 6 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Dec 2021.
- Derived from this study: PubMed 35842563Mukund A, Bansal A, Patidar Y, Thapar S, Sharma MK, Sarin SK. Role of contrast-enhanced ultrasound with Perfluorobutane in lesion detection, guidance for microwave ablation, and response assessment of hepatocellular carcinoma. Abdom Radiol (NY). 2022 Oct;47(10):3459-3467. doi: 10.1007/s00261-022-03609-y. Epub 2022 Jul 16.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Amar Mukund, MBBS, MD study director
Institute of Liver & Biliary Sciences
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Perfluorobutane in people with Hepatocellular Carcinoma and Microwave Ablation, run by Institute of Liver and Biliary Sciences, India at 1 site in India.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 21 Dec 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in India. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Comparison of treatment response two hours post procedure with Perfluorobutane with routine CECT/CEMRI done at 1 month post procedure using modified RECIST criteria for HCC. (time frame: upto 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05068076, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Dec 2021.