Upper Gastrointestinal HemorrhagePhase 4NCT05624229
Efficacy of Proton Pump Inhibitors in Cirrhotic Patients With Acute Variceal Bleeding
A Phase 4 study testing Proton Pump Inhibitors and No Proton Pump Inhibitors in people with Upper Gastrointestinal Hemorrhage, run by West China Hospital.
Trial summary
Acute Variceal Bleeding (AVB) in patients with liver cirrhosis is a common clinical critical disease. There is little evidence for the effect of proton pump inhibitor (PPI) use in patients with AVB, and there is no study on the efficacy of PPI combined with standard therapy in patients with AVB. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Upper Gastrointestinal Hemorrhage
- What is being tested?
- Proton Pump Inhibitors and No Proton Pump Inhibitors
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 672 participants
- Where
- No sites listed yet
- Study dates
- 1 Oct 2023to 31 Dec 2028
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
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 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Liver cirrhosis.
- The etiology of portal hypertension is cirrhosis.
- Patients presenting with acute esophageal variceal bleeding proven by emergency endoscopy within 24 hours.
- Be willing to participate in this clinical study, comply with the study requirements and sign the informed consent
Who cannot join
- non-cirrhotic portal hypertension
- the time from admission to endoscopy was more than 24 hours
- patients with peptic ulcer or gastroesophageal reflux disease requiring PPI therapy
- PPI use for more than 2 weeks before admission
- received endoscopic or interventional therapy within the previous 4 weeks
- PPI allergy
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- Chronic renal insufficiency (CKD stage 3-5)
- Severe cardiopulmonary dysfunction (such as heart failure grade 3-4, respiratory failure, etc.)
- Hepatocellular carcinoma (Barcelona Clinic Liver Cancer (BCLC) stage C and D)
- other advanced malignancies (life expectancy less than 6 months)
- Pregnancy
About this study
Acute Variceal Bleeding (AVB) in patients with liver cirrhosis is a common clinical critical disease. There is little evidence for the effect of proton pump inhibitor (PPI) use in patients with AVB, and there is no study on the efficacy of PPI combined with standard therapy in patients with AVB.
Read the detailed description
AVB in patients with liver cirrhosis is a common clinical critical disease, with a 6-week mortality rate as high as 20%. Currently, many guidelines recommend the use of vasoactive drugs (terlipressin, somatostatin or octreotide) combined with endoscopic therapy (Endoscopic Variceal Ligation (EVL), endoscopic injection sclerotherapy (EIS) and the use of prophylactic antibiotics for patients with AVB.
PPI is a commonly used antacid agent, which has a significant antacid effect, protects the gastrointestinal mucosa, promotes blood coagulation, healing ulcers, effectively stops bleeding and prevents rebleeding. There is a consensus that PPI should be used before and after endoscopic therapy in patients with non-variceal acute bleeding. However, studies on the efficacy of PPI after EVL are still limited and lack of sufficient convincing. In a randomized controlled study, pantoprazole treatment was found to be associated with significantly smaller ulcers 10 days after elective EVL in secondary prevention patients with cirrhosis. Another randomized controlled study in 2013 found that patients with cirrhosis and AVB treated with PPI for 19 days after endoscopic hemostasis had smaller ulcers and fewer overall side-effects, but there was no statistically significant difference in rate of 5-day treatment failure, 6-week rebleeding rate and 6-week mortality. In 2017, a study included 637 patients with acute bleeding from liver cirrhosis, 80% of whom were treated with acid suppression therapy, and the study found that acid suppression therapy had no significant effect on long-term bleeding rate and mortality. However, negative effects of PPI have been reported in patients with cirrhosis, such as spontaneous bacterial peritonitis and hepatic encephalopathy. It is found that patients with cirrhosis and ascites had an increased risk of first hepatic encephalopathy with PPI use, and also found that patients with cirrhosis had an increased risk of hepatic encephalopathy and death with PPI use. Therefore, PPI use in patients with cirrhosis should be more cautious. However, the duration of PPI use in these studies was long, and there are no data to clarify the effect of short-term PPI use.
