Safety and Efficacy of the Tong-Fu-Xing-Shen Herbal Formula for Stroke-Associated Pneumonia
Safety and Efficacy of the Tong-Fu-Xing-Shen Herbal Formula for Stroke-Associated Pneumonia
Stroke-associated pneumonia (SAP) is the major complication of acute intracerebral
 haemorrhage (AICH), leads to poor clinical outcomes and increases the financial burden on the
 medical system. Prophylactic antibiotics do not reduce the mortality rate of SAP. The
 Tong-Fu-Xing-Shen herbal formula (TFXS) was shown to be effective for the prevention and
 treatment SAP in a previous clinical trial. To clarify whether TFXS is effective and safe for
 the treatment of SAP and affects the immunological mechanism of the "brain-gut-lung" pathway
 of SAP, the investigators designed this study.
This is a multicentre, randomized, double-blind, placebo-controlled clinical trial. A total
 of 218 patients will be recruited and randomly assigned to the experimental group (EG) or the
 control group (CG) in a 1:1 ratio. The treatment course will be 10-12 consecutive days, with
 a 90±7-day follow-up. The primary outcome is the all-cause mortality rate and the mortality
 of pneumonia at the 90±7-day follow-up. Secondary outcomes include changes in the gut
 microbiota; changes in the NIHSS score, BI index, mRS score, and Stroke-Specific Quality of
 Life scale (SS-QOL) score; and so on.
Inclusion criteria

 For inclusion, participants will need to fulfil all the following criteria:

 1. A diagnosis of intracerebral haemorrhage according to 2019 Chinese guidelines for the
 diagnosis and treatment of acute intracerebral haemorrhage [9], with a CT scan of the
 brain confirming acute intracerebral haemorrhage;

 2. Age between 18 and 85;

 3. A diagnosis of SAP according to the modified CDC standard [10];

 4. Within 7 days after stroke onset; and

 5. Willingness to participate and to sign the informed consent form.

 Exclusion criteria

 Participants with any of the following conditions will be excluded:

 1. Cerebral haemorrhage is confirmed by examination to be caused by a brain tumour, brain
 trauma, blood disease, cerebrovascular malformation (a congenital abnormality) or
 aneurysm;

 2. Cerebral herniation;

 3. A GCS score <7;

 4. Any antibiotic treatment within 4 weeks before the start of the study;

 5. Pulmonary tuberculosis, pulmonary oedema, pulmonary embolism, noninfectious pulmonary
 oedema or respiratory circulation failure;

 6. Liver or kidney function parameters (such as alanine aminotransferase [ALT], aspartate
 aminotransferase [AST] and creatinine [Cre]) 3 times higher than the upper limit of
 normal;

 7. A clear history of gastrointestinal diseases, such as gastrointestinal tumours and
 inflammatory bowel disease, or a gastrointestinal bleeding period within 3 months;

 8. Immune-related diseases, such as SLE, rheumatoid arthritis, and Sjogren's syndrome, or
 receiving immunotherapy for other diseases; and

 9. Unsuitable for the trial as decided by the researchers.