Clinical trial NCT04408261: BuqitongluO Granule for Qi Deficiency and Blood Stasis Syndrome
Official title: Buqitongluo Granule for Qi Deficiency and Blood Stasis Syndrome: A Multicenter, Randomized, Double-blind, Placebo-Controlled Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Stroke, Ischemic
Coronary Artery Disease
Angina Pectoris, Stable
Diabetic Peripheral Neuropathy
Keywords: Qi Deficiency and Blood Stasis Syndrome
Buqitongluo Granule
Traditional Chinese Medicine
Double-Blind
Randomized Controlled Trial
Lead sponsor: Dongzhimen Hospital, Beijing
Sponsor class: OTHER
Collaborators: name: The Affiliated Hospital of Changchun University of Chinese Medicine
name: The Affiliated Hospital of Shandong University of Chinese Medicine
name: The Affiliated Hospital of Chengdu University of Chinese Medicine
name: The Second Affiliated Hospital of Tianjin University of Traditional Chinese Medicine
name: The First Affiliated Hospital of Heilongjiang University of Traditional Chinese Medicine
name: The Second Affiliated Hospital of Heilongjiang University of Traditional Chinese Medicine
name: The Second Affiliated Hospital of Hunan University of Traditional Chinese Medicine
name: Hunan Academy of Traditional Chinese Medicine Affiliated Hospital
name: The First Clinical Hospital of Jilin Academy of Traditional Chinese Medicine
name: Shaanxi Buchang Pharmaceuticals Co., Ltd.
name: Beijing Chuanglikechuang Medical Technology Development Co., Ltd.
name: Shanghai Youningwei Biotechnology Co., Ltd.
name: Wuhan Zhizhi Medical Technology Co., Ltd.
name: Wuhan Third Hospital
name: Rizhao Hospital of Traditional Chinese Medicine
name: The First Affiliated Hospital of Guangxi University of Traditional Chinese Medicine
name: Jiangbin Hospital of Guangxi Zhuang Autonomous Region
First posted: 2020-05-29
Enrollment: 432
Sex: ALL
Minimum age (years): 35
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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).

Eligibility criteria: 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.

Primary outcomes:
measure: Change in the syndrome score of Qi Deficiency and Blood Stasis
timeFrame: Baseline, at day 14, day 28, day 42 during treatment, and at day 14 after treatment
Secondary outcomes:
measure: Neurological impairment will be evaluated by National Institute of Health Stroke Scale (NIHSS) for convalescence of ischemic stroke
timeFrame: Baseline, at day 14, day 28, day 42 during treatment
measure: Self-rating symptoms will be evaluated by Visual Analog Scale (VAS) for convalescence of ischemic stroke
timeFrame: Baseline, at day 14, day 28, day 42 during treatment, and at day 14 after treatment
measure: Continuous changes of Modified Rankin Scale for convalescence of ischemic stroke
timeFrame: Baseline, at day 42 during treatment, and at 90 days after onset
measure: Activities of daily living will be measured by Barthel Index (BI) score for convalescence of ischemic stroke
timeFrame: Baseline, at day 42 during treatment, and at 90 days after onset
measure: Quality of life will be measured by Short Form 36 (SF-36) Quality of Life Scale for convalescence of ischemic stroke
timeFrame: Baseline, at day 42 during treatment, and at 90 days after onset
measure: Change of the Seattle Angina Questionnaire (SAQ) Score for stable angina pectoris of coronary artery disease
timeFrame: Baseline, at day 28 during treatment, at day 14 after treatment, and at 90 days after recruitment
measure: Self-rating symptoms will be evaluated by Visual Analog Scale (VAS) for stable angina pectoris of coronary artery disease
timeFrame: Baseline, at day 14, day 28, day 42 during treatment, and at day 14 after treatment
measure: Change of the Clinical Scoring System of Toronto (TCSS) for diabetic peripheral neuropathy
timeFrame: Baseline, at day 14, day 28, day 42 during treatment, at day 14 after treatment, and at 90 days after recruitment
measure: Self-rating symptoms will be evaluated by Visual Analog Scale (VAS) for diabetic peripheral neuropathy
timeFrame: Baseline, at day 14, day 28, day 42 during treatment, and at day 14 after treatment
measure: 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
timeFrame: Baseline, at day 42 during treatment, and at 90 days after recruitment
Other outcomes:
Locations:
city: Beijing
country: China
facility: Dongzhimen Hospital
state: Beijing
Study officials:
affiliation: Dongzhimen Hospital
name: Ying Gao, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.