At present, there is no consensus among the major guidelines on the use of PPI in patients with acute AVB in liver cirrhosis, and the UK guidelines do not recommend the use of PPI unless accompanied by gastrointestinal ulcer. The use of PPI was not mentioned in the guidelines of the American Endoscopic Society and the European Endoscopic Society. The 2021 Baveno 7 guideline clearly proposes that PPI should be stopped immediately once AVB is identified as cirrhosis. The latest meta-analysis in 2022 showed that the use of PPI before endoscopy may reduce the need for endoscopic hemostasis in patients with upper gastrointestinal tract, but there was no sufficient evidence to confirm the effect on clinical outcomes including 30-day mortality and rebleeding. It can be concluded that there is no consensus on the use of PPI in patients with AVB in cirrhosis, and the recommendations of guidelines lack high-quality studies to improve the convincing.
In summary, there is little evidence for the effect of PPI use in patients with AVB in liver cirrhosis, and there is no study on the efficacy of PPI combined with endoscopic therapy in patients with AVB in liver cirrhosis. Therefore, the investigators planned to design a multicenter prospective randomized controlled trial to explore the efficacy of PPI in cirrhotic patients with AVB. In this study, the following questions were investigated: 1. Can PPI reduce the 5-day treatment failure rate in cirrhotic patients with AVB; 2. Can it reduce the 6-week rebleeding rate, mortality, and complications in patients with liver cirrhosis and AVB.
- Conditions
- Upper Gastrointestinal Hemorrhage
- Being tested
- Proton Pump Inhibitors, No Proton Pump Inhibitors
- Keywords
- Proton Pump Inhibitors, Acute Variceal Bleeding, Liver Cirrhosis, Endoscopic Variceal Ligation
- Medical subject headings
- Gastrointestinal Hemorrhage, Liver Cirrhosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Proton Pump InhibitorsDrug
Also called Drug: Omeprazole, Drug: Esomeprazole, Drug: Rabeprazole, Drug: Pantoprazole
PPI infusion continued to use for 5 days in experimental group
No Proton Pump InhibitorsDrug
PPI infusion stopped in standard group after endoscopy.
| Study group | Role | What they receive |
|---|---|---|
| Standard group | Placebo comparator | Early treatment is mainly aimed at correcting hypovolemic shock, preventing gastrointestinal bleeding-related complications, effective control of bleeding, monitoring vital signs and urine output.
Medical treatment included initiation and maintenance of vasoactive agents as soon as possible for 2 to 5 days, and prophylactic antibiotics (preferably ceftriaxone sodium or quinolones) by intravenous infusion for 5 days.
Endoscopic intervention was performed within 12 hours after presentation and generally no longer than 24 hours. PPI was stopped immediately after endoscopic treatment.
Early TIPS is determined according to the technology and concept of each unit. Receives: Drug: No Proton Pump Inhibitors |
| Standard group+PPI | Experimental | PPI continued after endoscopic treatment for 5 days. Receives: Drug: Proton Pump Inhibitors |
What is being measured
The primary outcome is the main question the study is designed to answer.
5-day treatment failure rate
Failure of initial hemostasis Initial hemostasis was defined as not achieving a 24h bleeding-free period within the first 48h after treatment together with stable vital signs based on Baveno consensus criteria.
UGI bleeding occurred after initial hemostasis and within 5 days after enrollment was defined as early rebleeding. UGI bleeding was proven to be from esophageal varices.
Measured: 5 days
Secondary outcomes (4)
Rebleeding rate within 42 days
Rebleeding rate within 42 days
Measured: 42 days
Mortality rate within 42 days
Mortality rate within 42 days
Measured: 42 days
Rescure treatment
Number of participants who need of TIPs, re-endoscopy, surgery, etc
Measured: 42 days
Compilcations
Occurrence of chest pain, reflux, nausea, vomiting, dysphagia, ulcer perforation, diarrhea, abdominal pain, headache, hepatic encephalopathy, spontaneous peritonitis, etc
Measured: 42 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Nov 2022
- Study start1 Oct 2023 (estimated)
- Primary completion31 Dec 2025 (estimated)
- Study completion31 Dec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Upper Gastrointestinal HemorrhageStudies of the same condition, open and under way.
