the Efficiency of Thalidomide for Recurrent Small Intestinal Bleeding Due to Gastrointestinal Vascular Malformation

NCT02707484 | Completed Phase 3 DMC

• 1 other identifier: rj(2015)088K-a
• Study Type: interventional
• Target: 150
• Locations: 1 country
• Sites: 10

Brief Summary

Gastrointestinal vascular malformation (GIVM), which is an important cause of acute or chronic gastrointestinal bleeding, currently lacks of effective treatment. The investigators' previous study first confirmed thalidomide treatment of GIVM bleeding was safe and effective. This prospective multi-center randomized controlled clinical trial intends to investigate the efficacy of thalidomide to the recurrent small intestinal hemorrhage due to GIVM.

Conditions

Gastrointestinal Vascular Malformation

Keywords

Gastrointestinal vascular malformation; thalidomide; Small intestinal bleeding

Outcome Measures

Primary Outcomes (1)

• effective response rate

  the proportion of patients with "effective treatment, patients with ≥50% reduction of numbers of bleeding episodes after treatment during the First 1-year follow-up versus the 1-year Observation Period.

  First 1-year follow-up versus the 1-year Observation Period.

Secondary Outcomes (9)

• overall rate of cases with cessation of bleeding

  First 1-year follow-up versus the 1-year Observation Period.

• rate of cases requiring blood transfusion

  First 1-year follow-up versus the 1-year Observation Period.

• rate of cases requiring hospitalizations due to bleeding

  First 1-year follow-up versus the 1-year Observation Period.

• change in the transfusion volume of red cell

  First 1-year follow-up versus the 1-year Observation Period.

• change in average bleeding duration

  First 1-year follow-up versus the 1-year Observation Period.

Study Arms (3)

Thalidomide Group（100mg）

EXPERIMENTAL

Generic name:Thalidomide Dosage form:tablet, 25mg Dosage:100mg/day Frequency: 25mg, QID, Oral Duration:120 days

Drug: Thalidomide (100mg)

Thalidomide Group（50mg）

EXPERIMENTAL

Generic name:Thalidomide Dosage form:tablet, 25mg\&Placebo Dosage:50mg/day Frequency: 25mg BID \&Placebo, BID, Oral Duration:120 days

Drug: Thalidomide (50mg)

placebo -controlled Group

PLACEBO COMPARATOR

Generic name:Thalidomide Placebo Dosage form:tablet, Placebo Dosage:Placebo Frequency: Placebo, QID, Oral Duration:120 days

Drug: placebo

Interventions

Thalidomide (100mg) DRUG

Patients were randomly assigned to receive a 120-days course of 100 mg of thalidomide (Pharmaceutical Co., Ltd. of ChangZhou, China).

Also known as: Group 1

Thalidomide Group（100mg）

Thalidomide (50mg) DRUG

Patients were randomly assigned to receive a 120-days course of 50 mg of thalidomide (Pharmaceutical Co., Ltd. of ChangZhou, China).

Also known as: Group 2

Thalidomide Group（50mg）

placebo DRUG

Patients were randomly assigned to receive a 120-days course of placebo (Pharmaceutical Co., Ltd. of ChangZhou, China).

Also known as: Group 3

placebo -controlled Group

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects voluntarily signed the informed consent after the nature and the specific procedures of the trial has been verbally explained; they have the opportunity to ask questions.
• Chinese nationality;
• Female or male subjects aged 18-75 years. Female subjects must be menopausal or have undergone sterilization such as tubal ligation and hysterectomy, or have no plan to give birth recently and agree to take contraceptive measures such as contraceptive drugs, intrauterine physical birth control rings or contraception condoms; or men must have undergone sterilization or do not plan to have a child recently and agree to take contraceptive measures such as contraceptive drugs, or contraception condoms. These criteria are set to eliminate the risk of subjects of child bearing potential.
• The subjects must have been diagnosed, by capsule endoscopy and / or balloon-assisted enteroscopy, with small intestinal vascular malformation lesions which are unsuitable or inaccessible to endoscopic therapy or surgical antrectomy. Subjects with persistent, recurrent bleeding, ≥ 4 episodes of overt or occult bleeding over last year.

You may not qualify if:

• Subjects with esophageal varices from cirrhosis of the liver; those with uncontrolled hypertension or hyperglycemia (or diabetics who are being treated with insulin), or those with severe heart (e.g., uncontrolled angina pectoris and / or myocardial infarction, congestive heart failure, etc.), respiratory failure, or renal failure with creatinine (Cr) or blood urea nitrogen (BUN) \> 2 times the upper limit of normal (ULN), pancreatic or hepatic disease with abnormal hepatic function with alanine aminotransferase (ALT), aspartate aminotransferase (AST) or total bilirubin (TBil) \> 2 times ULN 3 months before the enrollment, or those with any other diseases that are not suitable for the study as judged by the Investigator;
• Subjects with a history of severe peripheral neuropathy or seizures, or a history of thromboembolic disease;
• Subjects who need to continuously use non-steroidal anti-inflammatory drugs, anticoagulants, antiplatelets, acetylsalicylic acid preparations, or Chinese herbal medicines containing ginkgo and echinacea; or those who need to receive other anti-angiogenic drugs for a long time;
• Subjects with white blood cell counts persistently \<3.5 \* 10\^9 / L;
• Subjects with a history of small bowel resection;
• Subjects known or suspected to be allergic to any component of thalidomide；
• Subjects with severe gastrointestinal bleeding that is life-threatening and requires immediate surgical treatment;
• Subjects who have previously received thalidomide for gastrointestinal bleeding 30 days before the enrollment;
• Alcohol and / or substance abusers with addiction or dependence, or those with poor compliance as judged by a doctor;
• Subjects who participated in other clinical trial 6 months before enrollment;
• Subjects without legal capacity or self-awareness.

