BuqitongluO Granule for Qi Deficiency and Blood Stasis Syndrome (BOSS)

Buqitongluo Granule for Qi Deficiency and Blood Stasis Syndrome: A Multicenter, Randomized, Double-blind, Placebo-Controlled Trial

The main purpose of this trial is to evaluate the efficacy and safety of Buqitongluo Granule in treating qi deficiency and blood stasis syndrome, and explore the effect of the improvement of qi deficiency and blood stasis syndrome on the prognosis of diseases.

Study Overview

• Status: Unknown
• Conditions: Coronary Artery Disease; Diabetic Peripheral Neuropathy; Stroke, Ischemic; Angina Pectoris, Stable
• Intervention / Treatment: Drug: Buqitongluo Granule; Other: Standard care; Drug: Buqitongluo Granule Placebo

Detailed Description

The BOSS study is a multicenter, randomized, double-blind, placebo-controlled clinical trial. The primary hypothesis of this trial is that Buqitongluo Granule will improve the syndrome score of Qi Deficiency and Blood Stasis in convalescence of ischemic stroke, stable angina pectoris of coronary artery disease and diabetic peripheral neuropathy with qi deficiency and blood stasis syndrome. Buqitongluo Granule will be compared to placebo, combined with guidelines-based standard care in patients. During the trial, it is forbidden to use acupuncture, Traditional Chinese Medicine decoction (compound granule), Traditional Chinese Medicine injection, Chinese patent medicine (including external use), external washing of Traditional Chinese Medicine and health product (composition or efficacy similar to the study drug).

• Study Type: Interventional
• Enrollment (Anticipated): 432
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100700
      • Recruiting
      • Dongzhimen Hospital
      • Contact: Weidi Liu; Phone Number: 0086-15301025939; Email: L305613099@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 35 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Convalescence of ischemic stroke

Inclusion Criteria:

• Diagnosis of qi deficiency and blood stasis syndrome
• Diagnosis of ischemic stroke
• Age ≥ 35 and ≤ 80 years
• The interval from the onset to recruitment was 14-30 days
• NIHSS score ≥ 4 and ≤ 22
• Patient or legally authorized representative has signed informed consent.

Exclusion Criteria:

• Confirmed secondary stroke caused by tumor, brain trauma, or hematological diseases by clinical examination;
• Other conditions that lead to motor dysfunction (e.g. lameness, osteoarthrosis, rheumatoid arthritis, gouty arthritis), which render the neurological function examination unlikely to be assessed;
• Uncontrolled hypertension (systolic blood pressure ≥ 160 mmHg or diastolic blood pressure ≥ 100 mmHg), or renal or hepatic insufficiency (hepatic insufficiency is defined as an alanine aminotransferase (ALT) or aspartate aminotransferase (AST) value that is 1.5 times the upper limit of normal, renal insufficiency is defined as a serum creatinine concentration value that is over the upper limit of normal);
• Other conditions or mental disorders which according to the judgement of researchers that restrict evaluation of mental function or render outcomes or follow-up unlikely to be assessed;
• Woman with pregnancy, lactation, or woman who wants to be pregnant in recent;
• Patient who is allergic to the study drug or has severe allergic constitution;
• Patient with yellow thick slimy tongue coating;
• Patient who has been participated in other drug or device clinical trials in recent 3 months.

Stable angina pectoris of coronary artery disease

Inclusion Criteria:

• Diagnosis of qi deficiency and blood stasis syndrome
• Diagnosis of stable angina pectoris of coronary artery disease
• Age ≥ 35 and ≤ 80 years
• Canadian Cardiovascular Society (CCS) Classification of Angina Pectoris classⅠ-Ⅲ
• Patient or legally authorized representative has signed informed consent.

Exclusion Criteria:

• Acute coronary syndrome or unstable angina pectoris in the prior 3 months, or other heart diseases (e.g. cardiomyopathy, pericardial disease);
• Severe cardiopulmonary insufficiency (congestive heart failure NYHA class IV, severe abnormal pulmonary function), or severe arrhythmias (e.g. rapid atrial fibrillation, atrial flutter, paroxysmal ventricular tachycardia);
• Uncontrolled hypertension (systolic blood pressure ≥ 160 mmHg or diastolic blood pressure ≥ 100 mmHg), or renal or hepatic insufficiency (hepatic insufficiency is defined as an alanine aminotransferase (ALT) or aspartate aminotransferase (AST) value that is 1.5 times the upper limit of normal, renal insufficiency is defined as a serum creatinine concentration value that is over the upper limit of normal);
• Other conditions or mental disorders which according to the judgement of researchers that restrict evaluation of mental function or render outcomes or follow-up unlikely to be assessed;
• Woman with pregnancy, lactation, or woman who wants to be pregnant in recent;
• Patient who is allergic to the study drug or has severe allergic constitution;
• Patient with yellow thick slimy tongue coating;
• Patient who has been participated in other drug or device clinical trials in recent 3 months.

