Gastrointestinal HemorrhagePhase 3NCT00787436
Secondary Prophylaxis of Gastrointestinal Bleeding in Cirrhotic Patients Using THALIDOMIDE
A Phase 3 study testing Thalidomide in people with Gastrointestinal Hemorrhage and Portal Hypertension, run by The Cleveland Clinic at 1 site in United States.
Trial summary
The natural history of cirrhosis has a symptomatic and asymptomatic stage. The symptoms include the development of ascites, hepatic encephalopathy, or variceal bleeding. The development of portal hypertension represents a critical transition point in the natural history of cirrhosis, contributing to, or directly… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Gastrointestinal Hemorrhage, Portal Hypertension
- What is being tested?
- Thalidomide
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- May 2006to Jan 2010
- Phase
- Phase 3
- 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
- Endoscopic confirmation or portal hypertension related GI bleeding
- Over the age of 18 with the ability to willingly sign an informed consent
- Adequate performance status and cognitive ability
- Patients must be willing to comply with all FDA-mandated prescribing and safety while taking Thalidomide
- Hemodynamically stable with no evidence of ongoing bleeding (defined as a Hgb that has not varied by more than 10% over 12 hour period.)
Who cannot join
- No other serious illness or medical condition including unstable cardiac disease requiring treatment, new onset crescendo or rest angina. Stable exertional angina is acceptable.
- No history of significant neurological or psychiatric disorders including psychotic disorders, dementia, or seizures or active infection
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Secondary Prophylaxis of Gastrointestinal Bleeding in Cirrhotic Patients Using Thalidomide
The natural history of cirrhosis has a symptomatic and asymptomatic stage. The symptoms include the development of ascites, hepatic encephalopathy, or variceal bleeding. The development of portal hypertension represents a critical transition point in the natural history of cirrhosis, contributing to, or directly responsible for all of these events. It is defined by an increase in intrahepatic vascular resistance to portal venous inflow, with the subsequent development of collateral vessels, such as esophageal or gastric varices. As portal pressures rise over time, however, the resulting increase in variceal size and wall tension translates into an increasing likelihood of rupture and bleeding, leading to death in about 30% of patients. Over the last twenty years, data have emerged regarding the role of tumor necrosis factor (TNFα) in portal hypertension from animal models as well as in vitro experiments. Portal hypertension is a condition characterized by vasodilatation and a hyperdynamic circulation, driven by relative overproduction of nitric oxide23. In animal trials using inhibitors of TNF it has been shown to decrease the development of the hyperdynamic circulatory state and portal pressure.24-25 Based on these data, investigators have examined the role of TNF inhibition with thalidomide. Significant improvement in blocking the development of the hyperdynamic circulation and portal pressures was demonstrated.26 Human trials have also show the efficacy of thalidomide in reducing portal pressures. In that these trials have shown promising results further investigation is
Read the detailed description
Treatment duration with thalidomide will be for 16 weeks, beginning in the hospital setting immediately after the index bleed, and clinical follow-up additional six months. Follow-up in both the hepatology, outpatient clinic area and the endoscopy suite will occur. Step wise thalidomide dosing will be 100 mg/d once a day at night. If no evidence of toxicity is noted after 5 doses, the dose will be increased to 200 mg/d, and continued on that dose as an outpatient until completion of the study protocol at 16 weeks. Patients will be followed daily while inpatients, and subsequently at two-week intervals upon discharge. Females of child-bearing potential will be seen weekly for the first month and must have a confirmed negative pregnancy test prior to being dispensed the next one week supply of study drug. After the first month, females of child-bearing potential will be seen every two weeks as will all other subjects. Standard follow-up medical care after esophageal variceal bleeding in patients who have undergone endoscopic therapy will include:
follow-up endoscopy at regular intervals until variceal obliteration, using either endoscopic variceal ligation (EVL) or sclerotherapy titrated dose of a nonselective beta blocker (propranolol).
At each follow-up visit, patients will be assessed for development of any interim outcome of interest:
overt upper gastrointestinal bleeding need for transfusion worsening clinical status
Patients will initially be followed daily while hospitalized. outpatient visits will occur every two-week intervals upon discharge. Standard follow-up medical care after esophageal variceal bleeding in patients who have undergone endoscopic therapy will include:
follow-up endoscopy at regular intervals until variceal obliteration, using either endoscopic variceal ligation (EVL) or sclerotherapy titrated dose of a nonselective beta blocker (propranolol).
