Retreatment and Its Efficiency of Thalidomide for Vascular Malformation Patients With Failure of First Course Treatment

• Status: Withdrawn
• Trial end date: 2018-12-01
• Target enrollment: 0
• Participant gender: All

Summary

Background: Repeated episodes of bleeding from gastrointestinal vascular malformations refractory to endoscopic or surgical therapy often pose a major therapeutic challenge.

Methods: The investigators will perform a randomized, double blind, placebo controlled study of thalidomide as a retreatment therapy for recurrent gastrointestinal bleeding due to vascular malformation. Patients with failure of first course treatment of thalidomide will be randomly grouped, prescribed a second four-month course regimen of 25 mg of thalidomide or placebo orally four times daily. All patients will be monitored for at least one year. The primary end point is defined as the patients whose rebleeds decrease from baseline by ≥ 50% at 12 months and the cessation of bleeding. Rebleeding is defined based on a positive fecal occult blood test (FOBT) (monoclonal colloidal gold color technology) at any visit after treatment. Secondary outcomes include the participants dependent on blood transfusions and changes from baseline in transfused packed red cell units, bleeding episodes, and hemoglobin levels at 12 months. Statistical significance is defined at P < 0.05.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Zhizheng Ge
• Treatments: Thalidomide

Criteria

Inclusion Criteria:

• Age between 35-85 years; women are post-menopausal, post-tubal ligation, or on some form of birth control like long-term laying up contraceptive ring or using condom;

• Patients with failure of first course treatment of thalidomide, which means rebleeds decreased from baseline by< 50% at 12 months follow up ;

• History of at least six documented gastrointestinal bleeding episodes in the year prior first course thalidomide treatment, which are refractory or inaccessible to endoscopic therapy or surgical ectomy; so, patients should have at least four episodes of gastrointestinal bleeding a year prior our study;

• Confirmed diagnosis of vascular malformation by esophagogastroduodenoscopy (EGD), capsule endoscope (CE), double-balloon endoscope (DBE), or colonoscopy, but no obvious infectious, neoplastic, or other specific diagnosis;

• Angiodysplasia at endoscopy characterized by focal or diffused venous/capillary lesions presenting as bright red ectatic vessels or pulsatile red protrusions, with surrounding venous dilatation or patchy erythema with or without oozing;

• Endoscopic appearance of GAVE (also known as watermelon stomach), indicated by longitudinal antral folds converging on the pylorus, containing visible columns of tortuous red ecstatic vessels.

Exclusion Criteria:

• Patients are excluded if first course treatment of thalidomide is effective, which means rebleeds decreased from baseline by ≥ 50% at 12 months follow up;

• if they have cirrhotic or portal hypertension gastropathy; severe co-morbidities of cardiac, pulmonary, renal, liver, hematological, rheumatologic disorders, or uncontrollable diabetes mellitus or hypertension;

• if they have a history of severe bilateral peripheral neuropathy or seizure activity, thromboembolic disease, known thalidomide allergy;

• if they have a history of treatment with any dose of systemic or oral topical corticosteroids or aspirin, NSAIDs, anti-platelet drugs, anticoagulants, or Chinese medications (with salicylates), gingko, or Echinacea, or other putative immunomodulators or anti-angiogenic agents;

• Currently pregnant or lactating or currently undergoing systemic cancer chemotherapy or receiving radiation