Liver Disease ParenchymalLIMPIDNCT06231082
Bloody or Well Done. How Would You Like Your Liver Biopsy, Sir?
A study testing Group one - percutaneous (P) and Group two - EUS FNB (E) in people with Liver Disease Parenchymal, run by Carol Davila University of Medicine and Pharmacy at 1 site in Romania.
Trial summary
This is a randomized comparative trial between percutaneous liver biopsy and EUS FNB guided liver biopsy in patients with parenchymal liver disease. Studies so far have been shown that EUS FNB guided liver biopsy is non inferior to percutaneous liver biopsy in terms of efficacy, provided several conditions are met… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Liver Disease Parenchymal
- What is being tested?
- Group one - percutaneous (P) and Group two - EUS FNB (E)
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 78 participants
- Where
- 1 siteRomania
- Study dates
- 6 May 2024to Dec 2024
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Diffuse parenchymal liver disease with indication for liver biopsy for diagnostic and/or staging purposes,
- Eligibility for deep sedation with propofol
- Age above 18 years old
- Informed consent
Who cannot join
- Coagulation disorders which cannot be corrected
- Anticoagulant and/or antiagregant medication which cannot be stopped temporarily.
- Contraindications for liver biopsy, to local lidocaine anesthesia and to deep propofol sedation
- Absence of written informed consent
Trial locations and contacts
1 site in 1 country.
Romania1 site, 1 recruiting
- Recruiting
"Prof. Dr. Agrippa Ionescu" Clinical and Emerency Hospital
Bucharest, 0112013
Mihai Ciocirlan, Md, PhD, 0040722322625, ciocirlanm@yahoo.com
About this study
Official title: Bloody or Well Done. How Would You Like Your Liver Biopsy, Sir? Post Liver bIopsy abdoMinal PaIn as Predictive Factor for Liver bleeDing (LIMPID)
This is a randomized comparative trial between percutaneous liver biopsy and EUS FNB guided liver biopsy in patients with parenchymal liver disease.
Studies so far have been shown that EUS FNB guided liver biopsy is non inferior to percutaneous liver biopsy in terms of efficacy, provided several conditions are met (type of needle, wet suction, actuations).
Read more
În terms of safety, it may be that EUS FNB have an advantage, as needle diameter is slightly smaller, needle is inserted under better visualisation especially in patients with large subcutaneous fat tissue and the possibility of examining the needle tract and plugging it with needle content if needed ("the blood patch technique").
However, although severe, the incidence of liver bleeding is low, so a comparative trial with the hypothesis that EUS FNB has fewer liver bleedings than percutaneous techniques would have a very large sample size.
A recent study found out that abdominal pain at 2 hours after procedure is predictive for liver bleeding.
So we have design a randomized prospective trial assuming that EUS FNB guided liver biopsy has significantly less abdominal pain at 2 hours after procedure when compared to percutaneous route, using abdominal pain at 2 hours as a surrogate marker for risk of liver bleeding.
Read the detailed description
Why liver biopsy? Parenchymal liver diseases need sometimes diagnostic or staging assessment liver biopsy (eg. autoimmune hepatitis, primary biliary cholangitis, metabolic dysfunction associated fatty liver disease - MAFLD). Also, some focal liver lesions may need a diagnostic liver biopsy (eg. primitive liver tumors, liver metastases).
This can be performed percutaneously, trans-jugular and more recently trans-gastric or trans-duodenal under endoscopic ultrasound (EUS) guidance. The trans-jugular route was proposed for patients with coagulation disorders, as there is virtually no risk of bleeding, as the procedure is done within the supra-hepatic veins.
Currently, evidence exist that optimal results for EUS guided fine needle biopsy (FNB) are obtained by using a 19 Gauge Franseen FNB needle, by the heparin primed "wet suction" technique, with one or two passes (in both liver lobes), with at least 3 needle actuations [1,2,3,4]. Ensuring these conditions, the outcomes are non-inferior to percutaneous liver biopsy (length of the specimen, number of portal tracts, diagnostic accuracy).
So why choose EUS guided liver FNB? Two percutaneous liver biopsy adverse reactions are probably responsible for one's apprehension towards it - post procedure abdominal pain and the risk of liver bleeding. A recent meta-analysis [5] has found an incidence of mild abdominal pain at 12.9% and moderate-severe abdominal pain at 0.34%. The percentages for liver bleeding were 0.48% for major bleeding, 0.11% for major hematoma, 0.06% for hemoperitoneum and 0.01% for haemobilia (0.66% in total).
