Changes to trial information |
Section Name
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Field Name
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Date
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Reason
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Old Value
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Updated Value
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Trial Information |
Trial description |
15/07/2025 |
Ghana is excluded from the clinical trial |
Buruli ulcer (BU), caused by Mycobacterium ulcerans (Mul), affects skin, soft tissues and bones causing long-term morbidity, stigma and disability. The greatest burden falls on children in sub-Saharan Africa. Treating BU requires 8-weeks with daily rifampicin and clarithromycin, wound care, and sometimes tissue grafting and surgery. Wound healing can take up to one year. Compliance to treatment is challenging due to socioeconomic determinants and may pose an unbearable financial burden to the household.
Recent studies led by members of this Consortium demonstrated that beta-lactams combined with rifampicin and clarithromycin are synergistic against Mul. Amoxicillin/clavulanate is oral, suitable for treatment in adults and children, and readily available with an established clinical safety profile.
We propose a multi-country, randomized, controlled, open label, non-inferiority Phase III clinical trial in Ghana, Côte d’Ivoire and Togo with participants stratified according to BU category lesions and randomized in two oral regimens:
(i) Standard [RC8]: rifampicin plus clarithromycin (RC) therapy for 8 weeks; and
(ii) Investigational [RCA4]: standard (RC) plus amoxicillin/clavulanate (A) for 4 weeks.
The primary efficacy outcome will be cure rate, i.e., lesion healing without recurrence and without excision surgery 12 months after start of treatment.
If successful, this study will create a new paradigm for BU treatment, which could inform changes in WHO policy and practice. This trial may also provide information on treatment shortening strategies for other mycobacterial infections, such as tuberculosis or leprosy, for which rifampicin is the cornerstone drug in therapy. |
Buruli ulcer (BU), caused by Mycobacterium ulcerans (Mul), affects skin, soft tissues and bones causing long-term morbidity, stigma and disability. The greatest burden falls on children in sub-Saharan Africa. Treating BU requires 8-weeks with daily rifampicin and clarithromycin, wound care, and sometimes tissue grafting and surgery. Wound healing can take up to one year. Compliance to treatment is challenging due to socioeconomic determinants and may pose an unbearable financial burden to the household.
Recent studies led by members of this Consortium demonstrated that beta-lactams combined with rifampicin and clarithromycin are synergistic against Mul. Amoxicillin/clavulanate is oral, suitable for treatment in adults and children, and readily available with an established clinical safety profile.
We propose a multi-country, randomized, controlled, open label, non-inferiority Phase III clinical trial in Côte d’Ivoire and Togo with participants stratified according to BU category lesions and randomized in two oral regimens:
(i) Standard [RC8]: rifampicin plus clarithromycin (RC) therapy for 8 weeks; and
(ii) Investigational [RCA4]: standard (RC) plus amoxicillin/clavulanate (A) for 4 weeks.
The primary efficacy outcome will be cure rate, i.e., lesion healing without recurrence and without excision surgery 12 months after start of treatment.
If successful, this study will create a new paradigm for BU treatment, which could inform changes in WHO policy and practice. This trial may also provide information on treatment shortening strategies for other mycobacterial infections, such as tuberculosis or leprosy, for which rifampicin is the cornerstone drug in therapy. |
Section Name
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Field Name
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Date
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Reason
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Old Value
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Updated Value
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Trial Information |
Actual trial start date |
12/05/2025 |
Recruitment start was delayed |
|
01 Mar 2023 |
Section Name
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Field Name
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Date
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Reason
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Old Value
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Updated Value
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Trial Information |
Anticipated date of last follow up |
12/05/2025 |
The recruitment has been extended, and thereby, the last follow up will be 31 May 2027 |
30 Nov 2025 |
31 May 2027 |
Section Name
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Field Name
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Date
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Reason
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Old Value
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Updated Value
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Trial Information |
Final no of participants |
16/09/2022 |
There are two populations.
174 is the number of participants, which include 134 who are PCR confirmed and 40 non PCR-confirmed. This is why the numbers are different.