- More trials run by West China HospitalThe sponsor's other registered studies.
- 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
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 672 participants (estimated)
Sponsor and investigators
- Lead sponsor
- West China Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, luo xuefeng, West China Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05624229
- Sponsor's protocol ID
- PPI-AVB
- Status last verified
- Sep 2023
- First submitted
- 12 Nov 2022
- Last updated
- 28 Sep 2023
- 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 28 Sep 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy of Proton Pump Inhibitors in Cirrhotic Patients With Acute Variceal Bleeding
- ClinicalTrials.gov ID
- NCT05624229
- Acronym / sponsor ID
- PPI-AVB
- Conditions
- Upper Gastrointestinal Hemorrhage
- Keywords
- Proton Pump Inhibitors, Acute Variceal Bleeding, Liver Cirrhosis, Endoscopic Variceal Ligation
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 672 participants (estimated)
- Lead sponsor
- West China HospitalUniversity, hospital or other
- Study start
- 1 Oct 2023 (estimated)
- Primary completion
- 31 Dec 2025 (estimated)
- Study completion
- 31 Dec 2028 (estimated)
- First posted
- 22 Nov 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.
Acute Variceal Bleeding (AVB) in patients with liver cirrhosis is a common clinical critical disease. There is little evidence for the effect of proton pump inhibitor (PPI) use in patients with AVB, and there is no study on the efficacy of PPI combined with standard therapy in patients with AVB.
Detailed description
AVB in patients with liver cirrhosis is a common clinical critical disease, with a 6-week mortality rate as high as 20%. Currently, many guidelines recommend the use of vasoactive drugs (terlipressin, somatostatin or octreotide) combined with endoscopic therapy (Endoscopic Variceal Ligation (EVL), endoscopic injection sclerotherapy (EIS) and the use of prophylactic antibiotics for patients with AVB.
PPI is a commonly used antacid agent, which has a significant antacid effect, protects the gastrointestinal mucosa, promotes blood coagulation, healing ulcers, effectively stops bleeding and prevents rebleeding. There is a consensus that PPI should be used before and after endoscopic therapy in patients with non-variceal acute bleeding. However, studies on the efficacy of PPI after EVL are still limited and lack of sufficient convincing. In a randomized controlled study, pantoprazole treatment was found to be associated with significantly smaller ulcers 10 days after elective EVL in secondary prevention patients with cirrhosis. Another randomized controlled study in 2013 found that patients with cirrhosis and AVB treated with PPI for 19 days after endoscopic hemostasis had smaller ulcers and fewer overall side-effects, but there was no statistically significant difference in rate of 5-day treatment failure, 6-week rebleeding rate and 6-week mortality. In 2017, a study included 637 patients with acute bleeding from liver cirrhosis, 80% of whom were treated with acid suppression therapy, and the study found that acid suppression therapy had no significant effect on long-term bleeding rate and mortality. However, negative effects of PPI have been reported in patients with cirrhosis, such as spontaneous bacterial peritonitis and hepatic encephalopathy. It is found that patients with cirrhosis and ascites had an increased risk of first hepatic encephalopathy with PPI use, and also found that patients with cirrhosis had an increased risk of hepatic encephalopathy and death with PPI use. Therefore, PPI use in patients with cirrhosis should be more cautious. However, the duration of PPI use in these studies was long, and there are no data to clarify the effect of short-term PPI use.
