Long-term Effects of Thalidomide for Recurrent Gastrointestinal Bleeding Due to Vascular Malformation
Condition: Obscure Gastrointestinal Bleeding; Angiodysplasia; Gastric Antral Vascular Ectasia; Thalidomide
MeSH terms: Gastrointestinal Hemorrhage; Gastric Antral Vascular Ectasia; Vascular Malformations; Angiodysplasia; Congenital Abnormalities; Hemorrhage
Intervention: Thalidomide; Iron
Intervention description: Patients were randomly assigned to receive a four-month course of 25 mg of thalidomide (Pharmaceutical Co., Ltd. of Chang-zhou, China). Medications were taken orally four times daily at 6 a.m., 12 noon, 6 p.m., and 10 p.m.; Patients were randomly assigned to receive a four-month course of 100 mg of iron (Pharmaceutical Co., Ltd. of Nanjing, China). Medications were taken orally four times daily at 6 a.m., 12 noon, 6 p.m., and 10 p.m.
Intervention MeSH terms: Thalidomide; Ferrous succinate
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 55.0
Sex: All
Minimum age: 40 Years
Maximum age: 85 Years
Healthy volunteers: No
Keywords: vascular malformation; gastrointestinal bleeding; thalidomide

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 performed a randomized, parallel controlled study of thalidomide
      as a therapy for recurrent gastrointestinal bleeding due to vascular malformation. 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 25 mg of thalidomide or 100 mg of
      iron orally four times 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 and the
      cessation of bleeding. 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 participants dependent on blood transfusions and changes from baseline
      in transfused packed red cell units, bleeding episodes, bleeding durations, and hemoglobin
      levels at 12 months. Statistical significance was defined at P < 0.05.
    

Eligibility 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;

          -  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 were excluded if their bleeding history were less than 1 year;

          -  if they had cirrhotic or portal hypertension gastropathy; severe co-morbidities of
             cardiac, pulmonary, renal, liver, hematological, rheumatologic disorders, or
             uncontrollable diabetes mellitus or hypertension;

          -  if they had a history of severe bilateral peripheral neuropathy or seizure activity,
             thromboembolic disease, known thalidomide or iron allergy, or prior treatment of
             gastrointestinal bleeding with thalidomide;

          -  if they had 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

          -  if they were undergoing systemic cancer chemotherapy or receiving radiation.