Diabetic peripheral neuropathy

Inclusion Criteria:

• Diagnosis of qi deficiency and blood stasis syndrome
• Diagnosis of diabetic peripheral neuropathies
• Age ≥ 35 and ≤ 80 years
• Patient or legally authorized representative has signed informed consent.

Exclusion Criteria:

• HbA1c >10% in the screening period;
• Acute critical disease of diabetes mellitus in the prior 3 months (e.g. hyperglycemia and hypertonic syndrome, diabetic lactic acidosis, diabetic ketoacidosis);
• Severe heart disease, brain disease, or kidney disease;
• Uncontrolled hypertension (systolic blood pressure ≥ 160 mmHg or diastolic blood pressure ≥ 100 mmHg), or renal or hepatic insufficiency (hepatic insufficiency is defined as an alanine aminotransferase (ALT) or aspartate aminotransferase (AST) value that is 1.5 times the upper limit of normal, renal insufficiency is defined as a serum creatinine concentration value that is over the upper limit of normal);
• Patient with spinal cord injury, cervical or lumbar vertebra disease (nerve root compression, spinal stenosis, cervical or lumbar vertebra degenerative disease), or sequelae of cerebrovascular disease, neuromuscular junction or muscular disease;
• Neuropathies caused by other diseases (e.g. Guillain-Barre syndrome, chronic inflammatory demyelinating polyneuropathy (CIDP), VitB deficiency, hypothyroidism, alcoholism, severe arteriovenous vasculopathy such as venous embolism, lymphangitis);
• Other conditions or mental disorders which according to the judgement of researchers that restrict evaluation of mental function or render outcomes or follow-up unlikely to be assessed;
• Woman with pregnancy, lactation, or woman who wants to be pregnant in recent;
• Patient who is allergic to the study drug or has severe allergic constitution;
• Patient with yellow thick slimy tongue coating;
• Patient with red tongue and scanty tongue coating;
• Patient who has been participated in other drug or device clinical trials in recent 3 months.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Buqitongluo Granule; Subjects will receive orally administered Buqitongluo Granules, combined with guidelines-based standard care.	Drug: Buqitongluo Granule; Buqitongluo Granules were dissolved with boiled water, administered orally, each bag of 10 grams, one bag each time, three times a day for 42 days.; Other: Standard care; Guidelines-based standard care for convalescence of ischemic stroke, stable angina pectoris of coronary artery disease or diabetic peripheral neuropathy.
PLACEBO_COMPARATOR: Placebo; Subjects will receive orally administered Buqitongluo Granule placeboes, combined with guidelines-based standard care.	Other: Standard care; Guidelines-based standard care for convalescence of ischemic stroke, stable angina pectoris of coronary artery disease or diabetic peripheral neuropathy.; Drug: Buqitongluo Granule Placebo; Buqitongluo Granule placeboes were dissolved with boiled water, administered orally, each bag of 10 grams, one bag each time, three times a day for 42 days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in the syndrome score of Qi Deficiency and Blood Stasis	The dynamic evaluation will be defined by Evaluation Scale of Qi Deficiency and Blood Stasis Syndrome. The Evaluation Scale of Qi Deficiency and Blood Stasis Syndrome score ranges from 0 (best score) to 51 (worst score).	Baseline, at day 14, day 28, day 42 during treatment, and at day 14 after treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Neurological impairment will be evaluated by National Institute of Health Stroke Scale (NIHSS) for convalescence of ischemic stroke	The NIHSS score ranges from 0 (best score) to 42 (worst score).	Baseline, at day 14, day 28, day 42 during treatment
Self-rating symptoms will be evaluated by Visual Analog Scale (VAS) for convalescence of ischemic stroke	Including limb numbness, swelling of hands or feet, spontaneous sweating (hemilateral sweating). Participants rated their symptoms on the 100 millimeter (mm) Visual Analog Scale (VAS) ranging from 0 mm (no symptom) to 100 mm (worst symptom).	Baseline, at day 14, day 28, day 42 during treatment, and at day 14 after treatment
Continuous changes of Modified Rankin Scale for convalescence of ischemic stroke	The Modified Rankin Scale score ranges from 0 (best score) to 6 (worst score).	Baseline, at day 42 during treatment, and at 90 days after onset
Activities of daily living will be measured by Barthel Index (BI) score for convalescence of ischemic stroke	The Barthel Index score ranges from 0 (worst score) to 100 (best score).	Baseline, at day 42 during treatment, and at 90 days after onset
Quality of life will be measured by Short Form 36 (SF-36) Quality of Life Scale for convalescence of ischemic stroke	The SF-36 quality of life scale is used to monitor change in subject reported functionality, well-being, and overall health status. The score of each part ranges from 0 (worst score) to 100 (best score).	Baseline, at day 42 during treatment, and at 90 days after onset
Change of the Seattle Angina Questionnaire (SAQ) Score for stable angina pectoris of coronary artery disease	The maximum score is 100, and the higher the score, the better the quality of life and the state of body function of patient.	Baseline, at day 28 during treatment, at day 14 after treatment, and at 90 days after recruitment
Self-rating symptoms will be evaluated by Visual Analog Scale (VAS) for stable angina pectoris of coronary artery disease	Including chest tightness, chest pain, palpitation, fatigue, spontaneous sweating. Participants rated their symptoms on the 100 millimeter (mm) Visual Analog Scale (VAS) ranging from 0 mm (no symptom) to 100 mm (worst symptom).	Baseline, at day 14, day 28, day 42 during treatment, and at day 14 after treatment
Change of the Clinical Scoring System of Toronto (TCSS) for diabetic peripheral neuropathy	TCSS includes a score of neural symptoms, nerve reflex scores and sensory examination. The TCSS score ranges from 0 (best score) to 19 (worst score).	Baseline, at day 14, day 28, day 42 during treatment, at day 14 after treatment, and at 90 days after recruitment
Self-rating symptoms will be evaluated by Visual Analog Scale (VAS) for diabetic peripheral neuropathy	Including local pain, limb numbness, paresthesia (e.g. burning sensation, formication, electrical sensation). Participants rated their symptoms on the 100 millimeter (mm) Visual Analog Scale (VAS) ranging from 0 mm (no symptom) to 100 mm (worst symptom).	Baseline, at day 14, day 28, day 42 during treatment, and at day 14 after treatment
Quality of life will be measured by Short Form 36 (SF-36) Quality of Life Scale for stable angina pectoris of coronary artery disease and diabetic peripheral neuropathy	The SF-36 quality of life scale is used to monitor change in subject reported functionality, well-being, and overall health status. The score of each part ranges from 0 (worst score) to 100 (best score).	Baseline, at day 42 during treatment, and at 90 days after recruitment

