Condition category
Date applied
Date assigned
Last edited
Retrospectively registered
Overall trial status
Recruitment status
No longer recruiting
Publication status
Results overdue

Plain English Summary

Not provided at time of registration

Trial website

Contact information



Primary contact

Prof Javier Padillo


Contact details

Servicio De Cirugia General
3ª Planta De Hospital General
Ala Norte
Hospital Universitario Virgen Del Rocio
C/ Manuel Siurot S/N

Additional identifiers

EudraCT number

2009-017793-20 number

Protocol/serial number


Study information

Scientific title

Infusion of intraportal autologus mononuclear bone marrow cells as a liver regeneration enhancer prior to extended hepatectomy. A randomised, open-label multicentre phase II clinical trial



Study hypothesis

Autotransplanting autologous mononuclear bone marrow cells might enhance hepatic regeneration, administered intraportally prior to surgery, in patients with a hepatic space occupying lesion (SOL) which need an extended hepatic resection (more than five segments) and in which the residual hepatic volume is insufficient to guarantee hepatic function and the necessary safety margins following the resection.

Ethics approval

Autonomous Clinical Trials Committee of Andalusia
Clinical Research Ethics Committee at University Hospital Virgen del Rocio
Ethics Committee at University Hospital Valme, Seville

Study design

Prospective multicentre open-label randomised and controlled phase II clinical trial

Primary study design


Secondary study design

Randomised controlled trial

Trial setting


Trial type


Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet


Use of stem cells in hepatic resection due to hepatic space occupying lesions


1. Control group: right hepatic portal embolization
2. Study group: right hepatic portal embolization plus infusion of stem cells. Generic drug name: mononuclear bone marrow stem cells
3. Dosage given: 2.000 x 106 cells
4. Method and frequency of administration: intraportal infusion in a single administration
5. Follow up for all treatment arms: 12 months

Intervention type



Phase II

Drug names

Primary outcome measure

1. Adverse events and serious adverse events in the first 24 hours of administering the BM-MNCs, and observed in the follow ups at 2, 4 and 6 weeks following cell therapy administration
2. Assessment of the hepatic volume via computed tomography (CT) (10 mm thick axial helical CT with 10 mm reconstruction) at 2, 4 and 6 weeks following the administration of cell therapy (until 8 weeks in cyrrhotic patients):
2.1. In each axial section: volume (cm3) = Area (cm2) x reconstruction index (cm)
2.2. The volumes are calculated by totalling the areas of each cut
3. The following parameters are used:
3.1. Total hepatic volume (THV)
3.2. Residual hepatic volume (RHV)
3.3. Percentage THV / RHV

Secondary outcome measures

1. Duration of hepatic regeneration (days)
2. Percentage of patients that can be fully operated on
3. Time since [falling ill]
4. Assessment of the hepatic regeneration response:
4.1. TNF-a, interleukina 2, interleukina 6
4.2. Hepatocyte Growth Factor (HGF)
4.3. Epidermal Growth Factor (EGF)
4.4. Transforming Growth Factor Alpha (TGF-a)
4.5. Insulinaemia
4.6. Metanephrines (urine)
5. Inherent post-operative complications regarding the residual hepatic volume (degree of liver failure: Model fo End stage Liver Disease - MELD)
6. Resection margins free from tumours
7. Structured histological assessment of the regenerated hepatic tissue and of the degree of fibrosis

Overall trial start date


Overall trial end date


Reason abandoned (if study stopped)


