The Effect of Berberine on Intestinal Function and Inflammatory Mediators in Severe Patients With Covid-19
Keywords
Abstract
Description
Patients aged 18-80 years who confirmed with COVID-19 and classified as severe were enrolled in the study, and then separated randomly into two groups: a berberine group (B group) and a control group (C group). The diagnostic criteria for severe cases are in accordance with the Diagnosis and Treatment Guideline of patients with COVID-19 issued by the National Health Commission of the People's Republic of China (Edition 7). In general, patients diagnosed with COVID-19 pneumonia must also meet any of the following criteria: appears shortness of breath, respiratory rate (RR) ≥ 30 times/min; SPO2 ≤ 93% at rest; the ratio of partial oxygen pressure of arterial blood (PaO2) to oxygen absorption concentration (FiO2) ≤ 300mmHg (1mmHg=0.133KPa); pulmonary imaging showed the lesion progression ＞50% within 24-48 hours. All enrolled patients were given general support therapy, oxygen therapy, antiviral drugs, in combination with antibiotics and small doses of glucocorticoids if necessary, nutritional and organ function support. Patients in the berberine group (B group) were given berberine 0.3g tid orally or tube feed daily, while patients in the control group (C group) were given montmorilonite orally if they presence of diarrhea. The duration of the study intervention was 14 days and followed up to discharge. Investigators record general information about patients at admission, including age, gender, age, exposure history, time from onset of symptoms to hospital, APACHE II score, the presentation of X-ray, comorbidity, mechanical ventilation, fever or not,gastrointestinal symptoms. Investigators also evaluate the gastrointestinal function daily,including gastrointestinal symptoms (nausea, vomiting, abdominal pain, abdominal distension or diarrhoea), frequency of diarrhea, the characteristics of stool (Bristol scal). Peripheral blood are collected on day 1,3, 7 and 14 after admission to determine the level of interleukin-6 (IL-6), interleukin-1β (IL-1β), interleukin-10 (IL-10) and tumor necrosis factor (TNF-α). Laboratory tests are also performed to evaluate leucocyte, c-reactive protein (CRP), and procalcitonin (PCT) levels at the same time. Glutamate transaminase (ALT), glutamate transaminase (AST), urea nitrogen (Bun), creatinine, prothrombin time (PT), partially activated prothrombin time (APTT), and Sequential Organ Failure Assessment (SOFA) score are used to evaluate organ function on day 1,3, 7 and 14 after admission. Investigators also record the adverse events associated with the drug, length of stay and the prognosis at discharge. The patients are blinded to the group allocation. Two physicians are responsible for data processing, one is responsible for recording and collecting, and the other is responsible for checking, and they are all blind to the research.
Dates
| Last Verified: | 04/30/2020 |
| First Submitted: | 05/12/2020 |
| Estimated Enrollment Submitted: | 07/18/2020 |
| First Posted: | 07/20/2020 |
| Last Update Submitted: | 07/18/2020 |
| Last Update Posted: | 07/20/2020 |
| Actual Study Start Date: | 02/07/2020 |
| Estimated Primary Completion Date: | 04/17/2020 |
| Estimated Study Completion Date: | 04/22/2020 |
Condition or disease
Intervention/treatment
Drug: berberine group (B group)
Drug: control group (C group)
Phase
Arm Groups
| Arm | Intervention/treatment |
|---|---|
| Experimental: berberine group (B group) Patients in the B group were given berberine hydrochloride tables 0.3g tid orally or tube feed daily, until the 14th day of the study. Other treatments include general support therapy, oxygen therapy, antiviral drugs, in combination with antibiotics and small doses of glucocorticoids if necessary, nutritional and organ function support. | Drug: berberine group (B group) Patients in the intervention group received berberine daily, regardless of gastrointestinal symptoms.If the patient has a serious drug-related adverse event, the drug will be discontinued and the patient will be excluded from the study. |
| Sham Comparator: control group (C group) Patients in the C group were given montmorilonite orally if they presence of diarrhea. The other treatments were the same as in B group. | Drug: control group (C group) Patients in the control group were routinely not given special treatment.However, if the patient has diarrhea symptoms, montmorillonite powder should be given orally. |
Eligibility Criteria
| Ages Eligible for Study | 18 Years To 18 Years |
| Sexes Eligible for Study | All |
| Accepts Healthy Volunteers | Yes |
| Criteria | Inclusion Criteria: - Patients confirmed with COVID-19 and classified as severe Exclusion Criteria: - inflammatory bowel disease; - have other sources of infection; - death is anticipate within 72 hours; - participated in other clinical trials; - pregnant or lactating women; |
Outcome
Primary Outcome Measures
1. Changes in diarrhea frequency and Bristol Stool Scale [daily, from date of randomization until the date of discharge or date of death from any cause, assessed up to 2 weeks.]
Secondary Outcome Measures
1. IL-6 (ng/ml) [baseline (at admission), day 3,7 and14 after admission or until the date of discharge or date of death from any cause]
2. IL-10（ng/ml） [baseline (at admission), day 3,7 and14 after admission or until the date of discharge or date of death from any cause]
3. IL-1β (ng/ml) [baseline (at admission), day 3,7 and14 after admission or until the date of discharge or date of death from any cause]
4. TNF-α (pg/ml) [baseline (at admission), day 3,7 and14 after admission or until the date of discharge or date of death from any cause]
5. leukocyte count (10^9/l) [baseline (at admission), day 3,7 and14 after admission or until the date of discharge or date of death from any cause]
6. c reactive protein (mg/l) [baseline (at admission), day 3,7 and14 after admission or until the date of discharge or date of death from any cause]
7. procalcitonin (ng/ml) [baseline (at admission), day 3,7 and14 after admission or until the date of discharge or date of death from any cause]
Other Outcome Measures
1. Sequential Organ Failure Assessment (SOFA) score [baseline (at admission), day 3, 7 and 14 after admission or until the date of discharge or date of death from any cause]
