A clinical trial to evaluate the efficacy and safety of Rifamycin SV-MMX® compared to Ciprofloxacin in the treatment of acute infectious diarrhoea in travellers
A randomised, double-blind, double-dummy, multi-centre, comparative parallel-group study to evaluate the efficacy and safety of oral daily Rifamycin SV-MMX® 400 mg b.i.d. vs. Ciprofloxacin 500 mg b.i.d. in the treatment of acute infectious diarrhoea in travellers
Acronym ERASE
PAREXEL International Clinical Research Private Limited
Address
PAREXEL International Clinical Research Private Limited
Plot # 180, 3rd Floor, MFAR Silverline Tech Park, EPIP II Phase, Whitefield, Bangalore – 560066, Karnataka, India.
Patients who meet all of the following criteria can be enrolled into the study:
1. Signed informed consent,
2. Men or women between 18 and 85 years of age
3. History of arriving from their country of residence in the industrialized part of the world within the past 4 weeks
4. Presenting with acute infectious diarrhoea (defined as at least 3 unformed, watery or soft, stools accompanied by symptoms within 24 hours preceding randomisation with duration of illness ≤ 72 hours) and able to provide an unformed stool sample during screening (and the latter can be the third unformed stool passed by the patient in the 24 hours prior to randomization). The bacterial origin of diarrhoea will be examined “a posteriori†by stool microbiology sampling at the time of screening,
5. Presence of one or more signs or symptoms of enteric infection (moderate to severe gas/flatulence, nausea, vomiting, abdominal cramps or pain, rectal tenesm, fecal urgency),
6. Women of child-bearing potential have to apply during the entire duration of the study a highly effective method of birth control, which is defined as those which result in a low failure rate (i.e., less than 1% per year) when used constantly and correctly such as implants, injectables, combined oral contraceptive method, some IUDs, sexual abstinence or vasectomised partner. Note: The oral contraceptive method is ineffective in presence of diarrhoea and hormonal contraceptives could be inactivated in the presence of CYP inducers, such as Rifamycin SV. The investigator is responsible for determining an adequate method for birth control which the patient must agree to use.
ExclusionCriteria
Details
Patients who meet one of the following criteria are not allowed to be enrolled into the study:
1. US-American, Canadian, Australian and Indian (insurance, administrative and epidemiological reasons),
2. Residency in any country with a high incidence rate of traveller’s diarrhoea within the past six months
3. Fever (defined as a body (oral) temperature >100.4°F or 38.0°C; antipyretic medication should not be administered in the 6 hours prior to this assessment)
4. Known or suspected infection with non-bacterial pathogen,
5. Presence of diarrhoea of >72 hours duration,
6. Presence of grossly bloody stool,
7. Presence of moderate or severe dehydration (i.e. symptoms of hypovolemia such as orthostatic hypotension, dizziness or wrinkling of skin),
8. History of inflammatory bowel disease (IBD) and celiac disease,
9. Greater than two doses of an anti-diarrhoeal medication (e. g., antimotility, absorbent or antisecretory) within 24 hours before randomisation,
10. Receiving antibacterial drug with expected activity against gram negative bacterial pathogens (i. e., trimethoprim-sulfamethoxazole, fluoroquinolone, azithromycin or rifaximin) within 7 days prior to enrolment,
11. History or clinical evidence of severe impairment of liver and renal function,
12. Known intolerance/hypersensitivity/resistance to study drugs or drugs of similar chemical structure or pharmacological profile, or to any of the other constituents of the study drugs,
13. Doubt about the patient’s cooperation, e.g., because of addiction to alcohol or drugs, mental illness, travel schedule,
14. Females, with existing or intended pregnancy or breast-feeding, or not using adequate birth control,
15. Participation in another clinical trial within the last 30 days, simultaneous participation in another clinical trial, or previous participation in this trial,
16. Treatment with tizanidine,
17. History of tendon disease / disorder related to quinolone treatment,
18. History or clinical evidence of central nervous disorders which may be disposed to seizures,
19. Risk for torsades de pointes arrhythmia,
20. History or clinical evidence of gastrointestinal obstructions, perforations in the gastrointestinal tract, or severe intestinal ulcerative lesions.
Time to last unformed stool (TLUS)
Defined as the interval in hours between the first dose of study drug and the last unformed stool passed, after which clinical cure was declared.
Subjects who meet the criteria for clinical cure immediately after the start of the study and prior to passing any unformed stools are defined as having a TLUS of 0 hours.
Patients who terminated the study early due to treatment failure will have a censored TLUS of 120 hours.
A randomised, double-blind, double-dummy, multi-centre, comparative parallel-group study to evaluate the efficacy and safety of oral daily Rifamycin SV-MMXR 400 mg b.i.d. vs. Ciprofloxacin 500 mg b.i.d. in the treatment of acute infectious diarrhoea in travellers that Was conducted in 2 centres in India. The primary efficacy end points were Time to last unformed stool (TLUS). TLUS is defined as the interval in hours between the first dose of study drug and the last unformed stool passed, after which clinical cure was declared.
Subjects who meet the criteria for clinical cure immediately after the start of the study and prior to passing any unformed stools are defined as having a TLUS of 0 hours. Patients who terminated the study early due to treatment failure will have a censored TLUS of 120 hours.
The secondary efficacy end points were Clinical cure, Treatment failure, Microbiological cure, Minimum Inhibitory Concentration, Requirement of rescue therapy, Number of unformed stools, Presence, improvement and severity of gastrointestinal symptoms.
The study has been successfully completed in India with the total recruitment of 805 randomized subjects. All the site have been closed as per protocol requirements.