Bisonnette et al [6] have tried to find predictive factors for liver bleeding after percutaneous or trans-jugular liver biopsy. The only predictive factor was pain at 2h liver biopsy. This was more frequent following percutaneous than trans-jugular liver biopsy (33% vs. 15%; p < .001). Out of all patients with pain 2 h after liver biopsy, 15% had a liver biopsy-related bleeding, while out of those without pain 2 h after liver biopsy, 4% had a liver biopsy-related bleeding (p = .002). Pain 2 h after liver biopsy had a 55% (95% CI 0.35-0.73) sensitivity, 75% (95% CI 0.70-0.80) specificity, and 96% (95% CI 0.93-0.97) negative predictive value for liver biopsy -related bleeding.
EUS guided liver FNB seems to be safer than percutaneous liver biopsy. Eleven studies so far on 632 patients who had EUS FNB with 19G Franseen needle report on post procedure liver bleeding and abdominal pain [7-17]. Abdominal pain was present in 7.7%. of cases (28 of 362 reported patients), while liver bleeding was present in 0.16% (1 of 593, as "bile leak").
If we we're to design a study to prove that EUS guided liver FNB decreases bleeding rate from 0.66% for percutaneous route to 0.16%, with a type I error probability of 5% and a power of 80%, we would need to include 5126 patients, that is 2563 for each arm in a 1:1 allocation [7]. This is a near impossible study.
However, as Bisonnette et al [6] have proven, pain at 2h after liver biopsy is predictive for liver bleeding. So, we only need to prove that EUS guided liver FNB significantly decreases abdominal pain at 2h after procedure as compared to percutaneous route.
So, to prove that EUS guided liver FNB decreases abdominal pain rate at 2h after biopsy from 33% for percutaneous method to 7.7%, with a type I error probability of 5% and a power of 80%, we would need to include 78 patients, that is 39 for each arm in a 1:1 allocation [7].
Question of the research project We aim to answer the question whether EUS guided liver FNB has a significantly lower rate of abdominal pain at 2h after procedure than percutaneous liver biopsy.
Hypothesis The EUS guided liver FNB has a significantly lower rate of abdominal pain at 2h after procedure than percutaneous liver biopsy, which probably translates in a significantly lower liver bleeding rate.
Patients will be randomly allocated in one of the 2 study groups, following a randomization list (www.random.org), as it follows:
- Group one - percutaneous (P)
- Group two - EUS FNB (E)
Group one (P) - Percutaneous procedure will be performed under standard conditions, under transabdominal ultrasound guidance. After choosing the optimum needle trajectory, the skin site will be marked, standard skin sterilization with iodine and surgical draping of the site will be performed. Local anesthesia of the site with gradual lidocaine solution infiltration of the skin and underlying planes will be performed. Under ultrasound guidance, with collaboration of the patient for the respiratory movements, one or two passages with a 16G needle will be performed (BARD Max Core 16G, Becton Dickinson, USA). Specimens will be collected in formalin and send to pathology for processing.
Group two (E) - EUS guided liver FNB will be performed under deep sedation with propofol under anesthesiology monitoring. A 19G gauge Franseen needle (Acquire 19G, Boston Scientific, USA) will be used with the "wet suction" technique. Before inserting into the operating channel, the stylet will be removed, and the needle will be primed with heparin (500UI/5ml). After liver puncture, the 20ml aspiration syringe will be attached. Three needle actuations will be performed, one or two passes in the left liver lobe. At the end of the 3rd actuation, the syringe aspiration will be stopped, the needle will be left in place in the liver parenchyma for 2 to 3 minutes. The liver needle path will be examined with Doppler ultrasound to look for possible bleeding. If present, about 25% of the needle content will be pushed in the liver path, as previously described - the "blood patch" technique [19].
- Conditions
- Liver Disease Parenchymal
- Being tested
- Group one - percutaneous (P), Group two - EUS FNB (E)
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Group one - percutaneous (P)Procedure or surgery
Percutaneous procedure will be performed under standard conditions, under transabdominal ultrasound guidance. After choosing the optimum needle trajectory, the skin site will be marked, standard skin sterilization with iodine and surgical draping of the site will be performed. Local anesthesia of the site with gradual lidocaine solution infiltration of the skin and underlying planes will be performed. Under ultrasound guidance, with collaboration of the patient for the respiratory movements, one or two passages with a 16G needle will be performed (BARD Max Core 16G, Becton Dickinson, USA). Specimens will be collected in formalin and send to pathology for processing.
