Hepatic EncephalopathyEarly Phase 1NCT05279586
Secondary Prophylaxis of Hepatic Encephalopathy in Cirrhotic Patients
A Early Phase 1 study testing lactulose and colistin in people with Hepatic Encephalopathy, run by Madonna Magdy Fahmy.
Trial summary
The aim of this study is to compare the efficacy and safety of colistin versus lactulose for secondary prophylaxis of overt hepatic encephalopathy in patients with liver cirrhosis. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hepatic Encephalopathy
- What is being tested?
- lactulose and colistin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 316 participants
- Where
- No sites listed yet
- Study dates
- Mar 2022to Mar 2023
- Phase
- Early Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- • Age >18 years.
- Patients with liver cirrhosis and previous history of recovery from hepatic encephalopathy.
Who cannot join
- • History of taking lactulose in past 7 days
- Patients on secondary prophylaxis for spontaneous bacterial peritonitis
- Patients on psychoactive drugs, such as antidepressants or sedatives
- Previous transjugular intrahepatic portosystemic shunts or shunt surgery
- Significant comorbid illness such as heart, respiratory, or neurological disease such as Alzheimer's disease and Parkinson's disease
- Hepatocellular carcinoma or other neoplasias that could shorten life expectancy
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- Recent infection or antibiotic use within last 6 weeks
- Recent gastrointestinal bleeding in the past 6 weeks
- Renal insufficiency, myasthenia gravis.
- Hypersensitivity to colistin sulfate.
- Pregnancy or lactation
- Alcohol intake
Trial locations and contacts
No sites are listed yet.
About this study
Official title: Secondary Prophylaxis of Overt Hepatic Encephalopathy in Cirrhosis: a Randomized Controlled Trial of Colistin Versus Lactulose
The aim of this study is to compare the efficacy and safety of colistin versus lactulose for secondary prophylaxis of overt hepatic encephalopathy in patients with liver cirrhosis.
Read the detailed description
Hepatic encephalopathy (HE) is a reversible neuropsychiatric changes, it occurs in 30%-45% of cirrhotic patients during their life. Once HE is developed, the 1-year mortality exceeds 60%. The high morbidity and mortality combined with the costs underline the importance of effective treatment and prevention of HE.
The exact pathogenesis of HE is still unknown but ammonia is known to play a key role. Strategies to prevent and treat HE aims at reducing the production and absorption of gut derived neurotoxins, particularly ammonia, mainly through bowel cleansing, non absorbable disaccharides and non -absorbable antibiotics.
Patients with previous episode of overt HE, have a 40% cumulative risk of recurrence at 1 year. Because recurrent episodes of HE are associated with increased health care burden, poor prognosis, and risk of death, prevention of the recurrence of HE should be considered in each patient.
After an episode of overt HE has resolved, patients with cirrhosis should receive secondary prophylactic therapy for an indefinite period of time or until they undergo liver transplantation. Lactulose is considered the first line for secondary prophylaxis of overt HE while rifaximin is add-on therapy to lactulose.
Non-absorbable disaccharides like lactulose acts as both osmotic laxative, and gut acidifying agent reducing the production and the absorption of ammonia from the intestines by changing the gut microbiota. However, side effects of lactulose therapy including excessively sweet taste and gastrointestinal side effects such as abdominal pain, bloating, flatulence, severe and unpredictable diarrhea possibly leading to dehydration result in frequent non-adherence in clinical practice. Lactulose non-adherence, reported as a factor in 39% of hospital admissions, was the single most frequent precipitant of overt HE .
Rifaximin is a non-absorbable antibiotic with low systemic absorption, broad antimicrobial spectrum, and low frequency of side effects. It has a place in prevention of recurrence of HE when lactulose alone fails. However, the accessibility of rifaximin may be limited by its high cost.
Colistin sulfate is a polymyxin antibiotic which is active against aerobic gram-negative bacteria including most enterobacteria except Proteus. It is poorly absorbed from the gastrointestinal tract. Colistin sulfate being not systemically absorbed is used orally for bowel decontamination and treatment of intestinal infections.
Oral colistin is used for peri-operative selective decontamination of digestive tract in elective colorectal cancer patients in combination with tobramycin and amphotericin B. Also, combining oral colistin with ciprofloxacin has been effective in the prevention of Gram-negative sepsis in neutropenic patients without the emergence of significant resistance. However, no study up till now focuses on the use of oral colistin in the secondary prophylaxis of hepatic encephalopathy.