Participant inclusion criteria

1. Patients of both sexes aged between 18 and 70
2. Normal analytical parameters, defined by:
2.1. Leukocytes higher than 3,000
2.2. Neutrophils higher than 1,500
2.3. Platelets higher than 100,000
2.4. AST/ALT less than 1.5 standard institutional range
2.5. Creatinine less than 1.5 mg/dl
3. Patients with a hepatic space occupying lesion (SOL) which need an extended hepatic resection (of more than five segments)
4. The selection must be careful and basically include 4 types of hepatic lesions which must previously be submitted to a hepatic volumetry:
4.1. Metastatic disease susceptible to extended right hepatectomy in segment IV
4.2. Metastatic disease susceptible to right hepatectomy with suspected liver disease(neoadjuvant chemotherapy) (when hepatic function is unclear, the indocyanine green test can be used)
4.3. Bilobar hepatic metastases with multiple nodules in the right lobe, and more than 3 nodules bigger than 30mm in the left hepatic lobe (LHL): tumourectomy of the LHL + ligature of the right portal branch (or post-operative percutaneous embolisation) with a view to carry out a right hepatectomy 4-6 weeks afterwards (two-stage surgery)
4.4. Hepatocarcinoma susceptible to extended right hepatectomy
4.5. Benign Hepatic Lesions (Haemangiomas, Hydatid Cysts, or Primary Hepatic Tumours/Hepatoblastoma), which because of their extension put the viability of the remaining hepatic tissue at risk
5. The pre-operative assessment of the residual hepatic volume should be, following the hepatectomy >30% (>40% in diseased livers)
6. The following definitions/measurements/factors should be included in the evaluation:
6.1. Total hepatic volume: residual hepatic volume (RHV) + resectable hepatic volume
6.2. Resectable hepatic volume: includes the volume of the tumoral lesions plus the surrounding hepatic parenchyma with compromised vascular structures
6.3. Functional hepatic volume: is the difference between the THV and the volume of the lesions
6.4. Residual Hepatic Volume: Terminal Hepatic Volume (THV) - Hepatic Volume (HV) to be resected
7. Patients who give their informed, written consent in order to participate in the study and offer sufficient guarantees regarding their adhesion to the protocol, to be judged by the investigator in charge of patient services
8. Women of childbearing age must obtain negative results from a pregnancy test, following the habitual procedures of each hospital at the beginning of inclusion in the study and commit to using a medically approved contraceptive throughout the whole period of the study

Participant type


Age group




Target number of participants


Participant exclusion criteria

1. Previous neoplastic history or haematological disease (Myeloproliferative disease, Myelodyplastic syndrome or Leukemia)
2. Patients with uncontrolled arterial hypertension (with arterial tension of more than 180/110 on more than one occasion)
3. Severe heart failure - New York Heart Association Class IV (NYHA IV)
4. Patients with malignant ventricular arrythmias or unstable angina
5. Diagnosis of Deep Vein Thrombosis (DVT) within the last 3 months
6. An active infection or wet gangrene on the day of bone marrow-mononuclear cells (BM-MNCs) infusion
7. Concomitant therapy which includes hyperbaric oxygen, vaso-active substances, agents against angiogenesis, cyclooxygenase-II (COX-II) inhibitors
8. Body mass index (BMI) of more than 40 Kg/m2
9. Patients diagnosed as alcoholics at the moment of inclusion
10. Proliferative retinopathy
11. A concomitant illness which reduces life expectancy to less than one year
12. Difficulty in treatment
13. Heart failure or ejection fraction (EF)< 30%
14. Cerebrovascular disease or Myocardial infarction in the last 3 months
15. Pregnant women or women of childbearing age who do not have an adequate method of contraception

Recruitment start date


Recruitment end date



Countries of recruitment


Trial participating centre

Servicio De Cirugia General

Sponsor information


Department of Health and National Health Service [Ministerio De Sanidad and Consejeria De Salud] (Spain)

Sponsor details

Hospital Universitario Virgen Del Rocio.
Fundacion Progreso Y Salud
Manuel Siurot S/N

Sponsor type

Hospital/treatment centre



Funder type

Hospital/treatment centre

Funder name

Department of Health (Ministerio De Sanidad) (Spain)

Alternative name(s)

Funding Body Type

Funding Body Subtype


Funder name

National Health Service (Consejeria De Salud De Andalucia) (Spain)

Alternative name(s)

Funding Body Type

Funding Body Subtype


Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Basic results (scientific)

Publication list

Publication citations

Additional files

Editorial Notes