Group two - EUS FNB (E)Procedure or surgery
EUS guided liver FNB will be performed under deep sedation with propofol under anesthesiology monitoring. A 19G gauge Franseen needle (Acquire 19G, Boston Scientific, USA) will be used with the "wet suction" technique. Before inserting into the operating channel, the stylet will be removed, and the needle will be primed with heparin (500UI/5ml). After liver puncture, the 20ml aspiration syringe will be attached. Three needle actuations will be performed, one or two passes in the left liver lobe. At the end of the 3rd actuation, the syringe aspiration will be stopped, the needle will be left in place in the liver parenchyma for 2 to 3 minutes. The liver needle path will be examined with Doppler ultrasound to look for possible bleeding. If present, about 25% of the needle content will be pushed in the liver path, as previously described - the "blood patch" technique.
| Study group | Role | What they receive |
|---|---|---|
| Group one - percutaneous (P) | Active comparator | Percutaneous procedure will be performed under standard conditions, under transabdominal ultrasound guidance. After choosing the optimum needle trajectory, the skin site will be marked, standard skin sterilization with iodine and surgical draping of the site will be performed. Local anesthesia of the site with gradual lidocaine solution infiltration of the skin and underlying planes will be performed. Under ultrasound guidance, with collaboration of the patient for the respiratory movements, one or two passages with a 16G needle will be performed (BARD Max Core 16G, Becton Dickinson, USA). Specimens will be collected in formalin and send to pathology for processing. Receives: Procedure: Group one - percutaneous (P) |
| Group two - EUS FNB (E) | Active comparator | EUS guided liver FNB will be performed under deep sedation with propofol under anesthesiology monitoring. A 19G gauge Franseen needle (Acquire 19G, Boston Scientific, USA) will be used with the "wet suction" technique. Before inserting into the operating channel, the stylet will be removed, and the needle will be primed with heparin (500UI/5ml). After liver puncture, the 20ml aspiration syringe will be attached. Three needle actuations will be performed, one or two passes in the left liver lobe. At the end of the 3rd actuation, the syringe aspiration will be stopped, the needle will be left in place in the liver parenchyma for 2 to 3 minutes. The liver needle path will be examined with Doppler ultrasound to look for possible bleeding. If present, about 25% of the needle content will be pushed in the liver path, as previously described - the "blood patch" technique Receives: Procedure: Group two - EUS FNB (E) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Post procedure pain at 2 hours after procedure
Post procedure pain at 2 hours measured by Visual Analogue Scale (0 - 10)
Measured: 2 hours
Secondary outcomes (9)
Post procedure pain at 24 hours after procedure
Post procedure pain at 24 hours measured by Visual Analogue Scale (0 - 10)
Measured: 24 hours
Proportion of post procedure liver bleeding
Proportion of post procedure liver bleeding = number of patients with (perihepatic fluid, hemoperitoneum, liver hematoma, hemorrhagic shock) divided by the total number of patients enrolled in one arm
Measured: 7 days
Longest intact specimen
Length (mm) of the longest intact specimen removed by biopsy for one patient
Measured: 2 hours
Aggregate specimen length
Sum of the length of all the specimens (mm) removed by biopsy for one patient
Measured: 2 hours
Total number of specimens
Sum of the number of specimens removed by biopsy for one patient
Measured: 2 hours
Proportion of specimens > 20mm in aggregate length
Proportion of specimens > 20mm in aggregate length = number of patients with aggregate length of specimens (secondary outcome 5) > 20mm divided by the total number of patients enrolled in one arm
Measured: 2 hours
Total specimen complete portal tracts (CPT)
Sum of CPT for all specimens removed by biopsy for one patient
Measured: 28 days
Proportion of specimens with > 11 CPT
Proportion of specimens with > 11 CPT = number of patients with specimens > 11 CPT divided by the total number of patients in each arm
Measured: 28 days
Proportion of specimen with conclusive pathological diagnosis
Proportion of specimen with conclusive pathological diagnosis = number of patients with conclusive pathological diagnosis divided by the total number of patients in each arm
Measured: 28 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jan 2024
- Study start6 May 2024
- Primary completionDec 2024 (estimated)
- Study completionDec 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (18)Papers the sponsor has linked to this study.
- Other trials for Liver Disease ParenchymalStudies of the same condition, open and under way.
- 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 78 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Carol Davila University of Medicine and Pharmacy
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Mihai Ciocirlan, Carol Davila University of Medicine and Pharmacy
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06231082
- Sponsor's protocol ID
- LIMPID
- Acronym
- LIMPID
- Status last verified
- May 2024
- First submitted
- 9 Jan 2024
- Last updated
- 7 May 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Facciorusso A, Crino SF, Ramai D, Fabbri C, Mangiavillano B, Lisotti A, Muscatiello N, Cotsoglou C, Fusaroli P. Diagnostic yield of endoscopic ultrasound-guided liver biopsy in comparison to percutaneous liver biopsy: a systematic review and meta-analysis. Expert Rev Gastroenterol Hepatol. 2022 Jan;16(1):51-57. doi: 10.1080/17474124.2022.2020645. Epub 2021 Dec 29.
