Ulcer BleedingNCT02352155
Second-look Endoscopy in High Risk Patients After Endoscopic Hemostasis to Their Bleeding Peptic Ulcers Improves Their Outcomes
A study testing epinephrine injection or heater probe or hemoclips and Observation only in people with Ulcer Bleeding, run by Chinese University of Hong Kong at 2 sites in 2 countries.
Trial summary
Bleeding peptic ulcer is a common medical emergency. Endoscopic treatment stops bleeding in those actively bleeding from their peptic ulcers, reduces further bleeding, transfusion, surgery and deaths. After initial endoscopic control of bleeding, approximately 10% of them will develop recurrent bleeding. Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- Ulcer Bleeding
- What is being tested?
- epinephrine injection or heater probe or hemoclips and Observation only
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 157 participants
- Where
- 2 sitesin 2 countries
- Study dates
- 4 Feb 2015to 2 Apr 2020
- Phase
- Interventional
- 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 to 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age >=18
- Informed consent obtained
- Successful endoscopic hemostasis
- Risk Score >= 5
Who cannot join
- Age < 18
- Pregnancy
- Incomplete endoscopic haemostasis -
Trial locations and contacts
2 sites in 2 countries.
2 sites in 2 countries
About this study
Bleeding peptic ulcer is a common medical emergency. Endoscopic treatment stops bleeding in those actively bleeding from their peptic ulcers, reduces further bleeding, transfusion, surgery and deaths. After initial endoscopic control of bleeding, approximately 10% of them will develop recurrent bleeding. Mortality rate in this group of patients is at least 4 fold higher. In the few who need surgery, mortality approaches 30%. Prevention of further bleeding is therefore a major treatment objective. Currently the investigators use a high dose infusion of proton pump inhibitor (PPI) for 72 hours to render gastric pH neutral. In a previous randomized trial, the investigators showed that the rate of bleeding in 30 days was around 7% with such an approach. In a small subgroup of high risk patients defined by presentation with shock and ulcers > 2 cm in size, 1 in 6 would re-bleed. An alternate strategy is to select those at especially high risk of further bleeding and repeat endoscopic treatment the next morning. The investigators have shown that persistence of major bleeding stigmata, i.e. a visible vessel, during a second endoscopy predicts further bleeding. It is therefore logical that by repeating endoscopic treatment the next morning, the investigators can prevent further bleeding and possibly surgery and deaths. The current study proposes to develop a score to identify those at risk of further bleeding after endoscopy. The investigators used a historical cohort with carefully collected clinical data to derive a risk score. In this derivation phase of 939 patients, the investigators have developed a 9 point risk score which consists of the following parameters (Age>60, Male sex, ulcer>2cm, posterior bulbar in location, spurting or Forrest Ia bleeding and admission hemoglobin of < 8 g/dl). Using AUROC and Youden J statistics, a score of 5 or above has been shown to highly predictive of further bleeding. The score will then be validated in a prospective cohort of patients with bleeding peptic ulcers. In the final phase of this study, the investigators propose a randomized controlled trial to test the hypothesis that a second look endoscopy with treatment in selected high risk patients can further reduce bleeding and improve their outcomes. After endoscopic hemostasis to their bleeding peptic ulcers, patients are risk stratified based on the score. Those with a score of 5 or more are randomized to receive the standard treatment (a high dose PPI infusion) or a second look endoscopy with treatment in addition to PPI infusion. The primary outcome to the trial is further significant clinical bleeding.
