Nrf2 Activator (Chlorophyllin) or Placebo With Standard Treatment for Late Radiation-induced Luminal Gastrointestinal Tract Bleeding: Multicentric Double-Blinded Phase III Randomised Trial
试验速览
- 阶段
- 3 期
- 状态
- 尚未招募
- 入组人数
- 200
- 试验地点
- 1
- 主要终点
- Grade 2 or higher anemia (CTCAE anemia version 5) due to uncontrolled bleeding
研究概览
简要总结
This multicenter, randomized, double-blind, placebo-controlled Phase III clinical trial will evaluate whether oral sodium copper chlorophyllin (CHL) is effective and safe for treating late radiation-induced gastrointestinal (GI) bleeding in patients who previously received radiotherapy for cancer. Radiation-induced GI bleeding can occur months or years after treatment and may lead to chronic bleeding, anemia, blood transfusions, and reduced quality of life. Current treatment options are often invasive, expensive, or only partially effective.
Eligible participants will be randomly assigned to receive either CHL 500 mg once daily or a matching placebo for 3 months, in addition to standard medical management, and will be followed for up to 2 years. The primary objective is to determine whether CHL reduces clinically significant anemia caused by radiation-induced GI bleeding at 6 months. Secondary objectives include evaluation of bleeding severity, gastrointestinal symptoms, endoscopic healing, blood transfusion requirements, quality of life, safety, and cost-effectiveness. The study aims to determine whether CHL can provide an effective, safe, and affordable treatment option for patients with chronic radiation-induced GI bleeding.
详细描述
Late radiation-induced gastrointestinal (GI) bleeding is a chronic complication that may develop months to years after radiotherapy for abdominal, pelvic, or mediastinal malignancies. Patients may experience persistent GI bleeding, anemia, recurrent blood transfusions, impaired quality of life, and repeated invasive procedures. Existing treatments, including argon plasma coagulation, hyperbaric oxygen therapy, and supportive medical management, have variable efficacy, limited availability, and may be associated with substantial cost or procedure-related risks.
Sodium copper chlorophyllin (CHL) is a semi-synthetic chlorophyll derivative that activates the Nrf2 pathway and has demonstrated antioxidant, anti-inflammatory, and radioprotective properties in preclinical studies. Early-phase clinical studies have shown a favorable safety profile and encouraging efficacy in radiation-induced toxicities, including hemorrhagic cystitis, supporting further evaluation in radiation-induced GI bleeding.
This is a multicenter, randomized, double-blind, placebo-controlled Phase III superiority trial. Approximately 200 participants with late radiation-induced luminal GI bleeding will be randomized in a 1:1 ratio to receive either oral CHL 500 mg once daily or matching placebo for 3 months, in addition to standard medical management. Participants will be followed for up to 2 years after randomization.
The primary endpoint is the occurrence of grade 2 or higher anemia attributable to radiation-induced GI bleeding at 6 months. Secondary endpoints include changes in bleeding severity, gastrointestinal symptoms, endoscopic response, occult blood test conversion, anemia-related laboratory parameters, blood transfusion requirements, quality of life, safety, breakthrough bleeding, rescue therapy requirements, and cost-effectiveness.
The study is designed to determine whether CHL can provide an effective, safe, and affordable treatment option for patients with chronic radiation-induced GI bleeding while reducing anemia, transfusion requirements, and healthcare costs and improving patient quality of life.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
This is a double-blind, placebo-controlled study. Participants, treating physicians, investigators involved in patient care, and blinded study statisticians will remain unaware of treatment assignment throughout the study. Sodium copper chlorophyllin (CHL) tablets and placebo tablets are identical in appearance, packaging, and labeling and are dispensed using unique bottle identification numbers. Treatment allocation is maintained by an independent unblinded statistician, who provides bottle numbers to the study pharmacist for dispensing. The randomization code will remain concealed until database lock or unless emergency unblinding is required for participant safety.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age greater than 18 years.
