Efficacy of Diosmectite (Smecta®) in the Symptomatic Treatment of Acute Diarrhoea in Adults (ADIASE)

Efficacy of Diosmectite (Smecta®) in the Symptomatic Treatment of Acute Diarrhoea in Adults. A Multicentre, Randomized, Double Blind Placebo Controlled, Parallel, Groups Study

The purpose of the study is to demonstrate that diosmectite efficacy is superior to placebo regarding time to recovery of an acute diarrhoea episode presumed of infectious origin in adult subjects.

Study Overview

• Status: Completed
• Conditions: Acute Diarrhoea
• Intervention / Treatment: Drug: Smecta; Drug: Smecta placebo

• Study Type: Interventional
• Enrollment (Actual): 858
• Phase: Phase 4

Contacts and Locations

Study Locations

• Algeria
  • Algiers, Algeria, 16000
    • Cabinet privé, Coopératives El MOSTAKBAL, BIRKHADEM
  • Algiers, Algeria, 16000
    • CHU Beni Messous
  • Algiers, Algeria, 16000
    • CHU Mustapha
  • Algiers, Algeria, 16000
    • Polyclinique d'el Achour
  • Algiers, Algeria, 16000
    • Polyclinique de Baba Hassen
  • Blida, Algeria, 09000
    • Cabinet privé, 29 avenue amara Youcef
  • Blida, Algeria, 09000
    • EPH Blida
  • Blida, Algeria, 09000
    • EPH EL Afroun
  • Bologhine, Algeria, 16000
    • EPH Bologhine
  • Boumerdas, Algeria, 35000
    • Cabinet privé, cité des 408 lgmts Bt3
  • Constantine, Algeria, 25000
    • CHU BEN BADIS Constantine
  • Deli Ibrahim, Algeria, 16000
    • Polyclinique de Dély Brahim
  • Draria, Algeria, 16000
    • Polyclinique DRARIA
  • Oran, Algeria, 31000
    • CHU Oran
• Czechia
  • Hrochův Týnec, Czechia, 53862
    • OPL, spol. s r.o.
  • Kladno, Czechia, 27201
    • Ordinace PL pro dospělé
  • Kralupy nad Vltavou, Czechia, 278 01
    • Ordinace PL pro dospělé, Poliklinika přízemí, Nerudova
  • Orlová, Czechia, 73514
    • AK Medipraktik, s.r.o
  • Pardubice, Czechia, 53009
    • MUDr. Alena Břeňová - PL pro dospělé
  • Praha, Czechia, 12000
    • Ordinace Bělehradská s.r.o
  • Praha 6, Czechia, 164 00
    • Ordinace PL pro dospělé
  • Praha 6, 2.patro, Czechia, 160 00
    • Ordinace PL pro dospělé
  • Praha 8, Czechia, 182 00
    • Ordinace PL pro dospělé
  • Radotín, Czechia, 15300
    • Praktický lékař Radotín, s.r.o.
  • Vrchlabi, Czechia, 54301
    • Ordinace PL pro dospělé
  • Čáslav, Czechia, 286 01
    • Ordinace PL pro dospělé
  • Karlín
    • Praha 8, Karlín, Czechia, 186 00
      • Ordinace PL pro dospělé
  • Nusle
    • Praha 4, Nusle, Czechia, 140 000
      • Ordinace PL pro dospělé
  • Vysočany
    • Praha 9, Vysočany, Czechia, 190 00
      • Ordinace PL pro dospělé
• Egypt
  • Alexandria, Egypt
    • Clinical Research Center
  • Cairo, Egypt
    • Ain Shams University Hospitals
  • Cairo, Egypt
    • Cairo University
  • Cairo, Egypt
    • Air Force Specialized Hospital
  • Cairo, Egypt
    • Al Hussein University Hospital
  • Cairo, Egypt
    • Badr University Hospital
  • Tanta, Egypt
    • Tanta University
• Lebanon
  • Sidon, Lebanon
    • Hammoud Hospital University Medical Center
• Poland
  • Białystok, Poland, 15-687
    • Komisji Edukacji Narodowej 3B lok. 1
  • Białystok, Poland, 15270
    • CERMED
  • Bychawa, Poland, 23100
    • KLIMED
  • Katowice, Poland, 40-018
    • Indywidualna Specjalistyczna Praktyka Lekarska Roman Spyra
  • Katowice, Poland, 40-709
    • MEKMED S.C. Przychodnia Lekarska NZOZ
  • Kozienice, Poland, 26900
    • Lekarska Spółka Partnerska Familia T S A Gugała
  • Kraków, Poland, 30-664
    • Praktyka Lekarzy Rodzinnych NZOZ
  • Kraków, Poland, 31455
    • Niepubliczny Zakład Opieki Zdrowotnej Ugorek sp. z o.o.
  • Kraków, Poland, 31567
    • Niepubliczny Zakład Opieki Zdrowotnej Centrum Zdrowia i Profilaktyki "Dąbie" spółka z o.o.
  • Lublin, Poland, 20-044
    • Niepubliczny Zakład Opieki Zdrowotnej Praktyka Lekarza Rodzinnego "Eskulap" spółka z o.o.
  • Malbork, Poland, 82-200
    • NZOZ Primed
  • Poznań, Poland, 60529
    • Solumed Research Site
  • Warsaw, Poland, 01868
    • Centrum Medyczne Pratia S.A
  • Warszawa, Poland, 04-041
    • PrzychodniaLekarska ORLIK Sp. z o.o
  • Łomża, Poland, 18404
    • KLIMED
• Tunisia
  • Ben Arous, Tunisia, 41200
    • CSB Zouhour
  • Ben Arous, Tunisia
    • Hopital régional de Ben Arous
  • La Marsa, Tunisia, 2078
    • Centre intermédiaire de Santé de Base
  • La Marsa, Tunisia, 2078
    • Hôpital des Forces de Sécurité Intérieure
  • Sousse, Tunisia, 4000
    • CSB Hedi Chaker
  • Sousse, Tunisia, 4011
    • Hôpital Universitaire Salhoul
  • Sousse, Tunisia, 4022
    • CSB Akouda
  • Sousse, Tunisia, 4022
    • CSB Sidi Bou Ali
  • Sousse, Tunisia, 4031
    • CSB Zouhour
  • Sousse, Tunisia, 4041
    • CSB Nager
  • Sousse, Tunisia, 4041
    • CSB Riadh
  • Sousse, Tunisia, 4051
    • CSB Oued Blibène
  • Sousse, Tunisia, 4060
    • CSB Kalaa Kébira
  • Sousse, Tunisia, 4081
    • CSB Zaouia
  • Tunis, Tunisia, 1006
    • Centre de santé de base Bab Laasal
  • Tunis, Tunisia, 1008
    • Hopital Militaire Principal d'instructions de Tunis
  • Tunis, Tunisia, 2000
    • Centre de santé de base Ras Tabia
  • Tunis, Tunisia, 2009
    • Centre de santé de base Ksar Said
  • Tunis, Tunisia, 2062
    • Centre de santé de base Ibn Khaldoun