The relevant number is the PCR-confirmed. However, due to the possible lost of follow-up and PCR-confirmation rate, I will state 174 as the total and 87 under each intervention arm. |
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174 |
Section Name
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Field Name
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Date
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Reason
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Old Value
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Updated Value
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Trial Information |
Recruitment status |
03/10/2023 |
Clinical sites in côte d'Ivoire an Togo started recruitment |
Not yet recruiting |
Recruiting |
Section Name
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Field Name
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Date
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Reason
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Old Value
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Updated Value
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Eligibility |
Age group |
09/06/2025 |
The minimum age is 5 years |
Child: 6 Year-12 Year, Adolescent: 13 Year-18 Year, Adult: 19 Year-44 Year, Middle Aged: 45 Year(s)-64 Year(s), Aged: 65+ Year(s) |
Preschool Child: 2 Year-5 Year, Child: 6 Year-12 Year, Adolescent: 13 Year-18 Year, Adult: 19 Year-44 Year, Middle Aged: 45 Year(s)-64 Year(s), Aged: 65+ Year(s) |
Section Name
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Field Name
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Date
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Reason
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Old Value
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Updated Value
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Intervention |
Intervention List |
16/09/2022 |
There are two different populations taking into account the possible lost of follow-up and PCR-confirmation rate.
174 is the number of participants, which include 134 who are PCR confirmed and 40 non PCR-confirmed.
The relevant number is the PCR-confirmed. However, due to the possible lost of follow-up and PCR-confirmation rate, I will state 174 as the total and 87 under each intervention arm, although only 67 PCR-confirmed participants are required under each intervention arm. |
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Control Group, Standard RC8, Treatment will be rifampicin (600 mg, daily) and clarithromycin (500 mg, twice daily) for 8 weeks. On the posology, dosage for rifampicin and clarithromycin will be standardized according to patient body weight following WHO guidelines. In general, for a 60 kg adult dosage will be RIF, 10 mg/kg and CLA, 7.5 mg/kg., 8 weeks, Rifampicin plus clarithromycin (RC) therapy for 8 weeks, 87, Active-Treatment of Control Group |
Section Name
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Field Name
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Date
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Reason
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Old Value
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Updated Value
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Intervention |
Intervention List |
16/09/2022 |
There are two different populations taking into account the possible lost of follow-up and PCR-confirmation rate.
174 is the number of participants, which include 134 who are PCR confirmed and 40 non PCR-confirmed.
The relevant number is the PCR-confirmed. However, due to the possible lost of follow-up and PCR-confirmation rate, I will state 174 as the total and 87 under each intervention arm, although only 67 PCR-confirmed participants are required under each intervention arm. |
|
Experimental Group, Investigational RCA4, Treatment will be rifampicin (600 mg, daily) and clarithromycin (500 mg, twice daily) for 8 weeks. On the posology, dosage for rifampicin and clarithromycin will be standardized according to patient body weight following WHO guidelines. In general, for a 60 kg adult dosage will be RIF, 10 mg/kg and CLA, 7.5 mg/kg.
Dosages for amoxicillin/clavulanate are calculated according to manufacturer indications:
Dose of amoxicillin/clavulanate 1000/125 mg twice daily, which makes a total of 2000/250 mg/day, for patients over 40 kg, and 22.5/5.6 mg/kg twice daily, which makes a total of 45/11.25 mg/kg/day, for those equal and below 40 kg. For children, posology will be adapted to the age of the patient according to drug manufacturer indications. Frequency of AMX/CLV administration will match that of CLA, twice daily., 4 weeks, Standard (Rifampicin and clarithromycin) plus amoxicillin/clavulanate (A) for 4 weeks. , 87, |
Section Name
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Field Name
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Date
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Reason
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Old Value
|
Updated Value
|
Intervention |
Intervention List |
16/09/2022 |
There are two different populations taking into account the possible lost of follow-up and PCR-confirmation rate.
174 is the number of participants, which include 134 who are PCR confirmed and 40 non PCR-confirmed.
The relevant number is the PCR-confirmed. However, due to the possible lost of follow-up and PCR-confirmation rate, I will state 174 as the total and 87 under each intervention arm. |
Control Group, Standard RC8, Treatment will be rifampicin (600 mg, daily) and clarithromycin (500 mg, twice daily) for 8 weeks. On the posology, dosage for rifampicin and clarithromycin will be standardized according to patient body weight following WHO guidelines. In general, for a 60 kg adult dosage will be RIF, 10 mg/kg and CLA, 7.5 mg/kg., 8 weeks, Rifampicin plus clarithromycin (RC) therapy for 8 weeks, 67, Active-Treatment of Control Group |
Control Group, Standard RC8, Treatment will be rifampicin (600 mg, daily) and clarithromycin (500 mg, twice daily) for 8 weeks. On the posology, dosage for rifampicin and clarithromycin will be standardized according to patient body weight following WHO guidelines. In general, for a 60 kg adult dosage will be RIF, 10 mg/kg and CLA, 7.5 mg/kg., 8 weeks, Rifampicin plus clarithromycin (RC) therapy for 8 weeks, 87, Active-Treatment of Control Group |
Section Name
|
Field Name
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Date
|
Reason
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Old Value
|
Updated Value
|
Intervention |
Intervention List |
16/09/2022 |
There are two different populations taking into account the possible lost of follow-up and PCR-confirmation rate.
