Home » Trials » SLCTR/2018/016


The efficacy and safety of N-acetylcysteine in patients with acute kidney injury complicating leptospirosis – A randomized controlled clinical trial -

SLCTR Registration Number

SLCTR/2018/016


Date of Registration

08 Jun 2018

The date of last modification

Jun 08, 2018



Application Summary


Scientific Title of Trial

The efficacy and safety of N-acetylcysteine in patients with acute kidney injury complicating leptospirosis – A randomized controlled clinical trial


Public Title of Trial

‘Effectiveness and safety of the use of N-acetylcysteine in patients with kidney failure in leptospirosis’


Disease of Health Condition(s) Studied

Leptospirosis, Acute kidney injury


Scientific Acronym

L-NAC Trial (Leptospirosis N-acetylcysteine Trial)


Public Acronym

L-NAC Trial (Leptospirosis N-acetylcysteine Trial)


Brief title

None


Universal Trail Number

U1111-1206-6133


Any other number(s) assigned to the trial and issuing authority

EC 17-117; Ethics Review Committee, Faculty of Medicine, University of Colombo and NRC 15-069 by National Research Council of Sri Lanka


Trial Details


What is the research question being addressed?

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


Type of study

Interventional


Study design

Allocation

Randomized controlled trial


Masking

Double blinded


Control

Placebo


Assignment

Parallel


Purpose

Treatment


Intervention(s) planned

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.


Inclusion criteria

  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).

Exclusion 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


Primary outcome(s)

  1. Renal replacement therapy free survival at 30 days

  2. Mortality at 30 days


Primary outcome(s) - Time of assessment(s)

30 days


Secondary outcome

  1. Improvement of platelet count >100,000

  2. Length of hospital stay

  3. Improvement in parameters of oxidative stress and increase in antioxidant capacity – nitric oxide (NO) activity (with the surrogate combination assay of nitrates and nitrites (NOx), measurement of protein-carbonyl, antioxidant capacity (AOC) and lipid peroxidase. The level of improvement is noted at 25% from baseline measured values

  4. Safety outcomes: Development of anaphylaxis with NAC and the following manifestations: angioedema, bronchospasm respiratory distress, hypotension.


Secondary outcome(s) - Time of assessment(s)

  1. Improvement of platelet count >100,000

  2. Length of hospital stay

  3. Improvement in parameters of oxidative stress and increase in antioxidant capacity – nitric oxide (NO) activity (with the surrogate combination assay of nitrates and nitrites (NOx), measurement of protein-carbonyl, antioxidant capacity (AOC) and lipid peroxidase. The level of improvement is noted at 25% from baseline measured values

  4. Safety outcomes: Development of anaphylaxis with NAC and the following manifestations: angioedema, bronchospasm respiratory distress, hypotension.



Target number/sample size

120 (60 in each arm)


Countries of recruitment

Sri Lanka


Anticipated start date

2018-07-01


Anticipated end date

2019-07-01


Recruitment status

Pending


State of ethics review approval

Approved by the Ethics Review Committee, Faculty of Medicine, University of Colombo on 16th November 2017 ( EC 17-117)


Funding source

National Research Council, Sri Lanka (grant no. 15-069)



Contact & Sponsor Information


Contact person for Scientific Queries/Principal Investigator

Senaka Rajapakse
Professor in Clinical Medicine and Consultant Physician
Department of Clinical Medicine, Faculty of Medicine, University of Colombo, 225, Kynsey Road, Colombo 08, Sri Lanka
+94112695300


senaka@med.cmb.ac.lk

Contact Person for Public Queries

Senaka Rajapakse
Professor in Clinical Medicine and Consultant Physician
Department of Clinical Medicine, Faculty of Medicine, University of Colombo, 225, Kynsey Road, Colombo 08, Sri Lanka
+94112695300


senaka@med.cmb.ac.lk


Primary study sponsor/organization

National Research Council of Sri Lanka

Ground Floor, Sri Lanka Institute of Architects Building, 120/07, Vidya Mawatha Colombo 07, Sri Lanka
+94 011 2675176
+94 11 2675136

http://www.nrc.gov.lk/

Secondary study sponsor (If any)

None