Ursodeoxycholic Acid And Cholestasis Of Pregnancy (CERTO)

Intrahepatic Cholestasis Of Pregnancy: Clinical Impact Of Ursodeoxycholic Acid Treatment

The study is a multicenter randomized double blind placebo controlled trial. The study will be conducted on pregnant women with a diagnosis of intrahepatic cholestasis of pregnancy (ICP) in third level hospitals (that are also Academic Hospitals).

Pregnant women at the time of ICP diagnosis will be randomized in two groups:

Group 1 - will receive placebo and obstetrical monitoring until delivery Group 2 - will receive UDCA at the dose of 20 mg/Kg/day and obstetrical monitoring until delivery.

The hypotheses are that UDCA treatment will be superior to placebo and effective in:

reducing the rate of prematurity; improving maternal biochemical parameters and symptoms.

Study Overview

• Status: Withdrawn
• Conditions: Intrahepatic Cholestasis of Pregnancy
• Intervention / Treatment: Drug: Placebo; Drug: Ursodeoxycholic Acid

• Study Type: Interventional
• Phase: Phase 3

Contacts and Locations

Study Locations

• Italy
  • Bologna, Italy, 40138
    • S.Orsola-Malpighi Hospital
  • Bologna, Italy, 40100
    • UOC Ostetricia e Ginecologia, Ospedale Maggiore
  • Modena, Italy
    • Gastroenterology and Liver Clinic, Azienda Ospedaliero-Universitaria, University of Modena and Reggio Emilia
  • Padua, Italy, 34100
    • Dept. of Surgical and Gastroenterological Sciences, University of Padova
  • Palermo, Italy
    • Gastroenterology Unit, Policlinic of Palermo
  • Rome, Italy, 00168
    • Internal Medicine Department, Gemelli Hospital, Catholic University of Sacred Heart
  • Foggia
    • San Giovanni Rotondo, Foggia, Italy, 71013
      • Divisione di Gastroenterologia, IRCCS Casa Sollievo della Sofferenza

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Pregnant state (after week 20 of gestation)
• Total Serum BA elevation (>10 micromol/l)
• Transaminases elevation (ALT>40 UI/L and AST>37 UI/L)
• Occurrence of pruritus
• Informed consent signed

Exclusion Criteria:

• Infectious diseases (HBV, HDV, HCV related liver disease, EBV, CMV, HIV infection)
• Dermatologic diseases
• Metabolic diseases (including alcohol abuse)
• Other causes of cholestasis (i.e. PBC; PSC)
• Autoimmune liver disease
• Obstructive biliary diseases
• Drug related pathologies
• Known or suspected hyper-sensibility to the drug or the pharmacological class under study
• Serious clinical conditions that, according to the judgment of the investigator, contraindicate the participation to the study (heart, kidney and liver disease)
• Use of cholestyramine
• Patients not able or not willing to follow the procedures of the protocol
• Patients not signing the informed consent
• Onset of ICP during of after the 36th week of pregnancy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; obstetrical monitoring plus placebo	Drug: Placebo; 300 mg capsules 20 mg/kg body weight/day divided in three administrations per day from enrolment until delivery
Experimental: Ursodeoxycholic acid; obstetrical monitoring plus active drug	Drug: Ursodeoxycholic Acid; 300 mg capsules 20 mg/kg body weight/day divided in three administrations per day from enrolment until delivery

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of participants with preterm delivery (before week 37)	at the time of delivery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pruritus on the Visual Analogue Scale		from enrollment until delivery
Transaminases		from enrolment until delivery
Bile Acids		from enrolment until delivery
Fetal movement count	mother evaluation	from enrolment until delivery
Number of pregnancies with cardiotocography suggestive of fetal stress		from enrolment until delivery
APGAR index		1 and 5 minutes after birth
Number of pregnancies with Green stained amniotic fluid	obstetrician evaluation	at delivery

Collaborators and Investigators

• Sponsor: University of Bologna
• Investigators: Study Director: Giuseppe Mazzella, Professor, University of Bologna; Principal Investigator: Francesco Azzaroli, Professor, University of Bologna

Publications and helpful links

General Publications

• Walker KF, Chappell LC, Hague WM, Middleton P, Thornton JG. Pharmacological interventions for treating intrahepatic cholestasis of pregnancy. Cochrane Database Syst Rev. 2020 Jul 27;7(7):CD000493. doi: 10.1002/14651858.CD000493.pub3.

Study record dates

Study Major Dates

• Study Start: November 1, 2010
• Primary Completion (Anticipated): November 1, 2013
• Study Completion (Anticipated): November 1, 2013

Study Registration Dates

• First Submitted: October 19, 2010
• First Submitted That Met QC Criteria: October 21, 2010
• First Posted (Estimate): October 22, 2010

Study Record Updates

• Last Update Posted (Estimate): May 12, 2016
• Last Update Submitted That Met QC Criteria: May 10, 2016
• Last Verified: May 1, 2016

More Information

Terms related to this study

• Keywords: pregnancy; ursodeoxycholic acid; ICP; cholestasis
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Biliary Tract Diseases; Bile Duct Diseases; Pregnancy Complications; Cholestasis; Cholestasis, Intrahepatic; Gastrointestinal Agents; Cholagogues and Choleretics; Ursodeoxycholic Acid
• Other Study ID Numbers: CERTO