Read the detailed description
Hospitalization for bleeding peptic ulcers has declined over past decades [1]. Bleeding from peptic ulcers however remains the commonest diagnosis in those who present with acute upper gastrointestinal bleeding (AUGIB). The incidence has been around 60-80/100,000 population. Endoscopic hemostatic therapy is the first treatment to those with active bleeding and major stigmata of bleeding. Endoscopic therapy stops bleeding and reduces rate of further bleeding, requirement for surgery and importantly deaths [2]. Adjunctive intravenous infusion of a high dose proton pump inhibitor (PPI) further reduces rebleeding. In a multicentre international placebo controlled trial that involved 767 patients with bleeding peptic ulcers, a PPI infusion reduced the rate of further bleeding (10.3 to 5.9% at 72 hour, P=0.026) In a subgroup analysis of a Cochrane meta-analysis over use of PPI in bleeding peptic ulcers, the adjunctive use of PPI in those who underwent endoscopic hemostatic treatment, when compared to those without PPI therapy, was associated with a reduction in deaths (17/954 vs. 32/ 969; OR 0.54; 95%CI 0.3-0.96) [ 4 ] . Despite of aggressive endoscopic therapy and maximal acid suppression using a PPI infusion, further bleeding occurs in around 8% of patients. Further bleeding is the single most important adverse prognostic factor and is associated with a 4 fold increase in mortality. From a National United Kingdom Audit on the management of patients with AUGIB, those who needed surgery for further bleeding and failed endoscopic control had a mortality of 28% [ 5 ]. In addition to initial control of bleeding with endoscopic therapy, the prevention of further bleeding is an important objective.
The use of routine second look endoscopy with re-treatment has been evaluated in several clinical trials. A recent meta-analysis [ 6 ] of these clinical trials concluded that the use of routine second look endoscopy confers a modest reduction in rate of further bleeding. In this pooled analysis of 8 trials and 938 patients, the absolute risk reduction was 6.8% (16.5 to 9.7%). The number to treat to prevent one episode of recurrent bleeding was 15. Only one of these trials used high dose PPI infusion and epinephrine injection alone was used as endoscopic treatment. The use of epinephrine injection is no longer considered an optimal treatment. A second modality should be added to induce vessel thrombosis [ 7 ]. Clinical practice in the reported trials was considered not contemporary. In the modern practice of combination endoscopic treatment and maximal acid suppression, the use of routine second look endoscopy cannot be recommended as the NNT to prevent further bleeding would likely be higher. A policy of routine second look endoscopy is generally not recommended as suggested by an International Consensus Group [ 8 ].
Second look endoscopy in those at high risk of further bleeding is however a logical approach. The NNT to prevent further bleeding diminishes as risk of further bleeding increases. For instance, an ulcer > 2 cm in size with Forrest I or Forrest II a bleeding would be associated with a re-bleeding risk of 15-20% even with high dose PPI infusion. Saeed et al. reported a study consisted of a small number of patients (n=40) and showed that endoscopic re-treatment in selected high risk patients based on a Baylor College score led to significant reduction in further bleeding (0 vs. 24%). This selective approach warrants investigation and could represent a dominant strategy in addition to high dose PPI infusion as a pre-emptive management of patients at high risk of further bleeding. A prerequisite to this approach is a risk score that predicts further bleeding in patients after endoscopic hemostasis and PPI infusion. This risk score needs to be derived from a large cohort of patients after uniform endoscopic treatment and acid suppression. The score will have to be validated in a prospective cohort of patients with bleeding peptic ulcers again after the same aggressive treatment. Furthermore, a randomized controlled trial on the use of second look endoscopy in high risk patients as identified by this risk score is required.
- Conditions
- Ulcer Bleeding
- Being tested
- epinephrine injection or heater probe or hemoclips, Observation only
- Keywords
- haemostasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
epinephrine injection or heater probe or hemoclipsProcedure or surgery
Elective Second look endoscopy in the following morning with re-treatment to the bleeding vessel using epinephrine injection or heater probe or hemoclips
Observation onlyOther
Also called Observation for rebleeding
Observation for rebleeding, unscheduled endoscopy only when rebleeding criteria fulfilled
| Study group | Role | What they receive |
|---|---|---|
| Second look endoscopy | Active comparator | Second look endoscopy in the following morning with re-treatment to the bleeding vessel using epinephrine injection or heater probe or hemoclips Receives: Procedure: epinephrine injection or heater probe or hemoclips |
| observation only | Placebo comparator | NO second look endoscopy (Observation) Receives: Other: Observation only |
What is being measured
The primary outcome is the main question the study is designed to answer.