PubMed 34918578Zeng K, Jiang Z, Yang J, Chen K, Lu Q. Role of endoscopic ultrasound-guided liver biopsy: a meta-analysis. Scand J Gastroenterol. 2022 May;57(5):545-557. doi: 10.1080/00365521.2021.2025420. Epub 2022 Jan 20.
PubMed 35049405Chandan S, Deliwala S, Khan SR, Mohan BP, Dhindsa BS, Bapaye J, Goyal H, Kassab LL, Kamal F, Sayles HR, Kochhar GS, Adler DG. EUS-guided versus percutaneous liver biopsy: A comprehensive review and meta-analysis of outcomes. Endosc Ultrasound. 2023 Mar-Apr;12(2):171-180. doi: 10.4103/EUS-D-21-00268.
PubMed 36204798Laleman W, Vanderschueren E, Mehdi ZS, Wiest R, Cardenas A, Trebicka J. Endoscopic procedures in hepatology: Current trends and new developments. J Hepatol. 2024 Jan;80(1):124-139. doi: 10.1016/j.jhep.2023.08.032. Epub 2023 Sep 18.
PubMed 37730125Thomaides-Brears HB, Alkhouri N, Allende D, Harisinghani M, Noureddin M, Reau NS, French M, Pantoja C, Mouchti S, Cryer DRH. Incidence of Complications from Percutaneous Biopsy in Chronic Liver Disease: A Systematic Review and Meta-Analysis. Dig Dis Sci. 2022 Jul;67(7):3366-3394. doi: 10.1007/s10620-021-07089-w. Epub 2021 Jun 15.
PubMed 34129125Bissonnette J, Riescher-Tuczkiewicz A, Gigante E, Bourdin C, Boudaoud L, Soliman H, Durand F, Ronot M, Valla D, Vilgrain V, de Raucourt E, Rautou PE. Predicting bleeding after liver biopsy using comprehensive clinical and laboratory investigations: A prospective analysis of 302 procedures. J Thromb Haemost. 2022 Dec;20(12):2786-2796. doi: 10.1111/jth.15888. Epub 2022 Oct 5.
PubMed 36128757Ching-Companioni RA, Diehl DL, Johal AS, Confer BD, Khara HS. 19 G aspiration needle versus 19 G core biopsy needle for endoscopic ultrasound-guided liver biopsy: a prospective randomized trial. Endoscopy. 2019 Nov;51(11):1059-1065. doi: 10.1055/a-0956-6922. Epub 2019 Jul 23.
PubMed 31342474Nieto J, Dawod E, Deshmukh A, Penn E, Adler D, Saab S. EUS-guided fine-needle core liver biopsy with a modified one-pass, one-actuation wet suction technique comparing two types of EUS core needles. Endosc Int Open. 2020 Jul;8(7):E938-E943. doi: 10.1055/a-1165-1767. Epub 2020 Jun 16.
PubMed 32617398Aggarwal SN, Magdaleno T, Klocksieben F, MacFarlan JE, Goonewardene S, Zator Z, Shah S, Shah HN. A prospective, head-to-head comparison of 2 EUS-guided liver biopsy needles in vivo. Gastrointest Endosc. 2021 May;93(5):1133-1138. doi: 10.1016/j.gie.2020.09.050. Epub 2020 Oct 9.
PubMed 33045222Ching-Companioni RA, Johal AS, Confer BD, Forster E, Khara HS, Diehl DL. Single-pass 1-needle actuation versus single-pass 3-needle actuation technique for EUS-guided liver biopsy sampling: a randomized prospective trial (with video). Gastrointest Endosc. 2021 Sep;94(3):551-558. doi: 10.1016/j.gie.2021.03.023. Epub 2021 Mar 23.
PubMed 33771557Bang JY, Ward TJ, Guirguis S, Krall K, Contreras F, Jhala N, Navaneethan U, Hawes RH, Varadarajulu S. Radiology-guided percutaneous approach is superior to EUS for performing liver biopsies. Gut. 2021 Dec;70(12):2224-2226. doi: 10.1136/gutjnl-2021-324495. Epub 2021 Mar 25. No abstract available.
PubMed 33766911Hashimoto R, Lee DP, Samarasena JB, Chandan VS, Guo W, Lee JG, Chang KJ. Comparison of Two Specialized Histology Needles for Endoscopic Ultrasound (EUS)-Guided Liver Biopsy: A Pilot Study. Dig Dis Sci. 2021 May;66(5):1700-1706. doi: 10.1007/s10620-020-06391-3. Epub 2020 Jun 17.
