Mycobacterium Ulcerans DiseaseBurulitimeNCT01432925
Timing of Surgical Intervention in Buruli Ulcer Patients Treated With Antibiotics
A study testing surgical intervention on Buruli ulcer in people with Mycobacterium Ulcerans Disease and Buruli Ulcer, run by University Medical Center Groningen at 2 sites in Benin.
Trial summary
SUMMARY Rationale: Buruli ulcer, caused by Mycobacterium ulcerans, is an ulcerative disease endemic in West Africa. It often leads to functional limitations. Treatment was by extensive surgery, until in 2005 gradually antibiotic treatment for eight weeks with rifampicin and streptomycin was added. Read more about this study
- Who is it for?
- Ages 3 years and older
- Conditions the study is for
- Mycobacterium Ulcerans Disease, Buruli Ulcer
- What is being tested?
- surgical intervention on Buruli ulcer
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 119 participants
- Where
- 2 sitesBenin
- Study dates
- Sep 2011to Dec 2016
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 3 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Patients with a clinical picture of Buruli ulcer disease in the districts covered by the Buruli ulcer centers in Lalo and Allada, Benin, will be included at start of antibiotic treatment.
- All stages of the disease will be included. Only patients with confirmed disease by direct microscopy following acid-fast staining or PCR will be included.
Who cannot join
- Patients not on the standard treatment of eight weeks of rifampicin and streptomycin for any reason, will be excluded from this study.
- Treatment with macrolide or quinolone antibiotics, or antituberculous medication, or immune-modulatory drugs including corticosteroids within the previous one month.
- Patients not compliant with the antibiotic therapy will be excluded as well. Non-compliance is defined as the use of < 70 % of the prescribed antibiotics.
- Patients with a contraindication for general anaesthesia are not able to participate.
- Pregnancy.
- Osteomyelitis.
Show all 12Show fewer
- Lesion close to the eye, with preferred standard treatment to wait for effect antibiotic treatment on extent surgery.
- The BUFLS (Buruli ulcer functional limitation score) cannot be applied to children below three years and therefore will not participate.
- Patients reporting to refuse surgery at any point in the intended treatment, cannot be included.
- Any situation or condition which may compromise ability to comply with the trial procedures.
- Patients known to be HIV positive.
- Lack of willingness to give informed consent (and/or assent by parent/legal representative).
Trial locations and contacts
2 sites in 1 country.
About this study
Official title: Timing of the Decision on Surgical Intervention for Buruli Ulcer Patients Treated With Rifampicin/Streptomycin
SUMMARY
Rationale: Buruli ulcer, caused by Mycobacterium ulcerans, is an ulcerative disease endemic in West Africa. It often leads to functional limitations. Treatment was by extensive surgery, until in 2005 gradually antibiotic treatment for eight weeks with rifampicin and streptomycin was added. Observation of Buruli ulcer lesions of limited size during antibiotic treatment showed that during treatment there is a paradoxical increase of the lesion, with a decrease of the lesion after week 14. Current WHO protocols advise to decide whether surgery is needed four weeks after the start of antibiotics. This might be too early in the healing process. The investigators hypothesize that delay in surgery is safe, and that it results in a reduction of the number of surgical interventions.
Read more
Objectives:
Primary Objective of this study is to compare the need for surgical treatment in standard timing of surgery at the end of eight weeks antimicrobial treatment with a policy to postpone surgical treatment until week 14.
Secondary Objectives are to study whether postponing surgery leads to less extensive surgery and a change in frequency of functional limitations;
Study design:
Patients will be randomized for surgery at week 8 after start of antibiotic treatment and week 14 after start of treatment. Reasons for treating doctors to decide to intervene with surgery will be according to current clinical practice and will be clearly defined in this protocol. Standard care of eight weeks of rifampicin and streptomycin will be given. All patients will be followed and lesional size using acetate sheet recordings will be used during follow-up.
Study population: Patients with a clinical picture of Buruli ulcer disease confirmed by diagnostic tests in the districts covered by the Buruli ulcer centers in Lalo and Allada, Benin. Patients who are pregnant, have a contraindication for general anaesthesia and children below three years old will be excluded. 130 Patients in each treatment arm will be included to detect a difference in percentage of patients needing surgery of 20 percent.
Main study parameters/endpoints: Primary outcome measure is the number of patients healed without surgery. Secondary outcome measures are the extent of surgery by measurement of lesional size, functional limitations after the end of treatment and one year after the start of treatment and the duration of admission.
