Is N-acetylcysteine effective and safe in patients with leptospirosis complicated by acute kidney injury?

The study will be carried out at the University Medical Unit, National Hospital of Sri Lanka, Colombo, Sri Lanka.

Simple randomization will be used to allocate participants into two groups (1:1 allocation protocol), namely the treatment arm and the placebo arm using a computer generated randomization system. The computer generated numbers will be printed and sealed in envelopes by an independent person not involved in the trial (allocation concealment).

Intervention: N-acetylcysteine (NAC)

The intervention arm will receive intravenous NAC. The dosing schedule for NAC will be modified from the protocol used in clinical trials investigating the use of the agent in the prevention of contrast induced nephropathy. Patients in the treatment arm will receive a bolus injection of 1200mg of NAC diluted in 15 ml of normal saline. This dose will be repeated at 12 hours, 24 hours, 36 hours and 48 hours. The cumulative dose of NAC utilized will be 6000mg.

Placebo: 0.9% saline

The control arm will receive the identical volume of 0.9% saline (15ml) administered as a bolus and repeated at 12 hours, 24 hours, 36 hours and 48 hours.

All other management will be provided equally to all participants according to standard guidelines and unit protocols. The National Guidelines on Management of Leptospirosis, published by the Epidemiology Unit, Ministry of Health, Sri Lanka (http://www.epid.gov.lk/web/images/pdf/Publication/leptospirosis/lepto_ national_guidelines.pdf) will be used as the management guideline. ).

The participants, investigators who recruit the patient, data collectors, health care providers including physicians and nursing officers who administer the infusion, outcome adjudicators and data analysts will be blinded. An independent investigator will maintain the computer randomized number table and another independent investigator will prepare the solutions of NAC and placebo saline for infusion and provide according to the randomization number directly to the nursing staff for administration.

1. Male and female subjects aged 18 years and above
2. Confirmed diagnosis of leptospirosis as determined by Leptospirosis Immunochromatography test and Leptospirosis Microscopic Agglutination Test
3. Acute kidney injury, defined based on Kidney Disease Improving Global Outcomes criteria: (KDIGO criteria).

1. Patients with clinical or serological evidence of co-infection with dengue or Hanta virus
2. Patients on nitrates and other antioxidant medication including vitamin E supplementation
3. Superadded pulmonary hemorrhages as a complication of leptospirosis
4. Patients with acute liver dysfunction defined as: clinical evidence of encephalopathy and or evidence of coagulopathy with INR>1.5 with significant jaundice and a total serum bilirubin level of >100 µmol/L
5. Patients in cardiogenic or septic shock as a complication of leptospirosis
6. Pregnancy – All female patients will undergo urinary beta HcG testing prior to inclusion