Anisodamine Critically Ill SeptIc Shock

Septic Shock Clinical Trial

— ACIdoSIS  

Official title:

Effectiveness of Anisodamine for the Treatment of Critically Ill Patients With Septic Shock: a Randomized Controlled Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02442440
• Other study ID #: 2015-013
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: April 2015
• Est. completion date: October 1, 2020

Study information

• Verified date: September 2021
• Source: Jinhua Central Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Anisodamine has been widely used in China for its pharmacological effect on improving microcirculation during shock. It has been reported that anisodamine is effective in reducing mortality rate in children with meningitis. however, its effectiveness in patients with septic shock has not been systematically investigated. The aim of the study is to investigate the effectiveness of anisodamine in the treatment of patients with septic shock.

Description:

Septic shock is an important contributor of mortality in the intensive care unit (ICU). The crude mortality is reported to be from 30% to 65% (1-5). Although there are significant advances in the management of septic shock in recent decades, the mortality rate was only marginally reduced. For example, the CUB-Réa Network study reported that the mortality rate of septic shock declined from 62.1% in 1993 to 55.9% in 2000 (6). The well-known Surviving Sepsis Campaign has also made every effort to reduce mortality rate of severe sepsis and septic shock. The organization recommended bundled strategies including early goal directed therapy (EGDT) for the management of septic shock (7,8). Although EGDT was once the mainstay therapy of septic shock, its efficacy has been questioned by recent several large randomized controlled trials (9,10). Therefore, the treatment of septic shock is still a global challenge and there is no well-established intervention that can reduce its mortality.

Anisodamine is an active agent isolated from a Chinese herb medicine. Both experimental and clinical studies have shown some potential beneficial effects of anisodamine in improving outcomes of shock (11-13). It was reported that anisodamine could reduce the mortality rate of fulminant epidemic meningitis from 66.9% to 12.4% (14). The efficacy of anisodamine might be mediated via the inhibition of thromboxane synthesis, granulocyte and platelet aggregation (15). Although anisodamine has been widely used in the treatment of septic shock in mainland China, there is no solid evidence from well designed clinical trials to support its efficacy. The aim of the study is to investigate the effectiveness of anisodamine in the treatment of critically ill patients with septic shock.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 355
• Est. completion date: October 1, 2020
• Est. primary completion date: October 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 15 Years and older

Eligibility

Inclusion Criteria:

• patients with septic shock

Inclusion criteria included patients with sepsis plus use of vasopressors. Systemic inflammatory response syndrome (SIRS) is defined as meeting at least one of the following 3 criteria for a systemic inflammatory response. One of the SIRS criteria must be either the WBC criteria (a) or the body temperature criteria (b):

1. White blood cell count >12,000 or <4,000 or >10% band forms

2. Body temperature >38oC (any route) or <36oC (accepting core temperatures only; indwelling catheter, esophageal, rectal)

3. Heart rate (> 90 beats/min) or receiving medications that slow heart rate or paced rhythm.

Suspected or documented infection included the following sites: thorax, urinary tract, abdomen, skin, sinuses, central venous catheters, and bacterial meningitis.

Septic shock was defined as sustained arterial hypotension with systolic blood pressure (SBP) < 90 mm Hg, mean arterial pressure (MAP) < 70 mm Hg, or an SBP decrease > 40 mm Hg, despite adequate fluid resuscitation. To ease clinical screening process, we defined septic shock as the requirement of vasopressors despite adequate fluid resuscitation. Vasopressors include norepinephrine, epinephrine, phenylephrine and dopamine>5mcg/kg/min.

Patients with following conditions will be excluded:

1. Age<15 years old

2. Moribund (expected to die within 24 hours)

3. Stay in ICU for more than 24 hours

4. Contraindications to anisodamine: elevated intracranial pressure, acute phase of intracranial hemorrhage, glaucoma, untreated bowel obstruction (surgically treated obstruction is not contraindicated), enlargement of prostate without urinary catheterization.

Related Conditions & MeSH terms

• Septic Shock
• Shock
• Shock, Septic

Intervention

Drug:
• anisodamine
Anisodamine will be given first as bolus of 10 mg, followed by 0.1-0.5mg/kg/hr. The adjustment of pump infusion rate is largely at the discretion of treating physician, with the aim of improving microcirculation and limit the side effect to a minimum. For example, if serum lactate continues to elevate, the infusion rate can be increased. Discontinuation on severe side effect or recovery of shock (normalized lactate, weaned from vasopressor) or death.

Locations

Country	Name	City	State
China	Binzhou People's hospital of Shandong province	Binzhou	Shandong
China	Peace hospital of Changzhi medical college	Changzhi	Shanxi
China	Sir Run Run Shaw hospital	Hangzhou	Zhejiang
China	Sir Run Run Shaw hospital	Hangzhou	Zhejiang
China	Zhejiang Hospital	Hangzhou	Zhejiang
China	Huizhou first hospital	Huizhou	Guangdong
China	Jinhua Municipal Central Hospital	Jinhua	Zhejiang
China	Department of critical care medicine, The central hospital of Lishui City	Lishui	Zhejiang
China	the First Affiliated Hospital of Nanjing Medical University	Nanjing	Jiangsu
China	Beilun People's hospital; The first affiliated hospital of Zhejiang university (Beilun Branch)	Ningbo	Zhejiang
China	department of critical care medicine, Ren Ji Hospital, School of medicine, Shanghai Jiao Tong University	Shanghai	Shanghai
China	Taizhou hospital of Zhejiang province	Taizhou	Zhejiang
China	Union Hospital, Tongji medical collegue, Huazhong university of Science and Technology	Wuhan	Hubei
China	The first People's hospital of Yongkang	Yongkang	Zhejiang
China	affiliated hospital, Jiangsu University	Zhenjiang	Jiangsu

Sponsors (1)

Lead Sponsor	Collaborator
Jinhua Central Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	hospital mortality	the outcome will be assessed by using proportion of patients died, and relative risk will be reported.	from ICU admission to hospital discharge (participants will be followed for the duration of hospital stay, an expected average of 28 days)
Secondary	lactate levels	the value was measured in mmol/l, and they will be compared between both arms.	from ICU admission to hospital discharge (participants will be followed for the duration of hospital stay, an expected average of 28 days)