- Conditions
- Hepatic Encephalopathy
- Being tested
- lactulose, colistin
- Medical subject headings
- Hepatic Encephalopathy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
lactuloseDrug
Also called duphlac
all interventions are used in secondary prophylaxis in cirrhotic patients
colistinDrug
all interventions are used in secondary prophylaxis in cirrhotic patients
| Study group | Role | What they receive |
|---|---|---|
| patients that will receive lactulose | Active comparator | Cirrhotic patients who were recovered from HE will be randomized into lactulose group receiving 30-60 ml of lactulose orally in 2 or 3 divided doses so that patient passed 2-3 semisoft stools per day Receives: Drug: lactulose |
| patients that will receive colistin | Active comparator | colistin group receiving colistin sulfate 1.5 million I.U. tablet orally twice Receives: Drug: colistin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Development of overt hepatic encephalopathy
Number of Participants with Development of overt hepatic encephalopathy encephalopathy according to West Haven criteria
Measured: 6 months
Secondary outcomes (1)
Health related quality of life
HRQOL assessment using chronic liver disease questionnaire (higher score equates to worse quality of life)
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Mar 2022
- Study startMar 2022 (estimated)
- Primary completionFeb 2023 (estimated)
- Study completionMar 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hepatic EncephalopathyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 316 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Madonna Magdy Fahmy
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Madonna Magdy Fahmy, Tanta University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05279586
- Sponsor's protocol ID
- encephalopathy prophylaxis
- Status last verified
- Mar 2022
- First submitted
- 9 Feb 2022
- Last updated
- 15 Mar 2022
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Mar 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Secondary Prophylaxis of Overt Hepatic Encephalopathy in Cirrhosis: a Randomized Controlled Trial of Colistin Versus Lactulose
- ClinicalTrials.gov ID
- NCT05279586
- Acronym / sponsor ID
- encephalopathy prophylaxis
- Conditions
- Hepatic Encephalopathy
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 316 participants (estimated)
- Lead sponsor
- Madonna Magdy FahmyUniversity, hospital or other
- Study start
- Mar 2022 (estimated)
- Primary completion
- Feb 2023 (estimated)
- Study completion
- Mar 2023 (estimated)
- First posted
- 15 Mar 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The aim of this study is to compare the efficacy and safety of colistin versus lactulose for secondary prophylaxis of overt hepatic encephalopathy in patients with liver cirrhosis.
Detailed description
Hepatic encephalopathy (HE) is a reversible neuropsychiatric changes, it occurs in 30%-45% of cirrhotic patients during their life. Once HE is developed, the 1-year mortality exceeds 60%. The high morbidity and mortality combined with the costs underline the importance of effective treatment and prevention of HE.
The exact pathogenesis of HE is still unknown but ammonia is known to play a key role. Strategies to prevent and treat HE aims at reducing the production and absorption of gut derived neurotoxins, particularly ammonia, mainly through bowel cleansing, non absorbable disaccharides and non -absorbable antibiotics.
Patients with previous episode of overt HE, have a 40% cumulative risk of recurrence at 1 year. Because recurrent episodes of HE are associated with increased health care burden, poor prognosis, and risk of death, prevention of the recurrence of HE should be considered in each patient.
After an episode of overt HE has resolved, patients with cirrhosis should receive secondary prophylactic therapy for an indefinite period of time or until they undergo liver transplantation. Lactulose is considered the first line for secondary prophylaxis of overt HE while rifaximin is add-on therapy to lactulose.
Non-absorbable disaccharides like lactulose acts as both osmotic laxative, and gut acidifying agent reducing the production and the absorption of ammonia from the intestines by changing the gut microbiota. However, side effects of lactulose therapy including excessively sweet taste and gastrointestinal side effects such as abdominal pain, bloating, flatulence, severe and unpredictable diarrhea possibly leading to dehydration result in frequent non-adherence in clinical practice. Lactulose non-adherence, reported as a factor in 39% of hospital admissions, was the single most frequent precipitant of overt HE .
Rifaximin is a non-absorbable antibiotic with low systemic absorption, broad antimicrobial spectrum, and low frequency of side effects. It has a place in prevention of recurrence of HE when lactulose alone fails. However, the accessibility of rifaximin may be limited by its high cost.
Colistin sulfate is a polymyxin antibiotic which is active against aerobic gram-negative bacteria including most enterobacteria except Proteus. It is poorly absorbed from the gastrointestinal tract. Colistin sulfate being not systemically absorbed is used orally for bowel decontamination and treatment of intestinal infections.
Oral colistin is used for peri-operative selective decontamination of digestive tract in elective colorectal cancer patients in combination with tobramycin and amphotericin B. Also, combining oral colistin with ciprofloxacin has been effective in the prevention of Gram-negative sepsis in neutropenic patients without the emergence of significant resistance. However, no study up till now focuses on the use of oral colistin in the secondary prophylaxis of hepatic encephalopathy.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| patients that will receive lactulose | Active comparator | Drug: lactuloseCirrhotic patients who were recovered from HE will be randomized into lactulose group receiving 30-60 ml of lactulose orally in 2 or 3 divided doses so that patient passed 2-3 semisoft stools per day |
| patients that will receive colistin | Active comparator | Drug: colistincolistin group receiving colistin sulfate 1.5 million I.U. tablet orally twice |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- • Age >18 years.
Key exclusion criteria (12 listed)
- • History of taking lactulose in past 7 days
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| lactuloseAlso: duphlacall interventions are used in secondary prophylaxis in cirrhotic patients | Drug | patients that will receive lactulose |
| colistinall interventions are used in secondary prophylaxis in cirrhotic patients | Drug | patients that will receive colistin |
Primary outcome
Development of overt hepatic encephalopathy
Time frame: 6 months
Number of Participants with Development of overt hepatic encephalopathy encephalopathy according to West Haven criteria
1 secondary outcome
Health related quality of life
Time frame: 6 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Mar 2022.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing lactulose and colistin in people with Hepatic Encephalopathy, run by Madonna Magdy Fahmy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 15 Mar 2022. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Madonna Magdy Fahmy, Master (01099794496, madona.magdy@med.tanta.edu.eg), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Development of overt hepatic encephalopathy (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Mar 2022.