PubMed 32556821Ali AH, Nallapeta NS, Yousaf MN, Petroski GF, Sharma N, Rao DS, Yin F, Davis RM, Bhat A, Swi AIA, Al-Juboori A, Ibdah JA, Hammoud GM. EUS-guided versus percutaneous liver biopsy: A prospective randomized clinical trial. Endosc Ultrasound. 2023 May-Jun;12(3):334-341. doi: 10.1097/eus.0000000000000010. Epub 2023 Jul 25.
PubMed 37693114Choi AY, Li X, Guo W, Chandan VS, Samarasena J, Lee JG, Chang KJ, Hu KQ. Performance of Endoscopic Ultrasound-Guided Versus Percutaneous Liver Biopsy in Diagnosing Stage 3-4 Fibrosis. Dig Dis Sci. 2023 Sep;68(9):3774-3780. doi: 10.1007/s10620-023-08019-8. Epub 2023 Aug 4.
PubMed 37540389Rai P, Majeed A, Kumar P, Rajput M, Goel A, Rao RN. Endoscopic ultrasound-guided liver biopsy using a single-pass, slow-pull technique with a 19-G Franseen tip fine-needle biopsy needle: A prospective study. Indian J Gastroenterol. 2023 Jun;42(3):418-424. doi: 10.1007/s12664-023-01339-7. Epub 2023 Apr 25.
PubMed 37097513
Study at a glance
From the registry record, last updated by the sponsor on 7 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Bloody or Well Done. How Would You Like Your Liver Biopsy, Sir? Post Liver bIopsy abdoMinal PaIn as Predictive Factor for Liver bleeDing (LIMPID)
- ClinicalTrials.gov ID
- NCT06231082
- Acronym / sponsor ID
- LIMPID / LIMPID
- Conditions
- Liver Disease Parenchymal
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 78 participants (estimated)
- Lead sponsor
- Carol Davila University of Medicine and PharmacyUniversity, hospital or other
- Study start
- 6 May 2024 (actual)
- Primary completion
- Dec 2024 (estimated)
- Study completion
- Dec 2024 (estimated)
- First posted
- 30 Jan 2024 (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.
This is a randomized comparative trial between percutaneous liver biopsy and EUS FNB guided liver biopsy in patients with parenchymal liver disease.
Studies so far have been shown that EUS FNB guided liver biopsy is non inferior to percutaneous liver biopsy in terms of efficacy, provided several conditions are met (type of needle, wet suction, actuations).
În terms of safety, it may be that EUS FNB have an advantage, as needle diameter is slightly smaller, needle is inserted under better visualisation especially in patients with large subcutaneous fat tissue and the possibility of examining the needle tract and plugging it with needle content if needed ("the blood patch technique").
However, although severe, the incidence of liver bleeding is low, so a comparative trial with the hypothesis that EUS FNB has fewer liver bleedings than percutaneous techniques would have a very large sample size.
A recent study found out that abdominal pain at 2 hours after procedure is predictive for liver bleeding.
So we have design a randomized prospective trial assuming that EUS FNB guided liver biopsy has significantly less abdominal pain at 2 hours after procedure when compared to percutaneous route, using abdominal pain at 2 hours as a surrogate marker for risk of liver bleeding.
Detailed description
Why liver biopsy? Parenchymal liver diseases need sometimes diagnostic or staging assessment liver biopsy (eg. autoimmune hepatitis, primary biliary cholangitis, metabolic dysfunction associated fatty liver disease - MAFLD). Also, some focal liver lesions may need a diagnostic liver biopsy (eg. primitive liver tumors, liver metastases).
This can be performed percutaneously, trans-jugular and more recently trans-gastric or trans-duodenal under endoscopic ultrasound (EUS) guidance. The trans-jugular route was proposed for patients with coagulation disorders, as there is virtually no risk of bleeding, as the procedure is done within the supra-hepatic veins.
Currently, evidence exist that optimal results for EUS guided fine needle biopsy (FNB) are obtained by using a 19 Gauge Franseen FNB needle, by the heparin primed "wet suction" technique, with one or two passes (in both liver lobes), with at least 3 needle actuations [1,2,3,4]. Ensuring these conditions, the outcomes are non-inferior to percutaneous liver biopsy (length of the specimen, number of portal tracts, diagnostic accuracy).
So why choose EUS guided liver FNB? Two percutaneous liver biopsy adverse reactions are probably responsible for one's apprehension towards it - post procedure abdominal pain and the risk of liver bleeding. A recent meta-analysis [5] has found an incidence of mild abdominal pain at 12.9% and moderate-severe abdominal pain at 0.34%. The percentages for liver bleeding were 0.48% for major bleeding, 0.11% for major hematoma, 0.06% for hemoperitoneum and 0.01% for haemobilia (0.66% in total).