At each follow-up visit, patients will be assessed for development of any interim outcome of interest:
overt upper gastrointestinal bleeding need for transfusion worsening clinical status the need for TIPS, liver transplantation or death. In addition, patients and their families will be questioned for any evidence of potential toxicity as assessed by using the CTC Toxicity grade version 3, or adverse outcomes by one of the study investigators as well as a nurse coordinator, using a standardized questionnaire along with a regular clinical
- Conditions
- Gastrointestinal Hemorrhage, Portal Hypertension
- Being tested
- Thalidomide
- Keywords
- portal hypertension, Gastroesophageal, Varices, Liver disease, cirrhosis
- Medical subject headings
- Gastrointestinal Hemorrhage, Hypertension, Portal, Varicose Veins, Liver Diseases, Fibrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ThalidomideDrug
Also called propranolol, nadolol, timolol
Medical therapy has been used to decrease upper gastrointestinal bleeding in cirrhotics Non Selective beta blockers have been shown to effectively decrease the portal venous pressure
| Study group | Role | What they receive |
|---|---|---|
| 1 | No intervention | Standard of care with normal treatment |
| Thalidomide | Active comparator | Standard of care and treatment using Thalidomide Receives: Drug: Thalidomide |
What is being measured
The primary outcome is the main question the study is designed to answer.
The proposed study would use a novel approach to prophylaxis, using thalidomide, an oral TNF inhibitor, in conjunction with a betablocker to prevent rebleeding of upper gastrointestinal bleeding in patients with cirrhosis and portal hyperte
Measured: 16 week duration
Secondary outcomes (1)
The secondary endpoint is to examine the impact on progression of liver disease in this population, including development of other complications of chronic liver disease, such as encephalopathy, hepatorenal syndrome and patient survival
Measured: 16 week duration
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Nov 2008 (estimated)
- Study startMay 2006
- Primary completionJan 2010
- Study completionJan 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Gastrointestinal HemorrhageStudies of the same condition, open and under way.
- More trials run by The Cleveland ClinicThe 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 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- The Cleveland Clinic
- Sponsor type
- University, hospital or other
- Collaborators
- Celgene Corporation
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00787436
- Sponsor's protocol ID
- CEL-20237
- Other IDs
- IRB00000536, FWA00005367, 34-0714585, OSR-20070905-01
- Status last verified
- Jul 2013
- First submitted
- 5 Nov 2008
- Last updated
- 31 Jul 2013
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 31 Jul 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Secondary Prophylaxis of Gastrointestinal Bleeding in Cirrhotic Patients Using Thalidomide
- ClinicalTrials.gov ID
- NCT00787436
- Acronym / sponsor ID
- CEL-20237
- Conditions
- Gastrointestinal Hemorrhage, Portal Hypertension
- Keywords
- portal hypertension, Gastroesophageal, Varices, Liver disease, cirrhosis
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Withdrawn
- Enrolment
- 0 participants (actual)
- Lead sponsor
- The Cleveland ClinicUniversity, hospital or other
- Collaborators
- Celgene Corporation
- Study start
- May 2006
- Primary completion
- Jan 2010 (actual)
- Study completion
- Jan 2010 (actual)
- First posted
- 7 Nov 2008 (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.