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Provision of written informed consent prior to any study related procedures
• Male or female subject (outpatient) legally considered as an adult (age of majority). In Czech Republic, the upper limit of age will be 70 years inclusive. In Egypt, the upper limit of age will be 60 years inclusive.
• Subject has a diagnosis of acute diarrhoea presumed of infectious origin, defined as the passage of 3 or more unformed loose or watery stools (rated according to the Bristol scale) per day within the last 48 hours without associated alarm symptoms
• Subject has, usually, normal bowel habits (Rome III criteria), i.e. at least 3 stools per week and no more than 3 stools per day
• Subject must be willing and able to comply with study restrictions and willing to return to the clinic for the follow up evaluation(s) as specified in the protocol.

Exclusion criteria related to the acute diarrhoea episode:

• At least one of the following alarm symptoms

  • Bloody diarrhoea*,
  • pus in the stools*,
  • fever ≥38°C*,
  • moderate or severe dehydration according to World Health Organisation (WHO) definition, requiring intravenous (IV) rehydration*,
  • repeated vomiting*,
  • persistent abdominal pain* *These symptoms are considered as alarm symptoms
• other episode of acute watery diarrhoea within the previous 30 days,
• persistent diarrhoea, defined as acutely starting episode of diarrhoea lasting more than 14 days,
• history of chronic diarrhoea (Rome III criteria); i.e. 3 or more loose or watery stools per day for at least 12 weeks, consecutive or not, in the preceding 12 months,
• traveller's diarrhoea defined as a diarrhoeal episode due to contamination experienced by subjects having travelled in at risk countries, or coming from abroad and experiencing locally an acute diarrhoea episode, occurring usually within the first 2 weeks of the stay in a foreign environment.

Exclusion criteria related to drugs:

• Diarrhoea suspected to be induced by drug for example:

  • antibiotic therapy, including Clostridium difficile-induced diarrhoea, within 1 week before entry in the study,
  • laxative agent
  • thyroid hormone (at a nonstabilised dosing),
  • intake of other prohibited drugs (as specified in the protocol)
• anti-diarrhoeal agent intake during the last month,
• any subject requiring repeated intake of a drug with a narrow therapeutic margin (as specified in the protocol),
• history of hypersensitivity to diosmectite or its excipients or placebo components,
• subject likely to require treatment during the study with drugs that are not permitted by the study protocol (for example, antibiotic agent, anti-diarrhoeal agent, antiemetic drug, antispasmodic drug),
• use of any investigational medication within the last 30 days before entering this study,
• subject who previously entered in a clinical study within the past 30 days.

Other digestive exclusion criteria:

• History of gastric or intestinal resection, vagotomy,
• known digestive malabsorption disease, including coeliac disease
• known lactose intolerance,
• any suspicion of abdominal surgery need,
• known inflammatory bowel disease.

