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]

• Sponsor: Abbott (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02377947
• Collaborator: (none)
• Enrollment: 50
• Locations: 3
• Duration (Months): 3
• Patients Per Site: 16.7
• Patients Per Site Per Month: 5.6

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
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 Design

• Study Type: Observational
• Actual Enrollment: 50 participants
• Observational Model: Other
• Time Perspective: Other
• Official Title: 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]
• Study Start Date: Dec 1, 2015
• Actual Primary Completion Date: Mar 1, 2016
• Actual Study Completion Date: Mar 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
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

Outcome Measures

Primary Outcome Measures

1. Complete Reversal [24 hrs]

   Percentage of patients with complete reversal of deep-grade (Grade 3 and 4 West-Haven Criteria) Hepatic Encephalopathy after administration of lactulose retention enema

2. Complete Reversal [48 hrs]

   Percentage of patients with complete reversal of deep-grade (Grade 3 and 4 West-Haven Criteria) Hepatic Encephalopathy after administration of lactulose retention enema

Secondary Outcome Measures

1. Hepatic Encephalopathy (HE) Grade Shift at 24 and 48 Hours [HE Grade shift at 24 hrs and HE Grade shift at 48 hrs]

   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

2. Time to Complete Reversal [up to 48 hrs]

   Time to complete reversal of deep-grade (Grade 3 and 4 West-Haven Criteria) HE after administration of lactulose retention enema

3. Mortality [within 48 hrs]

   Mortality in patients treated with lactulose retention enema

Other Outcome Measures

1. Safety of Lactulose Retention Enema (Number of Adverse Drug Reactions & Complications). [Chart Review of Events over 48 Hour Period]

   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.

2. Reduction in Blood Ammonia Level [reported at 48 hrs]

   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

3. Duration of Hospital Stay [upto 30 days of hospital admission]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Medanta Hospital	Gurgaon		India	122001
2	Research facility ORG-000333	Gurgaon		India	122001
3	Sir Ganga Ram Hospital	New Delhi		India	110060

Sponsors and Collaborators

• Abbott

Investigators

• Study Chair: Dyotona Roy-Sengupta, Abbott

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Abbott
• ClinicalTrials.gov Identifier: NCT02377947
• Other Study ID Numbers: EPIDJ001; REF/2014/11/007981
• First Posted: Mar 4, 2015
• Last Update Posted: Feb 10, 2020
• Last Verified: Feb 1, 2020

• Keywords provided by Abbott: Lactulose Retention Enema; Hepatic Encephalopathy, Grade 3 or 4 West Haven Criteria; The Retro Study
• Additional relevant MeSH terms: Hepatic Encephalopathy; Brain Diseases

Study Results

Participant Flow

Arm/Group Title	Patients With Cirrhosis (Grade 3 & 4 Per West Haven cr.)
Arm/Group Description	Patients with cirrhosis having grade 3 or grade 4 (West Haven Criteria) hepatic encephalopathy who were treated with Lactulose retention enema
Period Title: Overall Study
STARTED	50
COMPLETED	50
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Patients With Cirrhosis (Grade 3 & 4 Per West Haven cr.)
Arm/Group Description	Patients with cirrhosis having grade 3 or grade 4 (West Haven Criteria) hepatic encephalopathy who were treated with Lactulose retention enema
Overall Participants	50
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	50 100%
>=65 years	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	48.38 (10.18)
Sex: Female, Male (Count of Participants)
Female	10 20%
Male	40 80%
Region of Enrollment (Count of Participants)
India	50 100%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Patients With Cirrhosis (Grade 3 & 4 Per West Haven cr.)
Arm/Group Description	Patients with cirrhosis having grade 3 or grade 4 (West Haven Criteria) hepatic encephalopathy who were treated with Lactulose retention enema
Measure Participants	50
Number (95% Confidence Interval) [percentage of participants]	80 160%

2. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Patients With Cirrhosis (Grade 3 & 4 Per West Haven cr.)
Arm/Group Description	Patients with cirrhosis having grade 3 or grade 4 (West Haven Criteria) hepatic encephalopathy who were treated with Lactulose retention enema
Measure Participants	50
Number (95% Confidence Interval) [percentage of participants]	90 180%

3. Secondary Outcome

Title	Hepatic Encephalopathy (HE) Grade Shift at 24 and 48 Hours
Description	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
Time Frame	HE Grade shift at 24 hrs and HE Grade shift at 48 hrs

