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

NCT00964496 | Completed Phase 2 Results

• 1 other identifier: rjyyxhk3015
• Study Type: interventional
• Target: 55
• Locations: 0 countries
• Sites: N/A

Brief 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.

Conditions

Obscure Gastrointestinal Bleeding; Angiodysplasia; Gastric Antral Vascular Ectasia; Thalidomide

Keywords

vascular malformation; gastrointestinal bleeding; thalidomide

Outcome Measures

Primary Outcomes (2)

• Participants Whose Rebleeds Decreased From Baseline by ≥ 50% at 12 Months

  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.

  baseline and 12 months

• Cessation of Bleeding

  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.

  52 months

Secondary Outcomes (5)

• Change From Baseline in Hemoglobin (Hb) Level at 12 Months

  baseline and 12 months

• Change From Baseline in Bleeding Episodes at 12 Months

  baseline and 12 months

• Change From Baseline in Bleeding Duration at 12 Months

  baseline and 12 months

• Participants Dependent on Blood Transfusions

  52 months

• Change From Baseline in Total Transfused Red Cell Requirements at 12 Months

  baseline and 12 months

Study Arms (2)

Thalidomide Group

ACTIVE COMPARATOR

Drug: Thalidomide

Iron-controlled Group

OTHER

Drug: Iron

Interventions

Thalidomide DRUG

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.

Also known as: Softenon;

Thalidomide Group

Iron DRUG

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.

Also known as: Ferrous Succinate Tablets

Iron-controlled Group

Eligibility Criteria

• Age: 40 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Shanghai Jiao Tong University School of Medicine: lead

Related Publications (3)

• Jacobson JM, Greenspan JS, Spritzler J, Ketter N, Fahey JL, Jackson JB, Fox L, Chernoff M, Wu AW, MacPhail LA, Vasquez GJ, Wohl DA. Thalidomide for the treatment of oral aphthous ulcers in patients with human immunodeficiency virus infection. National Institute of Allergy and Infectious Diseases AIDS Clinical Trials Group. N Engl J Med. 1997 May 22;336(21):1487-93. doi: 10.1056/NEJM199705223362103.

  PMID: 9154767 BACKGROUND

• Bauditz J, Schachschal G, Wedel S, Lochs H. Thalidomide for treatment of severe intestinal bleeding. Gut. 2004 Apr;53(4):609-12. doi: 10.1136/gut.2003.029710.

  PMID: 15016759 BACKGROUND

• Shurafa M, Kamboj G. Thalidomide for the treatment of bleeding angiodysplasias. Am J Gastroenterol. 2003 Jan;98(1):221-2. doi: 10.1111/j.1572-0241.2003.07201.x. No abstract available.

  PMID: 12526972 BACKGROUND

Related Links

• Approved drug page at FDA's Drugs@FDA web site.

MeSH Terms

Conditions

Angiodysplasia; Gastric Antral Vascular Ectasia; Vascular Malformations; Gastrointestinal Hemorrhage

Interventions

Thalidomide; Iron; ferrous succinate

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases; Stomach Diseases; Gastrointestinal Diseases; Digestive System Diseases; Cardiovascular Abnormalities; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Metals, Heavy; Elements; Inorganic Chemicals; Transition Elements; Metals

Limitations and Caveats

Single center, open-label study; lack of placebo pills, make it impossible on equality of dosages between two groups; lack of dose response assessment either in patients or assays of serum vascular endothelial growth factor.

Results Point of Contact

• Title: Zhizheng Ge, MD. Ph.D. Director of the Clinical Trials
• Organization: Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine

zhizhengge@yahoo.com.cn

86-21-68383015

Study Officials

• Zhizheng Ge, MD. Ph.D

  Shanghai Ren Ji Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: August 24, 2009
• First Posted: August 25, 2009
• Study Start: November 1, 2004
• Primary Completion: November 1, 2007
• Study Completion: August 1, 2009
• Last Updated: December 17, 2015
• Results First Posted: April 30, 2010

Record last verified: 2009-08