clinical significant bleeding
- fresh hematemesis or melena and 2) hypotensive with systolic blood pressure less than or equal to 90 mmHg and pulse rate of greater than or equal to 110 per minute and/ or a drop of haemoglobin of >2g/dl in 24 hours and a hematocrit of 0.24. Further bleeding has to be documented by endoscopic findings or fresh blood in the stomach together with a bleeding or non-bleeding visible vessel.
Measured: 30 days
Secondary outcomes (5)
additional intervention for further bleeding
additional intervention for further bleeding (surgery or angiographic intervention),
Measured: 30 days
blood transfusion
no. of participants with blood transfusion; median blood transfusion
Measured: 30 days
hospitalisation,
hospitalisation (including ICU stay)
Measured: 30 days
treatment related complications
no. of participants with ulcer perforation
Measured: 30 days
deaths from all causes
mortality, (related or not related to treatment ) cause of death
Measured: 30 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Feb 2015 (estimated)
- Study start4 Feb 2015
- Primary completion2 Apr 2020
- Study completion2 Apr 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Ulcer BleedingStudies of the same condition, open and under way.
- More trials run by Chinese University of Hong KongThe 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 157 participants (actual)
Sponsor and investigators
- Lead sponsor
- Chinese University of Hong Kong
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, James Yun-wong Lau, Chinese University of Hong Kong
- Investigators
- James Y LAU, Prof, Principal investigator, CUHK
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02352155
- Sponsor's protocol ID
- SLOGD
- Status last verified
- Jul 2020
- First submitted
- 15 Dec 2014
- Last updated
- 15 Jul 2020
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
Pittayanon R, Suen BY, Kongtub N, Tse YK, Rerknimitr R, Lau JYW. Scheduled second look endoscopy after endoscopic hemostasis to patients with high risk bleeding peptic ulcers: a Randomized Controlled Trial. Surg Endosc. 2022 Sep;36(9):6497-6506. doi: 10.1007/s00464-021-09004-w. Epub 2022 Jan 12.
PubMed 35020056
Study at a glance
From the registry record, last updated by the sponsor on 15 Jul 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Second-look Endoscopy in High Risk Patients After Endoscopic Hemostasis to Their Bleeding Peptic Ulcers Improves Their Outcomes
- ClinicalTrials.gov ID
- NCT02352155
- Acronym / sponsor ID
- SLOGD
- Conditions
- Ulcer Bleeding
- Keywords
- haemostasis
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 157 participants (actual)
- Lead sponsor
- Chinese University of Hong KongUniversity, hospital or other
- Study start
- 4 Feb 2015 (actual)
- Primary completion
- 2 Apr 2020 (actual)
- Study completion
- 2 Apr 2020 (actual)
- First posted
- 2 Feb 2015 (estimated)
- 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.