Other exclusion criteria:

• Known Human immunodeficiency virus (HIV) positive status,
• known or suspected immunosuppression,
• known severe renal insufficiency (including e-GFR not less than 45 mL/min) or hepatic insufficiency,
• known endocrine disease or Type II Diabetes Mellitus with HBA1c more than 8,5% or insulin-dependent diabetes,
• history of, or known current, problems with alcohol abuse and/or known drug addiction (cocaine, heroin, hashish…),
• previous enrolment in this study,
• any mental condition rendering the subject unable to understand the nature, scope and possible consequences of the study, and/or evidence of an uncooperative attitude.
• Pregnant or lactating women

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Smecta; 2 sachets, three times a day (TID), during 5 to 9 days	Drug: Smecta; Other Names: Diosmectite Beaufour
Placebo Comparator: Smecta placebo; 2 sachets of placebo, TID, during 5 to 9 days	Drug: Smecta placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Recovery	Time to recovery was defined as the time from the first study treatment intake recorded in the electronic case report form (eCRF) to the first formed stool followed by a non-watery stool, recorded in the DEB. Results are presented as median time to recovery, calculated using the Kaplan-Meier technique. Participants prematurely withdrawn without recovery or ending the study without recovery were censored (not responders) at the date/time of their last stool as recorded in the DEB. Participants who had not filled in the DEB (i.e. no post-baseline evaluation of stools) were censored at the date/time of their first study treatment intake (or the randomisation date/time if not administered).	From randomisation (Day 1) up to Day 9

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time From Diarrhoea Onset to Recovery	The event of diarrhoea onset (i.e. loose or watery stool) was recorded in the eCRF and the event of recovery (i.e. first formed stool followed by a non-watery stool) was recorded in the DEB. Results are presented as median time from diarrhoea onset to recovery, calculated using the Kaplan-Meier technique. Participants prematurely withdrawn without recovery or ending the study without recovery were censored (not responders) at the date/time of their last stool as recorded in the DEB. Participants who had not filled in the DEB (i.e. no post-baseline evaluation of stools) were censored at the date/time of their first study treatment intake (or the randomisation date/time if not administered).	From randomisation (Day 1) up to Day 9
Time From Diarrhoea Onset to First Formed Stool	The event of diarrhoea onset (i.e. loose or watery stool) was recorded in the eCRF and the event of first formed stool was recorded in the DEB. Results are presented as median time from diarrhoea onset to first formed stool, calculated using the Kaplan-Meier technique. Participants prematurely withdrawn with no formed stool or ending the study with no formed stool were censored at the date/time of their last stool as recorded in the DEB. Participants who had not filled in the DEB (i.e. no post-baseline evaluation of stools) were censored at the date/time of their first study treatment intake (or the randomisation date/time if not administered).	From randomisation (Day 1) up to Day 9
Time From the First Study Treatment Intake to the Last Watery Stool	The event of first study treatment intake was recorded in the eCRF and the event of last watery stool was recorded in the DEB. Results are presented as median time from first study treatment intake to last watery stool, calculated using the Kaplan-Meier technique. Participants prematurely withdrawn with no watery stool or ending the study with no watery stool were censored at the date/time of their last stool as recorded in the DEB. Participants who had not filled in the DEB (i.e. no post-baseline evaluation of stools) were censored at the date/time of their first study treatment intake (or the randomisation date/time if not administered).	From randomisation (Day 1) up to Day 9
Number of Stools, Per 12-Hour Period	Number of stools, per 12-hour period, was recorded in the DEB.	From randomisation (Day 1) up to Day 9
Number of Watery Stools, Per 12-Hour Period	Number of watery stools, per 12-hour period, was recorded in the DEB.	From randomisation (Day 1) up to Day 9
Percentage of Participants With Associated Symptoms, Per 12-Hour Period	Percentage of participants with associated symptoms (at least 1 symptom of nausea, vomiting, abdominal pain or anal irritation) per 12-hour period is presented. Nausea, vomiting, abdominal pain and anal irritation were recorded in the DEB.	From randomisation (Day 1) up to Day 9
Abdominal Pain Intensity Scores, Per 12-Hour Period	Abdominal pain intensity per 12-hour period was recorded in the DEB. Abdominal pain intensity was rated with a 5-point ordinal scale: 0 = absent, 1= mild, 2 =moderate, 3 = severe, 4= very severe. Higher scores indicate a worse outcome. The median abdominal pain intensity score for each 12-hour period is presented.	From randomisation (Day 1) up to Day 9

Collaborators and Investigators

• Sponsor: Ipsen

Study record dates

Study Major Dates

• Study Start (Actual): March 17, 2016
• Primary Completion (Actual): April 8, 2019
• Study Completion (Actual): April 8, 2019

Study Registration Dates

• First Submitted: March 4, 2016
• First Submitted That Met QC Criteria: March 8, 2016
• First Posted (Estimate): March 9, 2016

Study Record Updates

• Last Update Posted (Actual): November 5, 2020
• Last Update Submitted That Met QC Criteria: November 4, 2020
• Last Verified: November 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Signs and Symptoms, Digestive; Diarrhea
• Other Study ID Numbers: F-FR-00250-105; 2015-001138-10 (EudraCT Number)