174 is the number of participants, which include 134 who are PCR confirmed and 40 non PCR-confirmed.
The relevant number is the PCR-confirmed. However, due to the possible lost of follow-up and PCR-confirmation rate, I will state 174 as the total and 87 under each intervention arm although only 67 PCR-confirmed participants are required under each intervention arm. |
Experimental Group, Investigational RCA4, Treatment will be rifampicin (600 mg, daily) and clarithromycin (500 mg, twice daily) for 8 weeks. On the posology, dosage for rifampicin and clarithromycin will be standardized according to patient body weight following WHO guidelines. In general, for a 60 kg adult dosage will be RIF, 10 mg/kg and CLA, 7.5 mg/kg.
Dosages for amoxicillin/clavulanate are calculated according to manufacturer indications:
Dose of amoxicillin/clavulanate 1000/125 mg twice daily, which makes a total of 2000/250 mg/day, for patients over 40 kg, and 22.5/5.6 mg/kg twice daily, which makes a total of 45/11.25 mg/kg/day, for those equal and below 40 kg. For children, posology will be adapted to the age of the patient according to drug manufacturer indications. Frequency of AMX/CLV administration will match that of CLA, twice daily., 4 weeks, Standard (Rifampicin and clarithromycin) plus amoxicillin/clavulanate (A) for 4 weeks. , 67, |
Experimental Group, Investigational RCA4, Treatment will be rifampicin (600 mg, daily) and clarithromycin (500 mg, twice daily) for 8 weeks. On the posology, dosage for rifampicin and clarithromycin will be standardized according to patient body weight following WHO guidelines. In general, for a 60 kg adult dosage will be RIF, 10 mg/kg and CLA, 7.5 mg/kg.
Dosages for amoxicillin/clavulanate are calculated according to manufacturer indications:
Dose of amoxicillin/clavulanate 1000/125 mg twice daily, which makes a total of 2000/250 mg/day, for patients over 40 kg, and 22.5/5.6 mg/kg twice daily, which makes a total of 45/11.25 mg/kg/day, for those equal and below 40 kg. For children, posology will be adapted to the age of the patient according to drug manufacturer indications. Frequency of AMX/CLV administration will match that of CLA, twice daily., 4 weeks, Standard (Rifampicin and clarithromycin) plus amoxicillin/clavulanate (A) for 4 weeks. , 87, |
Section Name
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Field Name
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Date
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Reason
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Old Value
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Updated Value
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Recruitment Centre |
RecruitmentCentre List |
09/07/2025 |
Ghana did not start the recruitment and is not a country with clinical sites anymore |
Jacobu Government Hospital , Amansie Central, Jacobu, , Ghana |
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Section Name
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Field Name
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Date
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Reason
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Old Value
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Updated Value
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Recruitment Centre |
RecruitmentCentre List |
09/07/2025 |
Ghana did not start the recruitment and is not a country with clinical sites anymore |
Nkawie Hospital , Nkawie Road, Toase, , Ghana |
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Section Name
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Field Name
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Date
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Reason
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Old Value
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Updated Value
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Recruitment Centre |
RecruitmentCentre List |
09/07/2025 |
Additional clinical site |
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Hopital General Taabo, Taabo, Taabo, , Cote Divoire |
Section Name
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Field Name
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Date
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Reason
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Old Value
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Updated Value
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Recruitment Centre |
RecruitmentCentre List |
09/07/2025 |
Additional clinical site |
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Hopital General Djekanou, Djekanou, Djekanou, , Cote Divoire |
Section Name
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Field Name
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Date
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Reason
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Old Value
|
Updated Value
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Recruitment Centre |
RecruitmentCentre List |
09/07/2025 |
Additional clinical site |
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Hopital Saint Michel Zoukougbeu, Zoukougbeu, Zoukougbeu, , Cote Divoire |
Section Name
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Field Name
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Date
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Reason