Collaborators and Investigators

• Sponsor: Dongzhimen Hospital, Beijing
• Collaborators: Wuhan Third Hospital; The Second Affiliated Hospital of Tianjin University of Traditional Chinese Medicine; The Second Affiliated Hospital of Hunan University of Traditional Chinese Medicine; Hunan Academy of Traditional Chinese Medicine Affiliated Hospital; The Affiliated Hospital of Changchun University of Chinese Medicine; The Affiliated Hospital of Shandong University of Chinese Medicine; The Affiliated Hospital of Chengdu University of Chinese Medicine; The First Affiliated Hospital of Heilongjiang University of Traditional Chinese Medicine; The Second Affiliated Hospital of Heilongjiang University of Traditional Chinese Medicine; The First Clinical Hospital of Jilin Academy of Traditional Chinese Medicine; Shaanxi Buchang Pharmaceuticals Co., Ltd.; Beijing Chuanglikechuang Medical Technology Development Co., Ltd.; Shanghai Youningwei Biotechnology Co., Ltd.; Wuhan Zhizhi Medical Technology Co., Ltd.; Rizhao Hospital of Traditional Chinese Medicine; The First Affiliated Hospital of Guangxi University of Traditional Chinese Medicine; Jiangbin Hospital of Guangxi Zhuang Autonomous Region

Publications and helpful links

General Publications

• Liu W, Zhou L, Feng L, Zhang D, Zhang C, Gao Y; behalf of the BOSS Group. BuqiTongluo Granule for Ischemic Stroke, Stable Angina Pectoris, Diabetic Peripheral Neuropathy with Qi Deficiency and Blood Stasis Syndrome: Rationale and Novel Basket Design. Front Pharmacol. 2021 Oct 18;12:764669. doi: 10.3389/fphar.2021.764669. eCollection 2021.

Study record dates

Study Major Dates

• Study Start (ACTUAL): July 22, 2020
• Primary Completion (ANTICIPATED): December 1, 2022
• Study Completion (ANTICIPATED): December 1, 2022

Study Registration Dates

• First Submitted: May 26, 2020
• First Submitted That Met QC Criteria: May 26, 2020
• First Posted (ACTUAL): May 29, 2020

Study Record Updates

• Last Update Posted (ACTUAL): April 1, 2021
• Last Update Submitted That Met QC Criteria: March 29, 2021
• Last Verified: May 1, 2020

More Information

Terms related to this study

• Keywords: Double-Blind; Randomized Controlled Trial; Traditional Chinese Medicine; Qi Deficiency and Blood Stasis Syndrome; Buqitongluo Granule
• Additional Relevant MeSH Terms: Digestive System Diseases; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Metabolic Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Pain; Neurologic Manifestations; Gastrointestinal Diseases; Neuromuscular Diseases; Intestinal Diseases; Coronary Disease; Malabsorption Syndromes; Stroke; Chest Pain; Coronary Artery Disease; Ischemic Stroke; Peripheral Nervous System Diseases; Angina Pectoris; Angina, Stable; Blind Loop Syndrome
• Other Study ID Numbers: 2017L04609

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No