Sponsors & Collaborators

• Shanghai Jiao Tong University School of Medicine: lead
• Peking Union Medical College Hospital: collaborator
• Nanfang Hospital, Southern Medical University: collaborator
• Xinqiao Hospital of Chongqing: collaborator
• Changhai Hospital: collaborator
• Shanghai Zhongshan Hospital: collaborator
• Huashan Hospital: collaborator
• Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine: collaborator
• Xinhua Hospital, Shanghai Jiao Tong University School of Medicine: collaborator
• Ruijin Hospital: collaborator

Study Sites (10)

Peking Union Medical College Hospital

Beijing, Beijing Municipality, 100032, China

Location

Xinqiao Hospital of Chongqing

Chongqing, Chongqing Municipality, 400037, China

Location

Nanfang Hospital of Southern Medical University

Guangzhou, Guangdong, 510515, China

Location

Ruijin Hospital

Shanghai, Shanghai Municipality, 200025, China

Location

Shanghai Zhongshan Hospital

Shanghai, Shanghai Municipality, 200032, China

Location

Huashan Hospital

Shanghai, Shanghai Municipality, 200040, China

Location

Xinhua Hospital, Shanghai Jiao Tong University School of Medicine

Shanghai, Shanghai Municipality, 200092, China

Location

Department of Gastroenterology, Renji Hospital, Shanghai Institute of Digestive Diseases, Shanghai Jiao Tong University School of Medicine

Shanghai, Shanghai Municipality, 200127, China

Location

Changhai Hospital

Shanghai, Shanghai Municipality, 200433, China

Location

Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine

Shanghai, Shanghai Municipality, 201620, China

Location

Related Publications (7)

• Ge ZZ, Chen HM, Gao YJ, Liu WZ, Xu CH, Tan HH, Chen HY, Wei W, Fang JY, Xiao SD. Efficacy of thalidomide for refractory gastrointestinal bleeding from vascular malformation. Gastroenterology. 2011 Nov;141(5):1629-37.e1-4. doi: 10.1053/j.gastro.2011.07.018. Epub 2011 Jul 22.

  PMID: 21784047 RESULT

• Ge ZZ, Chen HY, Gao YJ, Hu YB, Xiao SD. Best candidates for capsule endoscopy for obscure gastrointestinal bleeding. J Gastroenterol Hepatol. 2007 Dec;22(12):2076-80. doi: 10.1111/j.1440-1746.2006.04724.x.

  PMID: 18031363 RESULT

• Tan H, Chen H, Xu C, Ge Z, Gao Y, Fang J, Liu W, Xiao S. Role of vascular endothelial growth factor in angiodysplasia: an interventional study with thalidomide. J Gastroenterol Hepatol. 2012 Jun;27(6):1094-101. doi: 10.1111/j.1440-1746.2011.06967.x.

  PMID: 22098296 RESULT

• Li XB, Ge ZZ, Dai J, Gao YJ, Liu WZ, Hu YB, Xiao SD. The role of capsule endoscopy combined with double-balloon enteroscopy in diagnosis of small bowel diseases. Chin Med J (Engl). 2007 Jan 5;120(1):30-5.

  PMID: 17254484 RESULT

• Tan HH, Ge ZZ, Gao YJ, Chen HM, Fang JY, Chen HY, Liu WZ, Xiao SD. The role of HIF-1, angiopoietin-2, Dll4 and Notch1 in bleeding gastrointestinal vascular malformations and thalidomide-associated actions: a pilot in vivo study. J Dig Dis. 2011 Oct;12(5):349-56. doi: 10.1111/j.1751-2980.2011.00506.x.

  PMID: 21955427 RESULT

• Feng Q, Tan HH, Ge ZZ, Gao YJ, Chen HM, Xiao SD. Thalidomide-induced angiopoietin 2, Notch1 and Dll4 downregulation under hypoxic condition in tissues with gastrointestinal vascular malformation and human umbilical vein endothelial cells. J Dig Dis. 2014 Feb;15(2):85-95. doi: 10.1111/1751-2980.12114.

  PMID: 24219762 RESULT

• Chen H, Wu S, Tang M, Zhao R, Zhang Q, Dai Z, Gao Y, Yang S, Li Z, Du Y, Yang A, Zhong L, Lu L, Xu L, Shen X, Liu S, Zhong J, Li X, Lu H, Xiong H, Shen Y, Chen H, Gong S, Xue H, Ge Z. Thalidomide for Recurrent Bleeding Due to Small-Intestinal Angiodysplasia. N Engl J Med. 2023 Nov 2;389(18):1649-1659. doi: 10.1056/NEJMoa2303706.

  PMID: 37913505 DERIVED

MeSH Terms

Interventions

Thalidomide

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

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of digestive endoscopy center of Renji hospital

Study Record Dates

• First Submitted: November 17, 2015
• First Posted: March 14, 2016
• Study Start: April 1, 2016
• Primary Completion: December 1, 2020
• Study Completion: April 1, 2021
• Last Updated: June 23, 2023

Record last verified: 2023-06

Locations

CN (10)