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Patients With Cirrhosis (Grade 3 & 4 Per West Haven cr.)
Arm/Group Description	Patients with cirrhosis having grade 3 or grade 4 (West Haven Criteria) hepatic encephalopathy who were treated with Lactulose retention enema
Measure Participants	50
shift from HE Grade 3 to <2 after 24 hours	86.67 173.3%
shift from HE Grade 4 to <2 after 24 hours	20.0 40%
shift from HE Grade 3 to <2 after 48 hours	95.56 191.1%
shift from HE Grade 4 to <2 after 48 hours	40.0 80%

4. Secondary Outcome

Title	Time to Complete Reversal
Description	Time to complete reversal of deep-grade (Grade 3 and 4 West-Haven Criteria) HE after administration of lactulose retention enema
Time Frame	up to 48 hrs

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Patients With Cirrhosis (Grade 3 & 4 Per West Haven cr.)
Arm/Group Description	Patients with cirrhosis having grade 3 or grade 4 (West Haven Criteria) hepatic encephalopathy who were treated with Lactulose retention enema
Measure Participants	50
Mean (Standard Deviation) [Hours]	25.39 (8.85)

5. Secondary Outcome

Title	Mortality
Description	Mortality in patients treated with lactulose retention enema
Time Frame	within 48 hrs

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Patients With Cirrhosis (Grade 3 & 4 Per West Haven cr.)
Arm/Group Description	Patients with cirrhosis having grade 3 or grade 4 (West Haven Criteria) hepatic encephalopathy who were treated with Lactulose retention enema
Measure Participants	50
Count of Participants [Participants]	0 0%

6. Other Pre-specified Outcome

Title	Safety of Lactulose Retention Enema (Number of Adverse Drug Reactions & Complications).
Description	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.
Time Frame	Chart Review of Events over 48 Hour Period

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Patients With Cirrhosis (Grade 3 & 4 Per West Haven cr.)
Arm/Group Description	Patients with cirrhosis having grade 3 or grade 4 (West Haven Criteria) hepatic encephalopathy who were treated with Lactulose retention enema
Measure Participants	50
Number [number of events]	5

7. Other Pre-specified Outcome

Title	Reduction in Blood Ammonia Level
Description	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
Time Frame	reported at 48 hrs

Outcome Measure Data

Analysis Population Description

The ammonia levels were available at baseline for 28 patients where as the last observed blood ammonia level after administration of lactulose enema was available for 4 patients. Thus the change from baseline was calculated for 4 patients. The Change value = Visit value - Baseline Value

Arm/Group Title	Patients With Cirrhosis (Grade 3 & 4 Per West Haven cr.)
Arm/Group Description	Patients with cirrhosis having grade 3 or grade 4 (West Haven Criteria) hepatic encephalopathy who were treated with Lactulose retention enema
Measure Participants	4
Mean (Standard Deviation) [Mcg/DL]	-70.6 (11.32)

8. Other Pre-specified Outcome

Title	Duration of Hospital Stay
Time Frame	upto 30 days of hospital admission

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Patients With Cirrhosis (Grade 3 & 4 Per West Haven cr.)
Arm/Group Description	Patients with cirrhosis having grade 3 or grade 4 (West Haven Criteria) hepatic encephalopathy who were treated with Lactulose retention enema
Measure Participants	50
Mean (Standard Deviation) [hours]	229.4 (147.64)

Adverse Events

Adverse Event Reporting Description	As this study was a retrospective chart review of 50 patients who were treated with lactulose enema, only (S)ADRs and complications were collected. Thus, the total of participants at risk were 50 for ADRs and 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.
Arm/Group Title	Patients With Cirrhosis (Grade 3 & 4 Per West Haven cr.)
Arm/Group Description	Patients with cirrhosis having grade 3 or grade 4 (West Haven Criteria) hepatic encephalopathy who were treated with Lactulose retention enema
All Cause Mortality
	Patients With Cirrhosis (Grade 3 & 4 Per West Haven cr.)
	Affected / at Risk (%)	# Events
Total	6/50 (12%)
Serious Adverse Events
	Patients With Cirrhosis (Grade 3 & 4 Per West Haven cr.)
	Affected / at Risk (%)	# Events
Total	0/50 (0%)
Other (Not Including Serious) Adverse Events
	Patients With Cirrhosis (Grade 3 & 4 Per West Haven cr.)
	Affected / at Risk (%)	# Events
Total	3/50 (6%)
Gastrointestinal disorders
Diarrhea and Abdominal discomfort	1/50 (2%)	2
Abdominal fullness and discomfort	1/50 (2%)	2
Injury, poisoning and procedural complications
Mild rectal bleed	1/50 (2%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.