Efficacy Study of Thalidomide in Gastrointestinal Vascular Malformation Related Bleeding

• Status: Withdrawn
• Trial end date: 2014-09-01
• Target enrollment: 0
• Participant gender: All

Summary

Background: Repeated bleeding from gastrointestinal vascular malformations remains to be a major therapeutic challenge.

Methods: The investigators performed a randomised, double-blind, placebo-controlled, single centre study to assess the long-term efficacy and safety of thalidomide 100mg qn p.o. or placebo 100 mg qn p.o. administration for 4 months in subjects with recurrent gastrointestinal bleeding due to vascular malformations. Patients with at least six episodes of bleeding in the prior year due to vascular malformation were randomly grouped, prescribed a four-month regimen of either 100mg of thalidomide or 100 mg of placebo orally one time daily, and monitored for at least one year. The primary end point was defined as the patients whose rebleeds decreased from baseline by ≥ 50% at 12 months. Rebleeding was defined based on a positive fecal occult blood test (FOBT) (monoclonal colloidal gold color technology) at any visit after treatment. Secondary outcomes included the changes from baseline in participants dependent on blood transfusions and transfused packed red cell units, bleeding episodes, bleeding durations, and hemoglobin levels at 12 months. Statistical significance was defined at P < 0.05.

• Phase: Phase 2
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Shanghai Jiao Tong University School of Medicine
• Treatments: Thalidomide

Criteria

Inclusion Criteria:

• Age between 40-85 years; women were post-menopausal, post-tubal ligation, or on some form of birth control like long-term laying up contraceptive ring or using condom;

• History of at least six documented gastrointestinal bleeding episodes in the year prior to randomization, which were refractory or inaccessible to endoscopic therapy or surgical ectomy;

• 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;

Exclusion Criteria:

• Less than 1 year of bleeding history;

• GI bleeding caused by Esophageal varices, Mallory Weiss syndrome, Zollinger-Ellison syndrome, Suspicion of gastric malignancy at baseline endoscopy, Post-Billroth-resection, Biliary disorders, Gastrointestinal tumors, Crohn's disease or Ulcerative colitis, Hemangioma or unknown source of GI bleeding;

• Bleeding that needs emergent endoscopic treatment or surgery;

• Any significant "alarm symptoms" within the past 6 months, such as, unintentional weight loss, signs of gastrointestinal bleeding more than 2 weeks prior to enrolment, jaundice, or any other sign indicating serious or malignant disease;

• Malignancy or clinically significant cardiovascular, pulmonary, renal, pancreatic, hepatic disease, cirrhotic or portal hypertension gastropathy, rheumatologic disorders, uncontrollable diabetes mellitus or hypertension as judged by the investigator;

• A history of severe bilateral peripheral neuropathy or seizure activity, thromboembolic disease;

• 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;

• Haemorrhagic disorders, platelets<100 x 109/ L, APTT>1.5x upper limit of normal (ULN), or treatment with low-molecular weight heparin;

• Need for continuous concurrent therapy during the study period with NSAIDs, ASA (including low dose),Warfarin (including other Vit K antagonists), anti-platelet drugs, anticoagulants, mephenytoin, atazanavir or Chinese medications (with salicylates), gingko, or Echinacea, or other putative immunomodulators or anti-angiogenic agents;

• Pregnancy or lactation. Woman of child-bearing potential must be either non-pregnant or postmenopausal or must use a reliable form of contraception during the study period, as judged by the investigator;

• Allergy to study medications;

• Currently undergoing systemic cancer chemotherapy or receiving radiation or had underwent systemic cancer chemotherapy or received radiation treatment.

• Use of any other investigational compound or participation in another clinical trial within 30 days prior to start of study medication;

• Alcohol and/or drug abuse (addiction or drug dependence) or any condition associated with poor compliance, including expected non-cooperation, as judged by the investigator;

• Previous participation in the study;

• Involvement in the planning and conduct of the study.