Clinical Trial Details
— Status: Not yet recruiting
Administrative data
| NCT number |
NCT05279586 |
| Other study ID # |
encephalopathy prophylaxis |
| Secondary ID |
|
| Status |
Not yet recruiting |
| Phase |
Early Phase 1
|
| First received |
|
| Last updated |
|
| Start date |
March 2022 |
| Est. completion date |
March 2023 |
Study information
| Verified date |
March 2022 |
| Source |
Tanta University |
| Contact |
Madonna Magdy Fahmy, Master |
| Phone |
01099794496 |
| Email |
madona.magdy[@]med.tanta.edu.eg |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical 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.
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.