At present, there is no consensus among the major guidelines on the use of PPI in patients with acute AVB in liver cirrhosis, and the UK guidelines do not recommend the use of PPI unless accompanied by gastrointestinal ulcer. The use of PPI was not mentioned in the guidelines of the American Endoscopic Society and the European Endoscopic Society. The 2021 Baveno 7 guideline clearly proposes that PPI should be stopped immediately once AVB is identified as cirrhosis. The latest meta-analysis in 2022 showed that the use of PPI before endoscopy may reduce the need for endoscopic hemostasis in patients with upper gastrointestinal tract, but there was no sufficient evidence to confirm the effect on clinical outcomes including 30-day mortality and rebleeding. It can be concluded that there is no consensus on the use of PPI in patients with AVB in cirrhosis, and the recommendations of guidelines lack high-quality studies to improve the convincing.
In summary, there is little evidence for the effect of PPI use in patients with AVB in liver cirrhosis, and there is no study on the efficacy of PPI combined with endoscopic therapy in patients with AVB in liver cirrhosis. Therefore, the investigators planned to design a multicenter prospective randomized controlled trial to explore the efficacy of PPI in cirrhotic patients with AVB. In this study, the following questions were investigated: 1. Can PPI reduce the 5-day treatment failure rate in cirrhotic patients with AVB; 2. Can it reduce the 6-week rebleeding rate, mortality, and complications in patients with liver cirrhosis and AVB.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Standard group | Placebo comparator | Drug: No Proton Pump InhibitorsEarly treatment is mainly aimed at correcting hypovolemic shock, preventing gastrointestinal bleeding-related complications, effective control of bleeding, monitoring vital signs and urine output. Medical treatment included initiation and maintenance of vasoactive agents as soon as possible for 2 to 5 days, and prophylactic antibiotics (preferably ceftriaxone sodium or quinolones) by intravenous infusion for 5 days. Endoscopic intervention was performed within 12 hours after presentation and generally no longer than 24 hours. PPI was stopped immediately after endoscopic treatment. Early TIPS is determined according to the technology and concept of each unit. |
| Standard group+PPI | Experimental | Drug: Proton Pump InhibitorsPPI continued after endoscopic treatment for 5 days. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Liver cirrhosis.
- The etiology of portal hypertension is cirrhosis.
- Patients presenting with acute esophageal variceal bleeding proven by emergency endoscopy within 24 hours.
- Be willing to participate in this clinical study, comply with the study requirements and sign the informed consent
Key exclusion criteria (11 listed)
- non-cirrhotic portal hypertension
- the time from admission to endoscopy was more than 24 hours
- patients with peptic ulcer or gastroesophageal reflux disease requiring PPI therapy
- PPI use for more than 2 weeks before admission
- received endoscopic or interventional therapy within the previous 4 weeks
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 |
|---|---|---|
| Proton Pump InhibitorsAlso: Drug: Omeprazole, Drug: Esomeprazole, Drug: Rabeprazole, Drug: PantoprazolePPI infusion continued to use for 5 days in experimental group | Drug | Standard group+PPI |
| No Proton Pump InhibitorsPPI infusion stopped in standard group after endoscopy. | Drug | Standard group |
Primary outcome
5-day treatment failure rate
Time frame: 5 days
Failure of initial hemostasis Initial hemostasis was defined as not achieving a 24h bleeding-free period within the first 48h after treatment together with stable vital signs based on Baveno consensus criteria. UGI bleeding occurred after initial hemostasis and within 5 days after enrollment was defined as early rebleeding. UGI bleeding was proven to be from esophageal varices.
4 secondary outcomes
Rebleeding rate within 42 days
Time frame: 42 days
Mortality rate within 42 days
Time frame: 42 days
Rescure treatment
Time frame: 42 days
Compilcations
Time frame: 42 days
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Sep 2023.
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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.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Proton Pump Inhibitors and No Proton Pump Inhibitors in people with Upper Gastrointestinal Hemorrhage, run by West China Hospital.
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 4 inclusion and 11 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: opening soon, as of the sponsor's last update on 28 Sep 2023. 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. Some participants in this study may receive a placebo. 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?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
5-day treatment failure rate (time frame: 5 days). 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 28 Sep 2023.