CompletedNCT02707484Updated Jun 23, 2023

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

A Phase 3 interventional study of Thalidomide (100mg) and Thalidomide (50mg) in Gastrointestinal Vascular Malformation, sponsored by Shanghai Jiao Tong University School of Medicine. Completed at 10 sites in China. Open to participants aged 18 Years to 75 Years. Per ClinicalTrials.gov, last updated 2023-06-23.

Sponsored by Shanghai Jiao Tong University School of Medicine · Phase 3, Interventional, and Treatment

Phase: Phase 3
Study type: Interventional
Enrollment: 150
Allocation: Randomized
Ages: 18 Years to 75 Years
Sex: All

Study 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.

Read the detailed description

This multi-institutional clinical trial investigates the efficacy of thalidomide to the recurrent small intestinal hemorrhage due to GIVM. Patients with annual average bleeding 4 times or more and lesions located in the small intestine which are not suitable for endoscopic therapy will be randomly assigned to receive A(25mg,Thalidomide，qid), B(25mg, Thalidomide, bid\& placebo bid ) or placebo(deferred treatment group) for 4 months. The primary endpoints were the effective response of patients with ≥50% reduction of numbers of bleeding episodes, followed by rate of cases with cessation of bleedin, the difference in blood transfusion, hospitalization, transfusion volume of red cell, average bleeding duration, average hemoglobin level, yearly hospitalization times, average hospital stay and yearly bleeding episodes. This study will be done at 10 centers in China.

Conditions studied

Gastrointestinal Vascular Malformation

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Keywords

Gastrointestinal vascular malformation
thalidomide
Small intestinal bleeding

Who can participate

Ages eligible: 18 Years to 75 Years
Sexes eligible: All
Accepts healthy volunteers: No

Inclusion criteria

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.

Exclusion criteria

Exclusion Criteria:

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.

Study design

Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel assignment
Masking: Triple (Participant, Investigator, Outcomes assessor)
Enrollment: 150 participants (actual)

Study arms

Experimental
Thalidomide Group（100mg）
Generic name:Thalidomide Dosage form:tablet, 25mg Dosage:100mg/day Frequency: 25mg, QID, Oral Duration:120 days
Drug: Thalidomide (100mg)
Experimental
Thalidomide Group（50mg）
Generic name:Thalidomide Dosage form:tablet, 25mg\&Placebo Dosage:50mg/day Frequency: 25mg BID \&Placebo, BID, Oral Duration:120 days
Drug: Thalidomide (50mg)
Placebo comparator
placebo -controlled Group
Generic name:Thalidomide Placebo Dosage form:tablet, Placebo Dosage:Placebo Frequency: Placebo, QID, Oral Duration:120 days
Drug: placebo

Interventions

DrugThalidomide (100mg)
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
DrugThalidomide (50mg)
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
Drugplacebo
Patients were randomly assigned to receive a 120-days course of placebo (Pharmaceutical Co., Ltd. of ChangZhou, China).
Also known as: Group 3

What researchers measure

Primary outcomes

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.
Time frame: First 1-year follow-up versus the 1-year Observation Period.

Secondary outcomes

overall rate of cases with cessation of bleeding
The overall rate of cases with cessation of bleeding without rebleeding during the First 1-year Follow-up Period.
Time frame: First 1-year follow-up versus the 1-year Observation Period.
rate of cases requiring blood transfusion
The rate of cases requiring blood transfusion during the First 1-year follow-up.
Time frame: First 1-year follow-up versus the 1-year Observation Period.
rate of cases requiring hospitalizations due to bleeding
The rate of cases requiring hospitalizations due to bleeding during the 1st 1-year follow-up
Time frame: First 1-year follow-up versus the 1-year Observation Period.
change in the transfusion volume of red cell
The change in the transfusion volume of red cell during the First 1-year Follow-up Period versus the Observation Period.
Time frame: First 1-year follow-up versus the 1-year Observation Period.
change in average bleeding duration
The change in average bleeding duration (days) during the First 1-year Follow-up Period versus the Observation Period.
Time frame: First 1-year follow-up versus the 1-year Observation Period.
change in average hemoglobin level
The change in average hemoglobin level (g/L) during the First 1-year Follow-up Period versus the Observation Period.
Time frame: First 1-year follow-up versus the 1-year Observation Period.
change in yearly hospitalization times
The change in yearly hospitalization times due to bleeding during the First 1-year Follow-up Period versus the Observation Period.
Time frame: First 1-year follow-up versus the 1-year Observation Period.
change in average hospital stay
The change in average hospital stay (days)due to bleeding during the First 1-year Follow-up Period versus the Observation Period.
Time frame: First 1-year follow-up versus the 1-year Observation Period.
change in yearly bleeding episodes
The change in yearly bleeding episodes during the First 1-year Follow-up Period versus the Observation Period.
Time frame: First 1-year follow-up versus the 1-year Observation Period.

Study locations

10 sites

Peking Union Medical College Hospital
Beijing, Beijing 100032, China
Xinqiao Hospital of Chongqing
Chongqing, Chongqing 400037, China
Nanfang Hospital of Southern Medical University
Guangzhou, Guangdong 510515, China
Ruijin Hospital
Shanghai, Shanghai 200025, China
Shanghai Zhongshan Hospital
Shanghai, Shanghai 200032, China
Huashan Hospital
Shanghai, Shanghai 200040, China
Xinhua Hospital, Shanghai Jiao Tong University School of Medicine
Shanghai, Shanghai 200092, China
Department of Gastroenterology, Renji Hospital, Shanghai Institute of Digestive Diseases, Shanghai Jiao Tong University School of Medicine
Shanghai, Shanghai 200127, China
Changhai Hospital
Shanghai, Shanghai 200433, China
Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine
Shanghai, Shanghai 201620, China

References and documents

Publications

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. PubMed 21784047 ↗
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. PubMed 18031363 ↗
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. PubMed 22098296 ↗
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. PubMed 17254484 ↗
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. PubMed 21955427 ↗
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. PubMed 24219762 ↗

Registry details

Key details

Study ID: NCT02707484
Lead sponsor: Shanghai Jiao Tong University School of Medicine
Collaborators: Peking Union Medical College Hospital, Nanfang Hospital, Southern Medical University, Xinqiao Hospital of Chongqing, Changhai Hospital, Shanghai Zhongshan Hospital, Huashan Hospital, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Ruijin Hospital
Responsible party: Zhizheng Ge (Director of digestive endoscopy center of Renji hospital, Shanghai Jiao Tong University School of Medicine) — Principal investigator
First posted: Mar 14, 2016
Start date: Apr 2016
Primary completion: Dec 2020
Completion: Apr 2021
Last update: Jun 23, 2023

Oversight

Data monitoring committee: Yes

View the source record on ClinicalTrials.gov ↗

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