The Impact of Carvedilol Posology on Clinically Significant Portal Hypertension: Insights From Elastography Measurements
Phase: NA
Conditions: Clinically Significant Portal Hypertension
Sponsor: Centro Hospitalar De São João, E.P.E.

 
1 
 
 
 
Centro Hospitalar Trás-os-Montes e Alto Douro 
 
 
 
 
 
 
 
 
 
 
 
 
RESEARCH PROTOCOL 
 
 
The impact of carvedilol posology on Clinically Significant Portal 
Hypertension: Insights from Elastography Measurements 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
31 May 2023 

 
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Title: The impact of carvedilol posology on Clinically Significant Portal Hypertension: 
Insights from Elastography Measurements 
Name: Bruno Daniel dos Santos Besteiro 
Phone Number: +351919818533 
E-mail: u014986@chsj.min-saude.pt 
 
Authors: Bruno Besteiro1,2, Manuel Marques da Cruz3,4, Cláudia Alves5, Fátima Costa6, 
Mariana Nunes7, Ana Barreira8, Joana Calvão8, Mónica Mesquita8, Sónia Carvalho8, Inês 
Pinho8 Paulo Carrola8, José Presa Ramos8 
 
Authors Affiliation 
1- Internal Medicine Department, Centro Hospitalar e Universitário de São João - 
Oporto (Portugal)  
2- Faculty of Medicine, Oporto University, Centro Hospitalar e Universitário de São João, 
Oporto, Portugal  
3- Unidade de Saúde Pública do Agrupamento de Centros de Saúde Marão e Douro 
Norte, ARS Norte, Vila Real 
4- Faculty of Medicine University of Porto, MEDCIDS and CINTESIS, Porto, Portugal 
5- Internal Medicine Department, Hospital Distrital de Santarém – Santarém, Portugal  
6- Internal Medicine Department, Centro Hospitalar do Tâmega e Sousa – Penafiel, Portugal 
7- Internal Medicine Department, Centro Hospitalar de Trás os Montes e Alto Douro Vila Real, 
Portugal 
8- Liver Unit, Internal Medicine Department, Centro Hospitalar de Trás-os-Montes e Alto Douro 
- Vila Real, Portugal 
 
 
Unit:  Liver Unit, Internal Medicine Department, Centro Hospitalar de Trás-os-Montes e Alto 
Douro - Vila Real, Portugal 
 
Introduction / Theoretical foundations: 
Transitory elastography is a non-invasive diagnostic method that has been used for the 
diagnosis and follow-up of patients with clinically significant portal hypertension (CSPH). In 
this context, the use of targeted therapies to reduce complications resulting from this finding 
plays a crucial role in managing these patients. 
Carvedilol is a non-selective beta-blocker currently considered the first-line drug for treating 
patients with CSPH. Regarding its pharmacokinetic characteristics, its half-life is 
approximately 7 to 10 hours. However, there is still a debate in dosing regimen, specially 
regarding dose interval, with a potential lower bioavalability in once daily regimens 
Nevertheless, although the dosing frequency may influence portal pressure and cardiac 
function, the direct impact on the value of splenic and liver elastography is not fully 
understood, and there are no studies directly comparing and evalutiang this topic. Therefore, 
focused studies assessing the impacto f once-daily vs twice daily dosing regimens become 
essential to improving clinical practice. 
 
 

 
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Objectives:  To assess the acute eﬀects of carvedilol posology in pajents with clinically 
signiﬁcant portal hypertension (CSPH), as a surrogate marker of bioavailability. 
 
Study design: experimental study including pajents with CSPH considered responders to 
carvedilol prescribed twice daily. These pajents had their spleen sjﬀness measurement 
(SSM) and liver sjﬀness measurement (LSM) measured through elastography aler 
suspending their second daily carvedilol intake. Results from the SSM were compared with 
the values measured while under treatment and before being prescribed with carvedilol. 
Addijonally, comparisons for under treatment with carvedilol and 24-hour suspension were 
strajﬁed according to carvedilol daily dosage, D’Amico classiﬁcajon, the Model for End-stage 
Liver Disease (MELD) scores, Child-Pugh score, and aejologies for portal hypertension. The 
same procedure was repeated for the results of LSM.  
 
Target population:  pajents with CSPH considered responders to carvedilol prescribed twice 
daily 
 
Inclusion and exclusion criteria:  
 
Inclusion criteria 
• 
Patients with CSPH (deﬁned as a LSM ³ 25 kPa or SSM over 45kPa prior to introducjon 
of carvedilol) 
Exclusion criteria 
• 
Non-responders to NSBB (deﬁned as a reducjon of their SSM of less than 10% 
• 
Pajents under treatment with any NSBB other than carvedilol  
• 
Patients with a dosing regimen other than twice daily 
• 
Pajents with contraindicajons to NSBB use 
• 
Pajents who had not been performed a SSM or LSM through TE while under 
treatment within 3 months prior to the beginning of the study 
• 
Obesity (deﬁned as body mass index (BMI) > 30 m/kg2) 
• 
Pajents with portal venous thrombosis  
• 
Pajents who refused to parjcipate in the study 
 
Recruitment and Selection Process of Participants: Pajents admiqed to the Liver Unit aler 
meejng the inclusion and exclusion criteria, provided that they agree to parjcipate aler 
being adequately informed about the study. 
 
Variables: gender, age, aejologies for CSPH, D’Amico classiﬁcajon, the Model for End-stage 
Liver Disease (MELD) scores (both MELD-Na, and MELD 3.0), Child-Pugh score, and carvedilol 
daily dosage  
 
Potential benefits/risks of the study:  To assess if twice a day prescripjon may be beqer in 
keeping bioavailability of carvedilol and the intended eﬀects of the treatment for CSPH 
throughout the day. 
 
Confidentiality and Anonymity: Throughout the research development and presentation of 
results, confidentiality and anonymity of the participants are ensured. When transferring 
clinical data to the database, each participant will be assigned a code number that allows for 

 
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the decoding of their identity. The code will only be accessible to the researchers and will be 
stored separately from the main database. Access to the computer containing the 
aforementioned information will be restricted, requiring a specific username and password 
for each investigator. 
 
Dissemination of Results: The intention is to publish the work in a national/international 
scientific journal 
 
Duration of the research study: This is a study that will take place over a period of 1 month. 
  
Ethical considerations: The present study will be approved by the ethics committees of each 
center and will follow the guidelines of Good Clinical Practice, the Declaration of Helsinki, and 
local laws, as well as the Regulation of the European Parliament and of the Council (EU) 
2016/679 on the protection of individuals with regard to the processing of personal data, 
which was enacted on April 27, 2016. 
 
Direct and indirect costs for CHTMAD and other participating centers: None 
 
Funding and insurance:  None 
 
References 
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Renewing consensus in portal hypertension. J Hepatol. 2022 Apr;76(4):959-974. 
 
2. Reiberger T, Ulbrich G, Ferlitsch A, Payer BA, Schwabl P, Pinter M, Heinisch BB, Trauner M, 
Kramer L, Peck-Radosavljevic M; Vienna Hepatic Hemodynamic Lab. Carvedilol for primary 
prophylaxis of variceal bleeding in cirrhotic patients with haemodynamic non-response to 
propranolol. Gut. 2013 Nov;62(11):1634-41. 
 
3. Reiberger T. The Value of Liver and Spleen Stiffness for Evaluation of Portal Hypertension in 
Compensated Cirrhosis. Hepatol Commun. 2022 May;6(5):950-964.