ERASE: Rifamycin SV-MMX® Tablets Versus Ciprofloxacin Capsules in Acute Traveller's Diarrhoea

• Sponsor: Dr. Falk Pharma GmbH (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01208922
• Collaborator: (none)
• Enrollment: 835
• Locations: 19
• Arms: 2
• Duration (Months): 66
• Patients Per Site: 43.9
• Patients Per Site Per Month: 0.7

Study Details

Study Description

Brief Summary

The purpose of this study is to prove the non-inferiority of Rifamycin SV-MMX® versus Ciprofloxacin for the treatment of adults with traveller's diarrhoea.

Condition or Disease	Intervention/Treatment	Phase
Traveler's Diarrhea	Drug: Rifamycin SV-MMX®; Drug: Ciprofloxacin	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 835 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: 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
• Study Start Date: Nov 1, 2010
• Actual Primary Completion Date: Jan 1, 2016
• Actual Study Completion Date: May 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Group A Rifamycin SV-MMX® 200 mg tablets	Drug: Rifamycin SV-MMX®; 2 Rifamycin SV-MMX® 200 mg tablets and 1 placebo to ciprofloxacin capsule, b.i.d.
Active Comparator: Group B Ciprofloxacin 500 mg capsules	Drug: Ciprofloxacin; 1 ciprofloxacin 500 mg capsule and 2 placebos to Rifamycin SV-MMX® 200 mg tablets, b.i.d.

Outcome Measures

Primary Outcome Measures

1. Time to Last Unformed Stool (TLUS) [5 days]

   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.

Secondary Outcome Measures

1. Number of Patients With Clinical Cure [5 days]

   Clinical Cure Rate: 24-hour period with no clinical symptoms except mild flatulence, no fever, no watery stools and no more than 2 soft stools OR 48-hour period with no stools or only formed stools, and no fever, with our without symptoms of enteric infection.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 85 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Signed informed consent,

• Men or women between 18 and 85 years of age,

• History of arriving from their country of residence in the industrialized part of the world within the past 4 weeks,

• 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),

• Presence of one or more signs or symptoms of enteric infection (moderate to severe gas/flatulence, nausea, vomiting, abdominal cramps or pain, rectal tenesmus, fecal urgency),

• Women of childbearing potential had to apply during the entire duration of the study a highly effective method of birth control

Exclusion Criteria:

• Residency in any country with high incidence rate of TD within the past 6 months,

• Fever (defined as a body (oral) temperature >100.4°F or 38.0°C; antipyretic medication should not have been administered in the 6 hours prior to this assessment),

• Known or suspected infection with non-bacterial pathogen,

• Presence of diarrhoea of >72 hours duration,

• Presence of grossly bloody stool,

• Presence of moderate or severe dehydration (i.e. symptoms of hypovolemia such as orthostatic hypotension, dizziness or wrinkling of skin),

• History of inflammatory bowel disease or celiac disease,

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Site 401	Quito		Ecuador
2	Site 200	Quetzaltenango		Guatemala
3	Site 101	Mapusa	Karaswada	India
4	Site 124	Ajmer		India
5	Site 118	Bardez		India
6	Site 120	Calangute		India
7	Site 104	Hyderabad		India
8	Site 114	Kolkata		India
9	Site 116	Lucknow		India
10	Site 107	Margao		India
11	Site 110	Margao		India
12	Site 123	New Delhi		India
13	Site 122	Panaji		India
14	Site 102	Pondichéry		India
15	Site 115	Pushkar		India
16	Site 119	Salcette		India
17	Site 111	Tiswadi		India
18	Site 109	Varanasi		India
19	Site 103	Vijayawada		India

Sponsors and Collaborators

• Dr. Falk Pharma GmbH

Investigators

• Principal Investigator: Professor Robert Steffen, M. D., University of Zurich, Switzerland

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Dr. Falk Pharma GmbH
• ClinicalTrials.gov Identifier: NCT01208922
• Other Study ID Numbers: RIT-1/AID
• First Posted: Sep 24, 2010
• Last Update Posted: Feb 27, 2019
• Last Verified: Oct 1, 2018

• Additional relevant MeSH terms: Dysentery; Diarrhea; Ciprofloxacin; Rifamycins; Rifamycin SV

Study Results

Participant Flow

Recruitment Details	Recruited from November 2010 until January 2016
Pre-assignment Detail	A total of 835 patients were enrolled and were randomised to one of the 2 treatment groups according to the randomisation plan. All randomised patients received at least one dose of study medication.