- •Histologically confirmed malignancy who have previously received radiotherapy to the pelvis, abdomen, or mediastinum and subsequently developed late radiation-induced luminal gastrointestinal bleeding at least 6 months after completion of radiotherapy.
- •Currently no evidence of distant metastases or local recurrence associated with GI bleed, documented and proven as appropriate with the primary diagnosis.
- •Site of GI bleed localised by either CT angiography or endscopy (Vienna score) or as per best standards applicable in institutional practice and primary diagnosis.
- •Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to
- •Ability to understand, voluntarily consent, and sign a written informed consent form prior to study participation.
- •Additional local symptoms associated with site of bleeding along with bleeding are allowed.
- •HB maintained >10 g/dl with or without transfusion before initiation of study intervention. Occult stool may be positive.
- •Previous bleed treatment failure (any, including HBOT/APC), or partial response to APC/HBOT or other treatment is allowed.
- •Patient reliable for follow-up for 2 years
排除标准
- •Diagnosed of ulcerative colitis or other histologically confirmed inflammatory bowel disease (IBD), disease such as ITP, TTP etc where patient may have bleeding tendencies which may be associated with GI bleed independently.
- •Presence of any other significant medical or psychiatric condition that, in the opinion of the investigator, may compromise the patient's safety, interfere with study participation or compliance, or confound interpretation of study results.
- •Poor anticipated compliance or follow-up reliability, as assessed by the investigator.
- •Failure to meet one or more inclusion criteria, rendering the patient ineligible for study participation.
- •Prophylactic use of Ecosprin, heparin, warfarin for certain medical conditions may be allowed.
研究组 & 干预措施
Sodium Copper Chlorophyllin (CHL)
Participants randomized to this arm will receive oral sodium copper chlorophyllin (CHL) 500 mg once daily for 3 months in addition to standard medical management for late radiation-induced gastrointestinal bleeding. Standard care may include supportive measures such as blood transfusions, hematinics, laxatives, tranexamic acid, sucralfate or enterofoam enema, and optimization of anticoagulant therapy as clinically indicated. Participants will be followed for up to 2 years.
干预措施: Chlorophyllin, Sodium Copper Complex (Drug)
Placebo
Participants randomized to this arm will receive matching placebo tablets once daily for 3 months in addition to standard medical management for late radiation-induced gastrointestinal bleeding. The placebo is identical in appearance, packaging, and labeling to the investigational product to maintain blinding. Participants will receive the same standard medical management and follow-up schedule as the experimental arm.
干预措施: Placebo (Drug)
结局指标
主要结局
Grade 2 or higher anemia (CTCAE anemia version 5) due to uncontrolled bleeding
时间窗: Up to 6 months after randomization
Grade 2 or higher anemia (CTCAE anemia version 5) due to uncontrolled bleeding defines failure of intervention. This will be actively evaluated at 1,3 and 6 months and for the intervention to be successful, Hb should be \>/=10gm/dl (at the same lab, where baseline Hb was evaluated) at 6 months from randomization. Interim Hb levels for unplanned patients visits and 1, 3 months will also be counted, where if Hb \<8gm/gl, then the intervention will be deemed unsuccessful without waiting for 6 months and patient will be managed as per institutional protocol. Patients may still be followed up for recording institutional practice (interventions) and outcomes till 2 years follow up is completed.
次要结局
- CB-Score (chronic bleeding score)(2 Years)
- Occult Blood Test Conversion Rate(2 Years)
- Symptom Relief in Associated GI Symptom Complex(2 Years)
- Endoscopic Response(2 Years)
- Anemia profile(2 Years)
- Cost of Therapy(2 Years)
- Transfusion Rates(2 Years)
- Quality of Life (QoL) QLQ-C30(2 Years)
- Quality of Life (QoL) QLQ-PRT-20(2 Years)
- Questionnaire LENT-SOMA(2 Years)
- Questionnaire EQ-5D-5L(2 Years)
- Breakthrough Bleeding(2 Years)
- Rescue Therapy Requirements(2 Years)