Bisonnette et al [6] have tried to find predictive factors for liver bleeding after percutaneous or trans-jugular liver biopsy. The only predictive factor was pain at 2h liver biopsy. This was more frequent following percutaneous than trans-jugular liver biopsy (33% vs. 15%; p < .001). Out of all patients with pain 2 h after liver biopsy, 15% had a liver biopsy-related bleeding, while out of those without pain 2 h after liver biopsy, 4% had a liver biopsy-related bleeding (p = .002). Pain 2 h after liver biopsy had a 55% (95% CI 0.35-0.73) sensitivity, 75% (95% CI 0.70-0.80) specificity, and 96% (95% CI 0.93-0.97) negative predictive value for liver biopsy -related bleeding.
EUS guided liver FNB seems to be safer than percutaneous liver biopsy. Eleven studies so far on 632 patients who had EUS FNB with 19G Franseen needle report on post procedure liver bleeding and abdominal pain [7-17]. Abdominal pain was present in 7.7%. of cases (28 of 362 reported patients), while liver bleeding was present in 0.16% (1 of 593, as "bile leak").
If we we're to design a study to prove that EUS guided liver FNB decreases bleeding rate from 0.66% for percutaneous route to 0.16%, with a type I error probability of 5% and a power of 80%, we would need to include 5126 patients, that is 2563 for each arm in a 1:1 allocation [7]. This is a near impossible study.
However, as Bisonnette et al [6] have proven, pain at 2h after liver biopsy is predictive for liver bleeding. So, we only need to prove that EUS guided liver FNB significantly decreases abdominal pain at 2h after procedure as compared to percutaneous route.
So, to prove that EUS guided liver FNB decreases abdominal pain rate at 2h after biopsy from 33% for percutaneous method to 7.7%, with a type I error probability of 5% and a power of 80%, we would need to include 78 patients, that is 39 for each arm in a 1:1 allocation [7].
Question of the research project We aim to answer the question whether EUS guided liver FNB has a significantly lower rate of abdominal pain at 2h after procedure than percutaneous liver biopsy.
Hypothesis The EUS guided liver FNB has a significantly lower rate of abdominal pain at 2h after procedure than percutaneous liver biopsy, which probably translates in a significantly lower liver bleeding rate.
Patients will be randomly allocated in one of the 2 study groups, following a randomization list (www.random.org), as it follows:
- Group one - percutaneous (P)
- Group two - EUS FNB (E)
Group one (P) - Percutaneous procedure will be performed under standard conditions, under transabdominal ultrasound guidance. After choosing the optimum needle trajectory, the skin site will be marked, standard skin sterilization with iodine and surgical draping of the site will be performed. Local anesthesia of the site with gradual lidocaine solution infiltration of the skin and underlying planes will be performed. Under ultrasound guidance, with collaboration of the patient for the respiratory movements, one or two passages with a 16G needle will be performed (BARD Max Core 16G, Becton Dickinson, USA). Specimens will be collected in formalin and send to pathology for processing.
Group two (E) - EUS guided liver FNB will be performed under deep sedation with propofol under anesthesiology monitoring. A 19G gauge Franseen needle (Acquire 19G, Boston Scientific, USA) will be used with the "wet suction" technique. Before inserting into the operating channel, the stylet will be removed, and the needle will be primed with heparin (500UI/5ml). After liver puncture, the 20ml aspiration syringe will be attached. Three needle actuations will be performed, one or two passes in the left liver lobe. At the end of the 3rd actuation, the syringe aspiration will be stopped, the needle will be left in place in the liver parenchyma for 2 to 3 minutes. The liver needle path will be examined with Doppler ultrasound to look for possible bleeding. If present, about 25% of the needle content will be pushed in the liver path, as previously described - the "blood patch" technique [19].
