Long-term Effects of Thalidomide for Recurrent Gastrointestinal Bleeding Due to Vascular Malformation

This study has been completed.
Sponsor:
Information provided by:
Shanghai Jiao Tong University School of Medicine
ClinicalTrials.gov Identifier:
NCT00964496
First received: August 24, 2009
Last updated: September 1, 2010
Last verified: August 2009
  Purpose

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.


Condition Intervention Phase
Obscure Gastrointestinal Bleeding
Angiodysplasia
Gastric Antral Vascular Ectasia
Thalidomide
Drug: Thalidomide
Drug: Iron
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Long-term Effects of Thalidomide for Recurrent Gastrointestinal Bleeding Due to Vascular Malformation: An Open-label, Randomized, Parallel Controlled Study

Resource links provided by NLM:


Further study details as provided by Shanghai Jiao Tong University School of Medicine:

Primary Outcome Measures:
  • Participants Whose Rebleeds Decreased From Baseline by ≥ 50% at 12 Months [ Time Frame: baseline and 12 months ] [ Designated as safety issue: No ]
    The primary end point was defined as the patients whose rebleeds decreased from baseline by ≥ 50% at 12 months. Reduction of rebleeds = [(total bleeding episode at 12 months - total bleeding episodes at a year before randomization)/total bleeding episodes at a year before randomization(baseline)]*100%. Rebleeding was defined based on a positive fecal occult blood test (FOBT) (monoclonal colloidal gold color technology) at any visit after treatment.

  • Cessation of Bleeding [ Time Frame: 52 months ] [ Designated as safety issue: No ]
    The cessation of bleeding was defined as repeated negative faecal occult blood test (FOBT) (monoclonal colloidal gold color technology) during our observation period. Rebleeding was defined based on a positive FOBT at any visit after treatment.


Secondary Outcome Measures:
  • Change From Baseline in Hemoglobin (Hb) Level at 12 Months [ Time Frame: baseline and 12 months ] [ Designated as safety issue: No ]
    The change from baseline in average hemoglobin (Hb) level(tested every month) at 12 months.

  • Change From Baseline in Bleeding Episodes at 12 Months [ Time Frame: baseline and 12 months ] [ Designated as safety issue: No ]
    The Change from baseline in bleeding episodes at 12 months

  • Change From Baseline in Bleeding Duration at 12 Months [ Time Frame: baseline and 12 months ] [ Designated as safety issue: No ]
    The change from baseline in bleeding duration at 12 months

  • Participants Dependent on Blood Transfusions [ Time Frame: 52 months ] [ Designated as safety issue: No ]
    Numbers of participants dependent on blood transfusions

  • Change From Baseline in Total Transfused Red Cell Requirements at 12 Months [ Time Frame: baseline and 12 months ] [ Designated as safety issue: No ]
    Change of total transfused red cell requirements at 12 months after randomization from one year before baseline in transfusion dependent patients


Enrollment: 55
Study Start Date: November 2004
Study Completion Date: August 2009
Primary Completion Date: November 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Thalidomide Group Drug: Thalidomide
Patients were randomly assigned to receive a four-month course of 25 mg of thalidomide (Pharmaceutical Co., Ltd. of ChangZhou, China). Medications were taken orally four times daily at 6 a.m., 12 noon, 6 p.m., and 10 p.m.
Other Name: Softenon;
Iron-controlled Group Drug: Iron
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.
Other Name: Ferrous Succinate Tablets

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   40 Years to 85 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00964496

Sponsors and Collaborators
Shanghai Jiao Tong University School of Medicine
Investigators
Principal Investigator: Zhizheng Ge, MD. Ph.D Shanghai Ren Ji Hospital
  More Information

Additional Information:
Publications:
Responsible Party: Zhizheng Ge, MD. Ph.D ,Professor ,Shanghai Ren Ji Hospital, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine
ClinicalTrials.gov Identifier: NCT00964496     History of Changes
Other Study ID Numbers: rjyyxhk3015
Study First Received: August 24, 2009
Results First Received: August 26, 2009
Last Updated: September 1, 2010
Health Authority: China: Ethics Committee

Keywords provided by Shanghai Jiao Tong University School of Medicine:
vascular malformation
gastrointestinal bleeding
thalidomide

Additional relevant MeSH terms:
Vascular Malformations
Angiodysplasia
Congenital Abnormalities
Gastric Antral Vascular Ectasia
Gastrointestinal Hemorrhage
Hemorrhage
Cardiovascular Abnormalities
Cardiovascular Diseases
Digestive System Diseases
Gastrointestinal Diseases
Pathologic Processes
Stomach Diseases
Vascular Diseases
Thalidomide
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Anti-Bacterial Agents
Anti-Infective Agents
Antineoplastic Agents
Growth Inhibitors
Growth Substances
Immunologic Factors
Immunosuppressive Agents
Leprostatic Agents
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014