An Open-Label clinical study to evaluate efficacy and safety of Metronidazole Injection manufactured by Nirma Limited for the treatment of Lower Respiratory Tract Infections, Intra abdominal infections and other bacterial infections.

Title

An Open-Label clinical study to evaluate efficacy and safety of Metronidazole Injection manufactured by Nirma Limited for the treatment of Lower Respiratory Tract Infections, Intra abdominal infections and other bacterial infections.

|Objective

The objective of the study is to evaluate efficacy and safety of Metronidazole Injection 500 mg / 100 mL IV administration in patients with Lower Respiratory Tract Infections, Intra abdominal infections and other bacterial infections. that are proven or strongly suspected to be caused by bacteria.

|Study design

Open-Label study.

|Study

Population

Patients suffering from any of Lower Respiratory Tract Infection, Intra abdominal Infection and other bacterial infections that are proven or strongly suspected to be caused by bacteria will be recruited from the local population.

  |Sample Size

30 evaluable patients.

  |No. of centers

01 (One)

|Study treatment

By intravenous infusion, the recommended dose of Metronidazole I.V. for adults is 500 mg per dose given over approximately 20 minutes infusion, twice a day (every 12 hourly) for at least 05 to 07 days based on the condition of patients. Dosage can be adjusted according to the physical condition such as age and symptom of each individual, but should not exceed 4000 mg per dose.

|Key Inclusion

Criteria

·      Patient within 18 – 65 years of age ( both inclusive)

·      Women of child bearing age with a normal menstrual cycle and a negative pregnancy test.

·      Patient suffering from Intra-Abdominal infectionhad to have signs/ symptoms such as abdominal pain, tenderness etc. A case will be defined as an intra-abdominal abscess or peritoneal fluid culture that will be positive for enterococcus or an enterococcal bacteraemia in association with an intra-abdominal source of infection.

·      Patients suffering from lower respiratory tract infections ( LRTIs) had to have at least two of the following: fever (> 98.6 ° F) or hypothermia, cough with sputum, dyspnea, crackles, rales, pleuritic pain, dullness of percussion, and leukocytosis or leucopenia.

|Key Exclusion

Criteria

The patients will be excluded based on the following criteria :

1.       History of previous allergy to β-lactam antibiotics or history of seizure.

2.       History of consumption of any other antimicrobial agent within last 72 hours.

3.       New drug trial in the three previous months.

4.       History of severe cardiac, renal or haematological impairment.

5.       Patients with continuing history of alcohol and / or drug abuse.

6.       Increased hepatic or renal enzyme levels >3 times of the upper limit of the normal range.

7.       Patient with terminal malignancy or psychiatric illness.

8.       Pregnant or nursing woman.

|Assessments

Clinical Assessment (body temperature, blood pressure, respiratory rate, pulse rate, examination of cardiovascular system, respiratory system, central nervous system, gastrointestinal system etc.) including symptoms and signs of all patients should be performed throughout the medication period.

Laboratory assessments will includes routine haematology, bio-chemistry, serology test (HIV 1 and 2 antibodies, HBsAg, HCV) urine analysis profiles, electrocardiogram, chest X - ray (if required) will be performed at enrolment and after completion of therapy, except serology test.

Based on the patient’s clinical examination, specimens will be taken from sputum (for lower respiratory tract infection) or stool (for intra abdominal infection) for bacterial culture prior to initial treatment and during post therapy visit (if required).

If the culture test is found negative patient will be withdrawn from the study and/or alternative treatment would be provided to the patient. However patient may still be continued in the study, if the investigator is of the opinion that further participation of the patient may benefit him/her from the ongoing treatment.  The data of such patients will not be considered for statistical evaluation.

The patient withdrawn from the study due to negative culture test, will be replaced.

However if patient is dropped out due to adverse event, patient will not be replaced.

|Clinical Efficacy

The clinical efficacy will be classified as follows:

Cure – will be defined based on investigator’s discretion as following:

i)                    all the presenting symptoms and signs were resolved with respect to baseline characteristics

ii)                  the laboratory tests  like WBC count clinically not significant

iii)                absence of bacteria in urine microscopy and clinical procedures were normal

Marked improvement - will be defined as based on investigator’s discretion:

i)                 one abnormality in the signs and symptoms remained at treatment termination with respect to baseline characteristics

ii)               the laboratory tests  like WBC count clinically not significant

iii)             absence of bacteria in urine microscopy and clinical procedures were normal

Improvement – will be defined as based on investigator’s discretion:

i)                 atleast one abnormality in the signs and symptoms resolved and no abnormality worsened at treatment termination with respect to baseline characteristics

ii)               the laboratory tests  like WBC count clinically not significant

iii)             absence of bacteria in urine microscopy and clinical procedures were normal

Failure – clinical manifestation remained or were aggravated after 72 hours of treatment

Cure rate and efficacy rate will be determined.

|Safety Assessments

1)      Safety assessments will be classified into five categories as definitely, probably, possibly and possibly or definitely drug unrelated.

2)      SGOT and SGPT values at baseline and the end of treatment will be compared for safety assessment

|Outcome

1. Efficacy rate:

The proportion of the ‘cure’ and ‘marked improvement’ categories will be employed to calculate the overall efficacy rate.

2. Improvement in scores in signs and symptoms with respect to baseline characteristics, of LRTI, Intra abdominal infection and other bacterial infections.

3. To evaluate safety of the study drug.

|Statistical analysis

Statistical analysis will be evaluated with statistical analysis plan usingSAS version 9.2 software or higher.