N-acetylcysteine as an adjuvant therapy in acute aluminum phosphide poisoning: A randomized clinical trial

To assess the safety and efficacy of N-acetyl cysteine as adjuvant therapy in patients with acute aluminum phosphide poisoning

Two arm parallel group, single-blind, randomized controlled trial of 48 patients, enrolled between September 2020 and February 2021.

The trial will be conducted at "Menoufia Poison Control and Dependence Center", which is a part of 'Menoufia University Hospital" located at Shebin Elkom city, Egypt. Participants and data analyzers will be blinded by making a letter for each medication used and masking the names of the medication and the intervention groups.

We will include patients with history of aluminum phosphide tablet ingestion and having clinical manifestations besides reliable identification of the compound (from the container or silver nitrate test) We will exclude patients less than 12-years-old, pregnant/lactating women, patients with chronic diseases, and those who dissolved the phosphide tablet in water before ingestion 5. Ingestion of air-exposed tablets 6. Patients refusal to participate

Control group: Patients will receive the standard treatment [patient resuscitation, gastric decontamination, and supportive treatment (sodium bicarbonate, inotropes, intravenous fluids, electrolytes, intubation, mechanical ventilation, and anti-arrhythmic agents as indicated)]. Intervention group: Patients will receive the standard treatment. In addition, N-acetyl cysteine (produced by Rotabiogen for Pharmaceuticals Invest for Arabcomed-Egypt) will be administered as 150 mg/kg (in 200 ml 5% dextrose) by intravenous infusion over 1 hour, followed by 50 mg/kg (in 500 ml 5% dextrose) over 4 hours, then 100 mg/kg (in 500 ml 5% dextrose) over 16 hours.

All-cause mortality during hospital admission, Duration of ventilation, Duration of hospitalization

We used the sealed, opaque sequentially numbered envelopes method for randomization and allocation concealment of patients included in this trial as described by Doig and Simpson (2005). We used 48 identical, opaque, letter-sized envelopes. We used 2 rolls of household aluminum cooking foil that we cut into 48 sheets (of the same width as and twice the height of the envelope). We prepared 48 envelope-sized sheets of white paper and 48 envelope-sized sheets of single sided carbon paper. We wrote “Treatment A” on 24 paper sheets and “Treatment B” on the other 24 sheets. To prepare 24 Treatment A envelops, we selected one envelope-sized sheet of of Treatment A and placed one sheet of carbon paper on top of the Treatment A allocation paper with the carbon side facing the paper, then we put both papers inside a foil wrapper. Then, the completed insert was placed into a blank envelope with the carbon paper closest to the front of the envelope. Finally, the envelop was sealed and we signed across the seal. We completed all the 24 Treatment A envelops the same way. We prepared 24 Treatment B envelops the same way as Treatment A envelops. Both sets of envelops were combined and we shuffled them thoroughly. Then, using a pen we marked a number on the front of each envelope sequentially from 1 to 48. The carbon paper inside the envelope transferred this number to the allocation paper inside. Finally, we placed these envelopes into a plastic container, in numerical order, ready for use. Doig GS, Simpson F. Randomization and allocation concealment: a practical guide for researchers. J Crit Care 2005;20:187–93.

Participants & data analyzers will be blinded. We will achieve this by making a letter for each medication used and masking the name of the medication & masking the intervention groups (data will be presented to data analyzers as groups A and B.

We plan to share all IPD that underlie results

Data will become available 12 months and ending 36 months following article publication

Researchers from academic institutions whose proposal for the use of data has been approved by an independent review committee identified for this purpose

For IPD meta-analysis

Data will be obtainable from the PI

A proposal for the use of data to be submitted to the PI, then evaluated by an independent review committee identified for this purpose