Bleeding peptic ulcer is a common medical emergency. Endoscopic treatment stops bleeding in those actively bleeding from their peptic ulcers, reduces further bleeding, transfusion, surgery and deaths. After initial endoscopic control of bleeding, approximately 10% of them will develop recurrent bleeding. Mortality rate in this group of patients is at least 4 fold higher. In the few who need surgery, mortality approaches 30%. Prevention of further bleeding is therefore a major treatment objective. Currently the investigators use a high dose infusion of proton pump inhibitor (PPI) for 72 hours to render gastric pH neutral. In a previous randomized trial, the investigators showed that the rate of bleeding in 30 days was around 7% with such an approach. In a small subgroup of high risk patients defined by presentation with shock and ulcers > 2 cm in size, 1 in 6 would re-bleed. An alternate strategy is to select those at especially high risk of further bleeding and repeat endoscopic treatment the next morning. The investigators have shown that persistence of major bleeding stigmata, i.e. a visible vessel, during a second endoscopy predicts further bleeding. It is therefore logical that by repeating endoscopic treatment the next morning, the investigators can prevent further bleeding and possibly surgery and deaths. The current study proposes to develop a score to identify those at risk of further bleeding after endoscopy. The investigators used a historical cohort with carefully collected clinical data to derive a risk score. In this derivation phase of 939 patients, the investigators have developed a 9 point risk score which consists of the following parameters (Age>60, Male sex, ulcer>2cm, posterior bulbar in location, spurting or Forrest Ia bleeding and admission hemoglobin of < 8 g/dl). Using AUROC and Youden J statistics, a score of 5 or above has been shown to highly predictive of further bleeding. The score will then be validated in a prospective cohort of patients with bleeding peptic ulcers. In the final phase of this study, the investigators propose a randomized controlled trial to test the hypothesis that a second look endoscopy with treatment in selected high risk patients can further reduce bleeding and improve their outcomes. After endoscopic hemostasis to their bleeding peptic ulcers, patients are risk stratified based on the score. Those with a score of 5 or more are randomized to receive the standard treatment (a high dose PPI infusion) or a second look endoscopy with treatment in addition to PPI infusion. The primary outcome to the trial is further significant clinical bleeding.
Detailed description
Hospitalization for bleeding peptic ulcers has declined over past decades [1]. Bleeding from peptic ulcers however remains the commonest diagnosis in those who present with acute upper gastrointestinal bleeding (AUGIB). The incidence has been around 60-80/100,000 population. Endoscopic hemostatic therapy is the first treatment to those with active bleeding and major stigmata of bleeding. Endoscopic therapy stops bleeding and reduces rate of further bleeding, requirement for surgery and importantly deaths [2]. Adjunctive intravenous infusion of a high dose proton pump inhibitor (PPI) further reduces rebleeding. In a multicentre international placebo controlled trial that involved 767 patients with bleeding peptic ulcers, a PPI infusion reduced the rate of further bleeding (10.3 to 5.9% at 72 hour, P=0.026) In a subgroup analysis of a Cochrane meta-analysis over use of PPI in bleeding peptic ulcers, the adjunctive use of PPI in those who underwent endoscopic hemostatic treatment, when compared to those without PPI therapy, was associated with a reduction in deaths (17/954 vs. 32/ 969; OR 0.54; 95%CI 0.3-0.96) [ 4 ] . Despite of aggressive endoscopic therapy and maximal acid suppression using a PPI infusion, further bleeding occurs in around 8% of patients. Further bleeding is the single most important adverse prognostic factor and is associated with a 4 fold increase in mortality. From a National United Kingdom Audit on the management of patients with AUGIB, those who needed surgery for further bleeding and failed endoscopic control had a mortality of 28% [ 5 ]. In addition to initial control of bleeding with endoscopic therapy, the prevention of further bleeding is an important objective.
The use of routine second look endoscopy with re-treatment has been evaluated in several clinical trials. A recent meta-analysis [ 6 ] of these clinical trials concluded that the use of routine second look endoscopy confers a modest reduction in rate of further bleeding. In this pooled analysis of 8 trials and 938 patients, the absolute risk reduction was 6.8% (16.5 to 9.7%). The number to treat to prevent one episode of recurrent bleeding was 15. Only one of these trials used high dose PPI infusion and epinephrine injection alone was used as endoscopic treatment. The use of epinephrine injection is no longer considered an optimal treatment. A second modality should be added to induce vessel thrombosis [ 7 ]. Clinical practice in the reported trials was considered not contemporary. In the modern practice of combination endoscopic treatment and maximal acid suppression, the use of routine second look endoscopy cannot be recommended as the NNT to prevent further bleeding would likely be higher. A policy of routine second look endoscopy is generally not recommended as suggested by an International Consensus Group [ 8 ].
