A Retrospective, Open-label, Uncontrolled Cohort Study to Assess the Effectiveness and Safety of Lactulose Retention Enema in the Treatment of Cirrhotic Patients With Grade 3 or 4 (West Haven Criteria) Hepatic Encephalopathy (HE) [The RETRO Study]

This is a retrospective study in adult patients with cirrhosis and grade 3 or 4 HE (West Haven Criteria) to evaluate the effectiveness and safety of lactulose retention enema in the treatment of deep grade HE (West Haven Criteria). The study will be conducted retrospectively in a multi center of a multispecialty tertiary care hospital in India, in which lactulose retention enema is the mainstay of management of cirrhotic patients with grade 3 or 4 HE (West Haven criteria). Dosing of lactulose retention enema in this study will be done according to the dosing described for rectal administration of lactulose (India): 300ml of lactulose mixed with 700ml of potable water to be used as a retention enema; the enema is to be retained for 30-60 minutes and repeated every 4-6 hours until the patient is able to take oral medication. This treatment regime is also the standard protocol of management of deep grade HE (West Haven criteria) in the study centers. The standard treatment protocol of deep grade HE (West Haven criteria) of the study centers will also ensure that all known contraindications of lactulose will be respected before administration of lactulose retention enema to the study patients. The retrospective hospital records of the patient population of interest within the past 6 months will be identified, and these records will be used to collect data required for analysis.

Study Overview

• Status: Completed
• Conditions: Hepatic Encephalopathy

Detailed Description

Data to be collected:

Data that would be collected for the study as part of retrospective chart review:

1. Patient demographics: age, gender, weight
2. Medical history
3. Etiology of cirrhosis (alcohol abuse, hepatitis, autoimmune, cryptogenic, other)
4. Diagnosis of cirrhosis
5. History of previous HE (if yes, the number of episodes in the past)
6. Grade of HE (as per the West-Haven criteria) at admission, 24 hrs and 48 hours post treatment with lactulose
7. Precipitating factor(s) of HE (Dehydration, GI bleeding, protein overload, constipation, infection, others)
8. Dose and duration of lactulose enema
9. Treatment given for precipitating factors
10. Laboratory data on haemoglobin, platelet, bilirubin, albumin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), urea, creatinine, sodium, potassium, and blood ammonia
11. Complete reversal of deep-grade HE (< Grade 2 as per West-Haven criteria) (yes/no)
12. Time to complete reversal of deep-grade HE
13. Number of days in hospital
14. Adverse drug reaction experienced by the patient
15. Complications experienced by the patient
16. Other pharmacovigilance relevant information (OPRI)

• Study Type: Observational
• Enrollment (Actual): 50

Contacts and Locations

Study Locations

• India
  • Gurgaon, India, 122001
    • Medanta Hospital
  • Gurgaon, India, 122001
    • Research facility ORG-000333
  • New Delhi, India, 110060
    • Sir Ganga Ram Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 63 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Retrospective study - data charts of the cirrhotic patients having grade III and IV and who were administered lactulose enema will be reviewed.

Description

Inclusion Criteria:

• Patients aged between 18 and 65 years of either gender.
• Patients admitted to the hospital with liver cirrhosis and grade 3 or grade 4 (West Haven Criteria) HE
• Patients treated with lactulose retention enema within 48 hours of onset of grade 3 or 4 (West Haven Criteria) HE

Exclusion Criteria:

• Patients treated with agents other than lactulose retention enema for grade 3 or 4 (West Haven Criteria) HE.
• Patients who had significant concomitant diseases that could impair or contribute to the impairment of consciousness
• Patients who had a major neuropsychiatric illness
• Patients who had a contraindication to lactulose, including Hypersensitivity to the active substance or to any of the ingredients; Galactosaemia; Gastrointestinal obstruction, digestive perforation or risk of digestive perforation

Study Plan

How is the study designed?

Design Details

• Observational Models: Other
• Time Perspectives: Other

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Patients with cirrhosis (grade 3 & 4 per west haven cr.); Patients with cirrhosis having grade 3 or grade 4 (West Haven Criteria) hepatic encephalopathy who were treated with Lactulose retention enema

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete Reversal	Percentage of patients with complete reversal of deep-grade (Grade 3 and 4 West-Haven Criteria) Hepatic Encephalopathy after administration of lactulose retention enema	24 hrs
Complete Reversal	Percentage of patients with complete reversal of deep-grade (Grade 3 and 4 West-Haven Criteria) Hepatic Encephalopathy after administration of lactulose retention enema	48 hrs

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hepatic Encephalopathy (HE) Grade Shift at 24 and 48 Hours	Grade shift at 24 and 48 hours - from baseline to 24 and 48 hours post administration of lactulose retention enema. Complete reversal of deep grade HE is defined as subjects having HE grade=<grade 2 as per West-Haven criteria where grade 0 is Normal, Grade 1 is Mild lack of awareness, Grade 2 is Lethargic, Grade 3 is Somnolent but arousable and Grade 4 is Coma	HE Grade shift at 24 hrs and HE Grade shift at 48 hrs
Time to Complete Reversal	Time to complete reversal of deep-grade (Grade 3 and 4 West-Haven Criteria) HE after administration of lactulose retention enema	up to 48 hrs
Mortality	Mortality in patients treated with lactulose retention enema	within 48 hrs

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety of Lactulose Retention Enema (Number of Adverse Drug Reactions & Complications).	Safety of Lactulose retention enema (number of adverse drug reactions & complications). Complications pertinent to lactulose retention enema are in reference to potential adverse effects associated with the use of rectal device associated with the application of the lactulose retention enema kit.	Chart Review of Events over 48 Hour Period
Reduction in Blood Ammonia Level	Change from baseline was calculated at the end of treatment by using following formula wherever applicable: Change from baseline = Blood ammonia level at the end of treatment - Blood ammonia level at baseline	reported at 48 hrs
Duration of Hospital Stay		upto 30 days of hospital admission

Collaborators and Investigators

• Sponsor: Abbott
• Investigators: Study Chair: Dyotona Roy-Sengupta, Abbott

Study record dates

Study Major Dates

• Study Start: December 1, 2015
• Primary Completion (Actual): March 1, 2016
• Study Completion (Actual): March 1, 2016

Study Registration Dates

• First Submitted: February 17, 2015
• First Submitted That Met QC Criteria: February 26, 2015
• First Posted (Estimate): March 4, 2015

Study Record Updates

• Last Update Posted (Actual): February 10, 2020
• Last Update Submitted That Met QC Criteria: February 6, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Keywords: Lactulose Retention Enema; Hepatic Encephalopathy, Grade 3 or 4 West Haven Criteria; The Retro Study
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Failure; Hepatic Insufficiency; Metabolic Diseases; Central Nervous System Diseases; Nervous System Diseases; Liver Diseases; Brain Diseases, Metabolic; Hepatic Encephalopathy; Brain Diseases
• Other Study ID Numbers: EPIDJ001; REF/2014/11/007981 (Registry Identifier: Clinical Trial registry of India)