UMIN-ICDS Clinical Trial

Public title

Intravenous N-acetylcysteine as adjunctive therapy for acute aluminum phosphide poisoning: an updated systematic review of randomized controlled trials

Acronym

AlP-NAC SR and MA

Scientific Title

Efficacy and safety of intravenous N-acetylcysteine in acute aluminum phosphide poisoning: an updated systematic review and meta-analysis of randomized controlled trials

Scientific Title:Acronym

AlP-NAC SR and MA

Region

Japan	Asia(except Japan)	North America
South America	Australia	Europe
Africa

Condition

Acute aluminum phosphide poisoning

Classification by specialty

Emergency medicine

Intensive care medicine

Classification by malignancy

Others

Genomic information

NO

Narrative objectives1

To evaluate whether adding intravenous N-acetylcysteine to standard care reduces in-hospital or up-to-30-day all-cause mortality in patients with acute aluminum phosphide poisoning compared with the same standard care alone or the same standard care plus placebo. Secondary objectives are to assess intubation or invasive mechanical ventilation, vasopressor use, shock improvement, and serious adverse events.

Basic objectives2

Safety,Efficacy

Basic objectives -Others

Trial characteristics_1

Trial characteristics_2

Developmental phase

Not applicable

Primary outcomes

All-cause mortality. One time point per trial will be selected in the following order: day 30, day 28, death during the index hospitalization, and the longest reported time point within 30 days. In-hospital mortality will remain eligible when hospitalization exceeds 30 days; sensitivity analyses will separately use only 28- to 30-day mortality and only in-hospital mortality.

Key secondary outcomes

1) Endotracheal intubation or invasive mechanical ventilation after randomization through discharge or day 30
2) any vasopressor use over the same period, with new initiation among baseline non-users analyzed separately and not pooled with dose or duration
3) trial-defined binary shock improvement or resolution among participants in shock at randomization, prioritized at 24 hours, 48 hours, and the nearest acute time point; post-treatment blood pressure or MAP alone will not be dichotomized
4) participants with at least one serious adverse event through discharge or day 30.

Study type

Others,meta-analysis etc

Basic design

Randomization

Randomization unit

Blinding

Control

Stratification

Dynamic allocation

Institution consideration

Blocking

Concealment

No. of arms

Purpose of intervention

Type of intervention

Interventions/Control_1

Interventions/Control_2

Interventions/Control_3

Interventions/Control_4

Interventions/Control_5

Interventions/Control_6

Interventions/Control_7

Interventions/Control_8

Interventions/Control_9

Interventions/Control_10

Age-lower limit

Not applicable

Age-upper limit

Not applicable

Gender

Male and Female

Key inclusion criteria

Individual- or cluster-randomized controlled trials enrolling patients with acute aluminum phosphide poisoning. The intervention must be intravenous N-acetylcysteine added to standard care, and the comparator must be the same standard care alone or the same standard care plus placebo. Arm-level data for aluminum phosphide poisoning must be separable. No restriction will be placed on age, sex, severity, country, language, or publication status.

Key exclusion criteria

Studies of zinc phosphide or other poisons only, or mixed-poison studies without separable arm-level aluminum phosphide data; studies using non-intravenous N-acetylcysteine; studies in which any planned non-N-acetylcysteine cointervention differs between groups; non-randomized or quasi-randomized studies using predictable methods such as alternation, record or patient numbers, birth dates, or admission dates; and duplicate reports of the same trial, which will be linked as one trial family.

Target sample size

200

Name of lead principal investigator

1st name	Kazuma
Middle name
Last name	Yamakawa

Organization

Osaka Medical and Pharmaceutical University

Division name

Department of Emergency and Critical Care Medicine, Faculty of Medicine

Zip code

569-8686

Address

2-7 Daigaku-machi, Takatsuki, Osaka 569-8686, Japan

TEL

072-683-1221

Email

kazuma.yamakawa@ompu.ac.jp

Name of contact person

1st name	Kazuma
Middle name
Last name	Yamakawa

Organization

Osaka Medical and Pharmaceutical University

Division name

Department of Emergency and Critical Care Medicine, Faculty of Medicine

Zip code

569-8686

Address

2-7 Daigaku-machi, Takatsuki, Osaka 569-8686, Japan

TEL

072-683-1221

Homepage URL

Email

kazuma.yamakawa@ompu.ac.jp

Institute

Department of Emergency and Critical Care Medicine, Faculty of Medicine, Osaka Medical and Pharmaceutical University

Institute

Department

Personal name

Organization

Self funding

Organization

Division

Category of Funding Organization

Self funding

Nationality of Funding Organization

Co-sponsor

Name of secondary funder(s)

Organization

Not applicable

Address

Not applicable

Tel

Not applicable

Email

Not applicable

Secondary IDs

NO

Study ID_1

Org. issuing International ID_1

Study ID_2

Org. issuing International ID_2

IND to MHLW

Institutions

Date of disclosure of the study information

2026

Year

09

Month

01

Day

URL releasing protocol

Publication of results

Unpublished

URL related to results and publications

Number of participants that the trial has enrolled

Results

Results date posted

Results Delayed

Results Delay Reason

Date of the first journal publication of results

Baseline Characteristics

Participant flow

Adverse events

Outcome measures

Plan to share IPD

IPD sharing Plan description

No

Recruitment status

Preinitiation

Date of protocol fixation

2026

Year

09

Month

01

Day

Date of IRB

Anticipated trial start date

2026

Year

09

Month

01

Day

Last follow-up date

2026

Year

10

Month

31

Day

Date of closure to data entry

Date trial data considered complete

Date analysis concluded

2027

Year

03

Month

31

Day

Other related information

This is an updated RCT-only systematic review and meta-analysis. Preliminary candidates are Bhalla 2017, El-Ebiary 2017, Emam 2020, and Abd El-Khalek 2025 (four trials; 236 participants); final numbers will follow the updated search. Tehrani 2013 is a quasi-randomized study based on patient-file numbers, and Ashraf 2022 used oral NAC; both are exclusion candidates.
MEDLINE, Embase, CENTRAL will be searched from inception without language restrictions, with citation tracking and author contact. Studies described as randomized but lacking sequence-generation details will be provisionally eligible, queried, and assessed in RoB 2 unless an explicit quasi-random method is identified. Discrepancies across registries and reports will be linked and documented by trial family. Two human reviewers will independently make final decisions on selection, extraction, RoB 2, and GRADE. Mortality will use risk ratios and a REML random-effects model; Hartung-Knapp-Sidik-Jonkman type intervals will be used when k>2 and tau-squared>0, otherwise Wald intervals, with a common-effect sensitivity analysis. Trials will not be removed solely for heterogeneity or significance. SAE counts require explicit definitions and systematic arm-level collection; statements such as 'no adverse events' will not be treated as zero.
Clarion Evidence Studio will manage and perform all stages. AI will not count as a reviewer; source anchors, rationales, changes, and audit exports will be retained.

Registered date

2026

Year

08

Month

26

Day

Last modified on

2026

Year

08

Month

26

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000071784