The natural history of cirrhosis has a symptomatic and asymptomatic stage. The symptoms include the development of ascites, hepatic encephalopathy, or variceal bleeding. The development of portal hypertension represents a critical transition point in the natural history of cirrhosis, contributing to, or directly responsible for all of these events. It is defined by an increase in intrahepatic vascular resistance to portal venous inflow, with the subsequent development of collateral vessels, such as esophageal or gastric varices. As portal pressures rise over time, however, the resulting increase in variceal size and wall tension translates into an increasing likelihood of rupture and bleeding, leading to death in about 30% of patients. Over the last twenty years, data have emerged regarding the role of tumor necrosis factor (TNFα) in portal hypertension from animal models as well as in vitro experiments. Portal hypertension is a condition characterized by vasodilatation and a hyperdynamic circulation, driven by relative overproduction of nitric oxide23. In animal trials using inhibitors of TNF it has been shown to decrease the development of the hyperdynamic circulatory state and portal pressure.24-25 Based on these data, investigators have examined the role of TNF inhibition with thalidomide. Significant improvement in blocking the development of the hyperdynamic circulation and portal pressures was demonstrated.26 Human trials have also show the efficacy of thalidomide in reducing portal pressures. In that these trials have shown promising results further investigation is
Detailed description
Treatment duration with thalidomide will be for 16 weeks, beginning in the hospital setting immediately after the index bleed, and clinical follow-up additional six months. Follow-up in both the hepatology, outpatient clinic area and the endoscopy suite will occur. Step wise thalidomide dosing will be 100 mg/d once a day at night. If no evidence of toxicity is noted after 5 doses, the dose will be increased to 200 mg/d, and continued on that dose as an outpatient until completion of the study protocol at 16 weeks. Patients will be followed daily while inpatients, and subsequently at two-week intervals upon discharge. Females of child-bearing potential will be seen weekly for the first month and must have a confirmed negative pregnancy test prior to being dispensed the next one week supply of study drug. After the first month, females of child-bearing potential will be seen every two weeks as will all other subjects. Standard follow-up medical care after esophageal variceal bleeding in patients who have undergone endoscopic therapy will include:
follow-up endoscopy at regular intervals until variceal obliteration, using either endoscopic variceal ligation (EVL) or sclerotherapy titrated dose of a nonselective beta blocker (propranolol).
At each follow-up visit, patients will be assessed for development of any interim outcome of interest:
overt upper gastrointestinal bleeding need for transfusion worsening clinical status
Patients will initially be followed daily while hospitalized. outpatient visits will occur every two-week intervals upon discharge. Standard follow-up medical care after esophageal variceal bleeding in patients who have undergone endoscopic therapy will include:
follow-up endoscopy at regular intervals until variceal obliteration, using either endoscopic variceal ligation (EVL) or sclerotherapy titrated dose of a nonselective beta blocker (propranolol).
At each follow-up visit, patients will be assessed for development of any interim outcome of interest:
overt upper gastrointestinal bleeding need for transfusion worsening clinical status the need for TIPS, liver transplantation or death. In addition, patients and their families will be questioned for any evidence of potential toxicity as assessed by using the CTC Toxicity grade version 3, or adverse outcomes by one of the study investigators as well as a nurse coordinator, using a standardized questionnaire along with a regular clinical
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | No intervention | –Standard of care with normal treatment |
| Thalidomide | Active comparator | Drug: ThalidomideStandard of care and treatment using Thalidomide |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Endoscopic confirmation or portal hypertension related GI bleeding
- Over the age of 18 with the ability to willingly sign an informed consent
- Adequate performance status and cognitive ability
- Patients must be willing to comply with all FDA-mandated prescribing and safety while taking Thalidomide
- Hemodynamically stable with no evidence of ongoing bleeding (defined as a Hgb that has not varied by more than 10% over 12 hour period.)
Key exclusion criteria (2 listed)
- No other serious illness or medical condition including unstable cardiac disease requiring treatment, new onset crescendo or rest angina. Stable exertional angina is acceptable.
- No history of significant neurological or psychiatric disorders including psychotic disorders, dementia, or seizures or active infection
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 |
|---|---|---|
| ThalidomideAlso: propranolol, nadolol, timololMedical therapy has been used to decrease upper gastrointestinal bleeding in cirrhotics Non Selective beta blockers have been shown to effectively decrease the portal venous pressure | Drug | Thalidomide |
Primary outcome
The proposed study would use a novel approach to prophylaxis, using thalidomide, an oral TNF inhibitor, in conjunction with a betablocker to prevent rebleeding of upper gastrointestinal bleeding in patients with cirrhosis and portal hyperte
Time frame: 16 week duration
1 secondary outcome
The secondary endpoint is to examine the impact on progression of liver disease in this population, including development of other complications of chronic liver disease, such as encephalopathy, hepatorenal syndrome and patient survival
Time frame: 16 week duration
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Jul 2013.
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Thalidomide in people with Gastrointestinal Hemorrhage and Portal Hypertension, run by The Cleveland Clinic at 1 site in United States.
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 5 inclusion and 2 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: withdrawn, as of the sponsor's last update on 31 Jul 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. 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. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
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?
The proposed study would use a novel approach to prophylaxis, using thalidomide, an oral TNF inhibitor, in conjunction with a betablocker to prevent rebleeding of upper gastrointestinal bleeding in patients with cirrhosis and portal hyperte (time frame: 16 week duration). 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 31 Jul 2013.