Second look endoscopy in those at high risk of further bleeding is however a logical approach. The NNT to prevent further bleeding diminishes as risk of further bleeding increases. For instance, an ulcer > 2 cm in size with Forrest I or Forrest II a bleeding would be associated with a re-bleeding risk of 15-20% even with high dose PPI infusion. Saeed et al. reported a study consisted of a small number of patients (n=40) and showed that endoscopic re-treatment in selected high risk patients based on a Baylor College score led to significant reduction in further bleeding (0 vs. 24%). This selective approach warrants investigation and could represent a dominant strategy in addition to high dose PPI infusion as a pre-emptive management of patients at high risk of further bleeding. A prerequisite to this approach is a risk score that predicts further bleeding in patients after endoscopic hemostasis and PPI infusion. This risk score needs to be derived from a large cohort of patients after uniform endoscopic treatment and acid suppression. The score will have to be validated in a prospective cohort of patients with bleeding peptic ulcers again after the same aggressive treatment. Furthermore, a randomized controlled trial on the use of second look endoscopy in high risk patients as identified by this risk score is required.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Second look endoscopy | Active comparator | Procedure: epinephrine injection or heater probe or hemoclipsSecond look endoscopy in the following morning with re-treatment to the bleeding vessel using epinephrine injection or heater probe or hemoclips |
| observation only | Placebo comparator | Other: Observation onlyNO second look endoscopy (Observation) |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Age >=18
- Informed consent obtained
- Successful endoscopic hemostasis
- Risk Score >= 5
Key exclusion criteria (3 listed)
- Age < 18
- Pregnancy
- Incomplete endoscopic haemostasis -
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 |
|---|---|---|
| epinephrine injection or heater probe or hemoclipsElective Second look endoscopy in the following morning with re-treatment to the bleeding vessel using epinephrine injection or heater probe or hemoclips | Procedure or surgery | Second look endoscopy |
| Observation onlyAlso: Observation for rebleedingObservation for rebleeding, unscheduled endoscopy only when rebleeding criteria fulfilled | Other | observation only |
Primary outcome
clinical significant bleeding
Time frame: 30 days
1) fresh hematemesis or melena and 2) hypotensive with systolic blood pressure less than or equal to 90 mmHg and pulse rate of greater than or equal to 110 per minute and/ or a drop of haemoglobin of >2g/dl in 24 hours and a hematocrit of 0.24. Further bleeding has to be documented by endoscopic findings or fresh blood in the stomach together with a bleeding or non-bleeding visible vessel.
5 secondary outcomes
additional intervention for further bleeding
Time frame: 30 days
blood transfusion
Time frame: 30 days
hospitalisation,
Time frame: 30 days
treatment related complications
Time frame: 30 days
deaths from all causes
Time frame: 30 days
Results and safety
The study was stopped early. Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Jul 2020.
- Derived from this study: PubMed 35020056Pittayanon R, Suen BY, Kongtub N, Tse YK, Rerknimitr R, Lau JYW. Scheduled second look endoscopy after endoscopic hemostasis to patients with high risk bleeding peptic ulcers: a Randomized Controlled Trial. Surg Endosc. 2022 Sep;36(9):6497-6506. doi: 10.1007/s00464-021-09004-w. Epub 2022 Jan 12.
- Individual participant dataSharing planned: No
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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.
James Y LAU, Prof principal investigator
CUHK
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing epinephrine injection or heater probe or hemoclips and Observation only in people with Ulcer Bleeding, run by Chinese University of Hong Kong at 2 sites in 2 countries.
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 3 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: stopped early, as of the sponsor's last update on 15 Jul 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in China, Thailand. Whether a site is taking part right now should be confirmed with that site. See every site.
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.
Are results available for this study?
The study was stopped early. Results are not available in the source record.
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?
clinical significant bleeding (time frame: 30 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02352155, which also lists 1 linked publication.
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 Jul 2020.