Study design
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Group one - percutaneous (P) | Active comparator | Procedure: Group one - percutaneous (P)Percutaneous procedure will be performed under standard conditions, under transabdominal ultrasound guidance. After choosing the optimum needle trajectory, the skin site will be marked, standard skin sterilization with iodine and surgical draping of the site will be performed. Local anesthesia of the site with gradual lidocaine solution infiltration of the skin and underlying planes will be performed. Under ultrasound guidance, with collaboration of the patient for the respiratory movements, one or two passages with a 16G needle will be performed (BARD Max Core 16G, Becton Dickinson, USA). Specimens will be collected in formalin and send to pathology for processing. |
| Group two - EUS FNB (E) | Active comparator | Procedure: Group two - EUS FNB (E)EUS guided liver FNB will be performed under deep sedation with propofol under anesthesiology monitoring. A 19G gauge Franseen needle (Acquire 19G, Boston Scientific, USA) will be used with the "wet suction" technique. Before inserting into the operating channel, the stylet will be removed, and the needle will be primed with heparin (500UI/5ml). After liver puncture, the 20ml aspiration syringe will be attached. Three needle actuations will be performed, one or two passes in the left liver lobe. At the end of the 3rd actuation, the syringe aspiration will be stopped, the needle will be left in place in the liver parenchyma for 2 to 3 minutes. The liver needle path will be examined with Doppler ultrasound to look for possible bleeding. If present, about 25% of the needle content will be pushed in the liver path, as previously described - the "blood patch" technique |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Diffuse parenchymal liver disease with indication for liver biopsy for diagnostic and/or staging purposes,
- Eligibility for deep sedation with propofol
- Age above 18 years old
- Informed consent
Key exclusion criteria (4 listed)
- Coagulation disorders which cannot be corrected
- Anticoagulant and/or antiagregant medication which cannot be stopped temporarily.
- Contraindications for liver biopsy, to local lidocaine anesthesia and to deep propofol sedation
- Absence of written informed consent
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 |
|---|---|---|
| Group one - percutaneous (P)Percutaneous procedure will be performed under standard conditions, under transabdominal ultrasound guidance. After choosing the optimum needle trajectory, the skin site will be marked, standard skin sterilization with iodine and surgical draping of the site will be performed. Local anesthesia of the site with gradual lidocaine solution infiltration of the skin and underlying planes will be performed. Under ultrasound guidance, with collaboration of the patient for the respiratory movements, one or two passages with a 16G needle will be performed (BARD Max Core 16G, Becton Dickinson, USA). Specimens will be collected in formalin and send to pathology for processing. | Procedure or surgery | Group one - percutaneous (P) |
| Group two - EUS FNB (E)EUS guided liver FNB will be performed under deep sedation with propofol under anesthesiology monitoring. A 19G gauge Franseen needle (Acquire 19G, Boston Scientific, USA) will be used with the "wet suction" technique. Before inserting into the operating channel, the stylet will be removed, and the needle will be primed with heparin (500UI/5ml). After liver puncture, the 20ml aspiration syringe will be attached. Three needle actuations will be performed, one or two passes in the left liver lobe. At the end of the 3rd actuation, the syringe aspiration will be stopped, the needle will be left in place in the liver parenchyma for 2 to 3 minutes. The liver needle path will be examined with Doppler ultrasound to look for possible bleeding. If present, about 25% of the needle content will be pushed in the liver path, as previously described - the "blood patch" technique. | Procedure or surgery | Group two - EUS FNB (E) |
Primary outcome
Post procedure pain at 2 hours after procedure
Time frame: 2 hours
Post procedure pain at 2 hours measured by Visual Analogue Scale (0 - 10)
9 secondary outcomes
Post procedure pain at 24 hours after procedure
Time frame: 24 hours
Proportion of post procedure liver bleeding
Time frame: 7 days
Longest intact specimen
Time frame: 2 hours
Aggregate specimen length
Time frame: 2 hours
Total number of specimens
Time frame: 2 hours
Proportion of specimens > 20mm in aggregate length
Time frame: 2 hours
Total specimen complete portal tracts (CPT)
Time frame: 28 days
Proportion of specimens with > 11 CPT
Time frame: 28 days
Proportion of specimen with conclusive pathological diagnosis
Time frame: 28 days
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 May 2024.
- Background: PubMed 34918578Facciorusso A, Crino SF, Ramai D, Fabbri C, Mangiavillano B, Lisotti A, Muscatiello N, Cotsoglou C, Fusaroli P. Diagnostic yield of endoscopic ultrasound-guided liver biopsy in comparison to percutaneous liver biopsy: a systematic review and meta-analysis. Expert Rev Gastroenterol Hepatol. 2022 Jan;16(1):51-57. doi: 10.1080/17474124.2022.2020645. Epub 2021 Dec 29.
- Background: PubMed 35049405Zeng K, Jiang Z, Yang J, Chen K, Lu Q. Role of endoscopic ultrasound-guided liver biopsy: a meta-analysis. Scand J Gastroenterol. 2022 May;57(5):545-557. doi: 10.1080/00365521.2021.2025420. Epub 2022 Jan 20.