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Old Value
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Updated Value
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Ethics |
Ethics List |
03/10/2023 |
Approval was obtained |
FALSE, Comite National dEthique des Sciences de la Vie de Cote dIvoire, CHU de Cocody Institut Pasteur de Cote dIvoire, Abidjan-Cocody , 82V3 MQ3, Cote Divoire, 12 Sep 2022, , 002723453392, cnesvscotedivoire@gmail.com, |
TRUE, Comite National dEthique des Sciences de la Vie de Cote dIvoire, CHU de Cocody Institut Pasteur de Cote dIvoire, Abidjan-Cocody , 82V3 MQ3, Cote Divoire, 12 Sep 2022, 30 Sep 2022, 002723453392, cnesvscotedivoire@gmail.com, |
Section Name
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Field Name
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Date
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Reason
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Old Value
|
Updated Value
|
Ethics |
Ethics List |
19/06/2025 |
Approval was obtained |
TRUE, Comite National dEthique des Sciences de la Vie de Cote dIvoire, CHU de Cocody Institut Pasteur de Cote dIvoire, Abidjan-Cocody , 82V3 MQ3, Cote Divoire, , 30 Sep 2022, 002723453392, cnesvscotedivoire@gmail.com, |
TRUE, Comite National dEthique des Sciences de la Vie de Cote dIvoire, CHU de Cocody Institut Pasteur de Cote dIvoire, Abidjan-Cocody , 82V3 MQ3, Cote Divoire, , 30 Sep 2022, 002723453392, cnesvscotedivoire@gmail.com, 23991_18631_4737.pdf |
Section Name
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Field Name
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Date
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Reason
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Old Value
|
Updated Value
|
Ethics |
Ethics List |
19/06/2025 |
Ghana is not longer recruiting in the clinical trial. Therefore, no final approval was needed. |
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|
Section Name
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Field Name
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Date
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Reason
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Old Value
|
Updated Value
|
Ethics |
Ethics List |
03/10/2023 |
Approval was obtained |
FALSE, Comite de Bioethique pour la Recherche en Sante CBRS, Ministere de la Sante, Direction des Pharmacies, Angle avenue Sarakawa et avenue du 2 Fevrier, Lome, BP 386, Togo, 18 Aug 2022, , +2282213801, info@cbrstogo.org, |
TRUE, Comite de Bioethique pour la Recherche en Sante CBRS, Ministere de la Sante, Direction des Pharmacies, Angle avenue Sarakawa et avenue du 2 Fevrier, Lome, BP 386, Togo, 18 Aug 2022, 12 Oct 2022, +2282213801, info@cbrstogo.org, |
Section Name
|
Field Name
|
Date
|
Reason
|
Old Value
|
Updated Value
|
Ethics |
Ethics List |
19/06/2025 |
Approval was obtained |
TRUE, Comite de Bioethique pour la Recherche en Sante CBRS, Ministere de la Sante, Direction des Pharmacies, Angle avenue Sarakawa et avenue du 2 Fevrier, Lome, BP 386, Togo, , 12 Oct 2022, +2282213801, info@cbrstogo.org, |
TRUE, Comite de Bioethique pour la Recherche en Sante CBRS, Ministere de la Sante, Direction des Pharmacies, Angle avenue Sarakawa et avenue du 2 Fevrier, Lome, BP 386, Togo, , 12 Oct 2022, +2282213801, info@cbrstogo.org, 23991_18652_4737.pdf |
Section Name
|
Field Name
|
Date
|
Reason
|
Old Value
|
Updated Value
|
Contact People |
Contacs List |
09/06/2025 |
This is a collaborator. Contact, only the PI. |
Principal Investigator, Richard, Odame Phillips, Dr., phillips@kccr.de, , +233322060511, Kumasi Centre for Collaborative Research in Tropical medicine KCCR, Kwame Nkrumah University of Science and Technology KNUST, South-end, Asuogya Rd , Kumasi, , Ghana, Scientific Director |
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Section Name
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Field Name
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Date
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Reason
|
Old Value
|
Updated Value
|
Contact People |
Contacs List |
09/06/2025 |
This is a collaborator. Contact, only the PI. |
Principal Investigator, Denis , Agbenyigan Yawovi Gadah, Mr., denis.gadah@dahw.org, , +22822232230, DAHW Deutsche Lepra und Tuberkulosehilfe e V , Avenue De la Providence, Centre Dermatologique Gbossime, Lome, , Togo, Program Director DAH |
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Section Name
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Field Name
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Date
|
Reason
|
Old Value
|
Updated Value
|
Contact People |
Contacs List |
09/06/2025 |
This is a collaborator. Contact, only the PI. |
Principal Investigator, Mamadou, Kaloga, Prof., kaloganas@yahoo.fr, , +22507845645, C.H.U de Treichville, 14 B.P. 1960 Abidjan 14, Abidjan, , Cote Divoire, Professeur Titulaire |
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Section Name
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Field Name
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Date
|
Reason
|
Old Value
|
Updated Value
|
Contact People |
Contacs List |
09/06/2025 |
This is a collaborator. Contact, only the PI. |
Principal Investigator, Israel, Cruz Mata, Dr., cruzi@isciii.es, , +34918222312, National School of Public Health, Instituto de Salud Carlos III, Sinesio Delgado 8, Madrid, , Spain, Head International H |
|