Anisodamine Critically Ill SeptIc Shock

NCT ID: NCT02442440

Last Updated: 2021-09-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 355 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-04-30
• Study Completion Date: 2020-10-01

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.

Conditions

Septic Shock

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

anisodamine group

administration of the drug

Group Type: EXPERIMENTAL

anisodamine

Intervention Type: DRUG

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.

control group

these arm do not use anisodamine, other resuscitation protocol is as usual.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

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.

Intervention Type: DRUG

Other Intervention Names

654-2

Eligibility Criteria

Inclusion Criteria

• patients with septic shock

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.

• Minimum Eligible Age: 15 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Jinhua Central Hospital

OTHER

Sponsor Role: lead

Responsible Party

Zhongheng Zhang

Dr.

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

kun chen, MSc

Role: STUDY_DIRECTOR

Jinhua Municipal Central Hospital

Locations

Huizhou first hospital

Huizhou, Guangdong, China

Union Hospital, Tongji medical collegue, Huazhong university of Science and Technology

Wuhan, Hubei, China

the First Affiliated Hospital of Nanjing Medical University

Nanjing, Jiangsu, China

affiliated hospital, Jiangsu University

Zhenjiang, 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 Municipality, China

Peace hospital of Changzhi medical college

Changzhi, Shanxi, China

The first People's hospital of Yongkang

Guli, Zhejiang, China

Zhejiang Hospital

Hangzhou, Zhejiang, China

Sir Run Run Shaw hospital

Hangzhou, Zhejiang, China

Sir Run Run Shaw 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

Taizhou hospital of Zhejiang province

Taizhou, Zhejiang, China

Countries

China

References

Yu Y, Zhu C, Hong Y, Chen L, Huang Z, Zhou J, Tian X, Liu D, Ren B, Zhang C, Hu C, Wang X, Yin R, Gao Y, Zhang Z. Effectiveness of anisodamine for the treatment of critically ill patients with septic shock: a multicentre randomized controlled trial. Crit Care. 2021 Sep 27;25(1):349. doi: 10.1186/s13054-021-03774-4.

Reference Type: DERIVED

PMID: 34579741 (View on PubMed)

Zheng Y, Li Y, Liu X, Zhang R, Wang Z, Sun H, Liu S. A phase III, multicenter randomized controlled trial of neo-adjuvant chemotherapy paclitaxel plus cisplatin versus surgery alone for stage IIA-IIIB esophageal squamous cell carcinoma. J Thorac Dis. 2017 Jan;9(1):200-204. doi: 10.21037/jtd.2017.01.44.

Reference Type: DERIVED

PMID: 28203424 (View on PubMed)

Zhang Z, Zhou J, Shang Y, Wang X, Yin R, Zhu Z, Chen W, Tian X, Yu Y, Zuo X, Chen K, Ji X, Ni H; Anisodamine Critically Ill SeptIc Shock (ACIdoSIS) study group. Effectiveness of anisodamine for the treatment of critically ill patients with septic shock (ACIdoSIS study): study protocol for randomized controlled trial. Ann Transl Med. 2015 Oct;3(17):246. doi: 10.3978/j.issn.2305-5839.2015.10.03.

Reference Type: DERIVED

PMID: 26605292 (View on PubMed)

Other Identifiers

2015-013

Identifier Type: -

Identifier Source: org_study_id