Arm/Group Title	Rifamycin Group	Ciprofloxacin Group
Arm/Group Description	Rifamycin SV-MMX® 200 mg tablets Rifamycin SV-MMX®: 2 Rifamycin SV-MMX® 200 mg tablets and 1 placebo to ciprofloxacin capsule, b.i.d.	Ciprofloxacin 500 mg capsules Ciprofloxacin: 1 ciprofloxacin 500 mg capsule and 2 placebos to Rifamycin SV-MMX® 200 mg tablets, b.i.d.
Period Title: Overall Study
STARTED	420	415
COMPLETED	409	405
NOT COMPLETED	11	10

Baseline Characteristics

Arm/Group Title	Group A	Group B	Total
Arm/Group Description	Rifamycin SV-MMX® 200 mg tablets Rifamycin SV-MMX®: 2 Rifamycin SV-MMX® 200 mg tablets and 1 placebo to ciprofloxacin capsule, b.i.d.	Ciprofloxacin 500 mg capsules Ciprofloxacin: 1 ciprofloxacin 500 mg capsule and 2 placebos to Rifamycin SV-MMX® 200 mg tablets, b.i.d.	Total of all reporting groups
Overall Participants	420	415	835
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	40.0 (16.1)	40.4 (16.6)	40.2 (16.3)
Sex: Female, Male (Count of Participants)
Female	215 51.2%	197 47.5%	412 49.3%
Male	205 48.8%	218 52.5%	423 50.7%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	75 17.9%	68 16.4%	143 17.1%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	1 0.2%	1 0.1%
White	342 81.4%	344 82.9%	686 82.2%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	3 0.7%	2 0.5%	5 0.6%
Region of Enrollment (participants) [Number]
Ecuador	1 0.2%	0 0%	1 0.1%
Guatemala	14 3.3%	15 3.6%	29 3.5%
India	405 96.4%	400 96.4%	805 96.4%

Outcome Measures

1. Primary Outcome

Title	Time to Last Unformed Stool (TLUS)
Description	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.
Time Frame	5 days

Outcome Measure Data

Analysis Population Description

Efficacy results were reported for Full Analysis Set, which all randomised patients (as randomised) who received at least one dose of study medication. Patients with uncertainty as to whether they had received study medication or not (e.g., due to lost to follow-up) were included.

Arm/Group Title	Group A	Group B
Arm/Group Description	Rifamycin SV-MMX® 200 mg tablets Rifamycin SV-MMX®: 2 Rifamycin SV-MMX® 200 mg tablets and 1 placebo to ciprofloxacin capsule, b.i.d.	Ciprofloxacin 500 mg capsules Ciprofloxacin: 1 ciprofloxacin 500 mg capsule and 2 placebos to Rifamycin SV-MMX® 200 mg tablets, b.i.d.
Measure Participants	420	415
Median (95% Confidence Interval) [hours]	44.3	40.3

2. Secondary Outcome

Title	Number of Patients With Clinical Cure
Description	Clinical Cure Rate: 24-hour period with no clinical symptoms except mild flatulence, no fever, no watery stools and no more than 2 soft stools OR 48-hour period with no stools or only formed stools, and no fever, with our without symptoms of enteric infection.
Time Frame	5 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Group A	Group B
Arm/Group Description	Rifamycin SV-MMX® 200 mg tablets Rifamycin SV-MMX®: 2 Rifamycin SV-MMX® 200 mg tablets and 1 placebo to ciprofloxacin capsule, b.i.d.	Ciprofloxacin 500 mg capsules Ciprofloxacin: 1 ciprofloxacin 500 mg capsule and 2 placebos to Rifamycin SV-MMX® 200 mg tablets, b.i.d.
Measure Participants	420	415
Count of Participants [Participants]	357 85%	352 84.8%

Adverse Events

Time Frame	An average of 1 month
Adverse Event Reporting Description	Non-serious AEs were analysed as Treatment-Emergent AEs defined as all AEs with onset after treatment day 1 but not after the last day with study drug administration.
Arm/Group Title	Group A		Group B
Arm/Group Description	Rifamycin SV-MMX® 200 mg tablets Rifamycin SV-MMX®: 2 Rifamycin SV-MMX® 200 mg tablets and 1 placebo to ciprofloxacin capsule, b.i.d.		Ciprofloxacin 500 mg capsules Ciprofloxacin: 1 ciprofloxacin 500 mg capsule and 2 placebos to Rifamycin SV-MMX® 200 mg tablets, b.i.d.
All Cause Mortality
	Group A		Group B
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/420 (0%)		0/415 (0%)
Serious Adverse Events
	Group A		Group B
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/420 (0%)		0/415 (0%)
Other (Not Including Serious) Adverse Events
	Group A		Group B
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	36/420 (8.6%)		32/415 (7.7%)
Gastrointestinal disorders
Diarrhoea	8/420 (1.9%)	8	6/415 (1.4%)	6
Nausea	6/420 (1.4%)	6	6/415 (1.4%)	6
Flatulence	5/420 (1.2%)	5	6/415 (1.4%)	6
Abdominal pain	4/420 (1%)	4	5/415 (1.2%)	5
Nervous system disorders
Headache	13/420 (3.1%)	13	9/415 (2.2%)	9

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.