Anisodamine Critically Ill SeptIc Shock

Phase 1

Completed

• Conditions: Septic Shock
• Interventions: Drug: anisodamine

• Registration Number: NCT02442440
• Lead Sponsor: Jinhua Central Hospital

Brief 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.

Detailed 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.

Study Timeline

• Study Start: 2015-04
• Study First Submitted: 2015-04-30
• Study First Submitted QC: 2015-05-12
• Study First Posted: 2015-05-13
• Primary Completion: 2020-10
• Study Completion: 2020-10-01
• Status Verified: 2021-09
• Last Update Submitted: 2021-09-23
• Last Update Posted: 2021-09-29

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 355

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.

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
anisodamine group	anisodamine	administration of the drug

Primary Outcome Measures

Name	Time	Method
hospital mortality	from ICU admission to hospital discharge (participants will be followed for the duration of hospital stay, an expected average of 28 days)	the outcome will be assessed by using proportion of patients died, and relative risk will be reported.

Secondary Outcome Measures

Name	Time	Method
lactate levels	from ICU admission to hospital discharge (participants will be followed for the duration of hospital stay, an expected average of 28 days)	the value was measured in mmol/l, and they will be compared between both arms.

Trial Locations

Locations (14)

Huizhou first hospital; 🇨🇳 Huizhou, Guangdong, China

Union Hospital, Tongji medical collegue, Huazhong university of Science and Technology; 🇨🇳 Wuhan, Hubei, China

affiliated hospital, Jiangsu University; 🇨🇳 Zhenjiang, Jiangsu, China

the First Affiliated Hospital of Nanjing Medical University; 🇨🇳 Nanjing, Jiangsu, China

Binzhou People's hospital of Shandong province; 🇨🇳 Binzhou, Shandong, China

department of critical care medicine, Ren Ji Hospital, School of medicine, Shanghai Jiao Tong University; 🇨🇳 Shanghai, Shanghai, China

Peace hospital of Changzhi medical college; 🇨🇳 Changzhi, Shanxi, China

Sir Run Run Shaw hospital; 🇨🇳 Hangzhou, Zhejiang, China

Zhejiang Hospital; 🇨🇳 Hangzhou, Zhejiang, China

Jinhua Municipal Central Hospital; 🇨🇳 Jinhua, Zhejiang, China

Department of critical care medicine, The central hospital of Lishui City; 🇨🇳 Lishui, Zhejiang, China

Beilun People's hospital; The first affiliated hospital of Zhejiang university (Beilun Branch); 🇨🇳 Ningbo, Zhejiang, China

The first People's hospital of Yongkang; 🇨🇳 Yongkang, Zhejiang, China

Taizhou hospital of Zhejiang province; 🇨🇳 Taizhou, Zhejiang, China