- Background: PubMed 36204798Chandan S, Deliwala S, Khan SR, Mohan BP, Dhindsa BS, Bapaye J, Goyal H, Kassab LL, Kamal F, Sayles HR, Kochhar GS, Adler DG. EUS-guided versus percutaneous liver biopsy: A comprehensive review and meta-analysis of outcomes. Endosc Ultrasound. 2023 Mar-Apr;12(2):171-180. doi: 10.4103/EUS-D-21-00268.
- Background: PubMed 37730125Laleman W, Vanderschueren E, Mehdi ZS, Wiest R, Cardenas A, Trebicka J. Endoscopic procedures in hepatology: Current trends and new developments. J Hepatol. 2024 Jan;80(1):124-139. doi: 10.1016/j.jhep.2023.08.032. Epub 2023 Sep 18.
- Background: PubMed 34129125Thomaides-Brears HB, Alkhouri N, Allende D, Harisinghani M, Noureddin M, Reau NS, French M, Pantoja C, Mouchti S, Cryer DRH. Incidence of Complications from Percutaneous Biopsy in Chronic Liver Disease: A Systematic Review and Meta-Analysis. Dig Dis Sci. 2022 Jul;67(7):3366-3394. doi: 10.1007/s10620-021-07089-w. Epub 2021 Jun 15.
- Background: PubMed 36128757Bissonnette J, Riescher-Tuczkiewicz A, Gigante E, Bourdin C, Boudaoud L, Soliman H, Durand F, Ronot M, Valla D, Vilgrain V, de Raucourt E, Rautou PE. Predicting bleeding after liver biopsy using comprehensive clinical and laboratory investigations: A prospective analysis of 302 procedures. J Thromb Haemost. 2022 Dec;20(12):2786-2796. doi: 10.1111/jth.15888. Epub 2022 Oct 5.
- Background: PubMed 31342474Ching-Companioni RA, Diehl DL, Johal AS, Confer BD, Khara HS. 19 G aspiration needle versus 19 G core biopsy needle for endoscopic ultrasound-guided liver biopsy: a prospective randomized trial. Endoscopy. 2019 Nov;51(11):1059-1065. doi: 10.1055/a-0956-6922. Epub 2019 Jul 23.
- Background: PubMed 32617398Nieto J, Dawod E, Deshmukh A, Penn E, Adler D, Saab S. EUS-guided fine-needle core liver biopsy with a modified one-pass, one-actuation wet suction technique comparing two types of EUS core needles. Endosc Int Open. 2020 Jul;8(7):E938-E943. doi: 10.1055/a-1165-1767. Epub 2020 Jun 16.
- Background: PubMed 33045222Aggarwal SN, Magdaleno T, Klocksieben F, MacFarlan JE, Goonewardene S, Zator Z, Shah S, Shah HN. A prospective, head-to-head comparison of 2 EUS-guided liver biopsy needles in vivo. Gastrointest Endosc. 2021 May;93(5):1133-1138. doi: 10.1016/j.gie.2020.09.050. Epub 2020 Oct 9.
- Background: PubMed 33771557Ching-Companioni RA, Johal AS, Confer BD, Forster E, Khara HS, Diehl DL. Single-pass 1-needle actuation versus single-pass 3-needle actuation technique for EUS-guided liver biopsy sampling: a randomized prospective trial (with video). Gastrointest Endosc. 2021 Sep;94(3):551-558. doi: 10.1016/j.gie.2021.03.023. Epub 2021 Mar 23.
- Background: PubMed 33766911Bang JY, Ward TJ, Guirguis S, Krall K, Contreras F, Jhala N, Navaneethan U, Hawes RH, Varadarajulu S. Radiology-guided percutaneous approach is superior to EUS for performing liver biopsies. Gut. 2021 Dec;70(12):2224-2226. doi: 10.1136/gutjnl-2021-324495. Epub 2021 Mar 25. No abstract available.
- Background: PubMed 32556821Hashimoto R, Lee DP, Samarasena JB, Chandan VS, Guo W, Lee JG, Chang KJ. Comparison of Two Specialized Histology Needles for Endoscopic Ultrasound (EUS)-Guided Liver Biopsy: A Pilot Study. Dig Dis Sci. 2021 May;66(5):1700-1706. doi: 10.1007/s10620-020-06391-3. Epub 2020 Jun 17.
- 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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Group one - percutaneous (P) and Group two - EUS FNB (E) in people with Liver Disease Parenchymal, run by Carol Davila University of Medicine and Pharmacy at 1 site in Romania.
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 4 inclusion and 4 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: status not confirmed, as of the sponsor's last update on 7 May 2024. 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 Romania. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Mihai Ciocirlan (0040722322625, ciocirlanm@yahoo.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Post procedure pain at 2 hours after procedure (time frame: 2 hours). 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 NCT06231082, which also lists 18 linked publications.
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 7 May 2024.