- Conditions
- Mycobacterium Ulcerans Disease, Buruli Ulcer
- Being tested
- surgical intervention on Buruli ulcer
- Keywords
- Buruli ulcer, Mycobacterium ulcerans, Streptomycin, Rifampicin, Functional limitations, surgery, Bénin
- Medical subject headings
- Buruli Ulcer
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
surgical intervention on Buruli ulcerProcedure or surgery
Can the need for surgical intervention be avoided by delay of the decision on surgical intervention, comparing the need on surgical intervention from time points of week 8 and week 14 (number of weeks after start of antibiotic treatment with streptomycin/rifampicin).
| Study group | Role | What they receive |
|---|---|---|
| evaluation surgical intervention at week 8 | Other | Not described Receives: Procedure: surgical intervention on Buruli ulcer |
| evaluation surgical intervention at week 14 | Other | Not described Receives: Procedure: surgical intervention on Buruli ulcer |
What is being measured
The primary outcome is the main question the study is designed to answer.
Healing without surgical intervention
measurement of lesions at follow up visit, if lesion closed-> healed.
Measured: one year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Sep 2011 (estimated)
- Study startSep 2011
- Primary completionDec 2016
- Study completionDec 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Mycobacterium Ulcerans DiseaseStudies of the same condition, open and under way.
- More trials run by University Medical Center GroningenThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 119 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Medical Center Groningen
- Sponsor type
- University, hospital or other
- Collaborators
- PNLUB, Ministère de la santé, Cotonou, République du Bénin., Laboratoire de Référence des Mycobactéries
- Responsible party
- Principal investigator, Ymkje Stienstra, University Medical Center Groningen
- Investigators
- D Agossadou, MD, Principal investigator, Program national lutte contre la lèpre et l'ulcère de Buruli, ministère de la santé, Hospital LaloG Sopoh, MD PhD, Principal investigator, Program national lutte contre la lèpre et l'ulcère de Buruli, Ministère de la Santé, Cotonou, Bénin, hospital AlladaTjip S van der Werf, MD PhD, Principal investigator, UMCG - internal medicine/infectious diseasesR OC Johnson, MD PhD, Principal investigator, Cotonou, Bénin
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01432925
- Sponsor's protocol ID
- BURULIVENI
- Acronym
- Burulitime
- Status last verified
- Jul 2019
- First submitted
- 8 Sep 2011
- Last updated
- 22 Jul 2019
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Wadagni AC, Barogui YT, Johnson RC, Sopoh GE, Affolabi D, van der Werf TS, de Zeeuw J, Kleinnijenhuis J, Stienstra Y. Delayed versus standard assessment for excision surgery in patients with Buruli ulcer in Benin: a randomised controlled trial. Lancet Infect Dis. 2018 Jun;18(6):650-656. doi: 10.1016/S1473-3099(18)30160-9. Epub 2018 Apr 5.
PubMed 29605498Barogui YT, Klis SA, Johnson RC, Phillips RO, van der Veer E, van Diemen C, van der Werf TS, Stienstra Y. Genetic Susceptibility and Predictors of Paradoxical Reactions in Buruli Ulcer. PLoS Negl Trop Dis. 2016 Apr 20;10(4):e0004594. doi: 10.1371/journal.pntd.0004594. eCollection 2016 Apr.
PubMed 27097163
Study at a glance
From the registry record, last updated by the sponsor on 22 Jul 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Timing of the Decision on Surgical Intervention for Buruli Ulcer Patients Treated With Rifampicin/Streptomycin
- ClinicalTrials.gov ID
- NCT01432925
- Acronym / sponsor ID
- Burulitime / BURULIVENI
- Conditions
- Mycobacterium Ulcerans Disease, Buruli Ulcer
- Keywords
- Buruli ulcer, Mycobacterium ulcerans, Streptomycin, Rifampicin, Functional limitations, surgery, Bénin
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 119 participants (actual)
- Lead sponsor
- University Medical Center GroningenUniversity, hospital or other
- Collaborators
- PNLUB, Ministère de la santé, Cotonou, République du Bénin., Laboratoire de Référence des Mycobactéries
- Study start
- Sep 2011
- Primary completion
- Dec 2016 (actual)
- Study completion
- Dec 2016 (actual)
- First posted
- 13 Sep 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
SUMMARY
Rationale: Buruli ulcer, caused by Mycobacterium ulcerans, is an ulcerative disease endemic in West Africa. It often leads to functional limitations. Treatment was by extensive surgery, until in 2005 gradually antibiotic treatment for eight weeks with rifampicin and streptomycin was added. Observation of Buruli ulcer lesions of limited size during antibiotic treatment showed that during treatment there is a paradoxical increase of the lesion, with a decrease of the lesion after week 14. Current WHO protocols advise to decide whether surgery is needed four weeks after the start of antibiotics. This might be too early in the healing process. The investigators hypothesize that delay in surgery is safe, and that it results in a reduction of the number of surgical interventions.
Objectives:
Primary Objective of this study is to compare the need for surgical treatment in standard timing of surgery at the end of eight weeks antimicrobial treatment with a policy to postpone surgical treatment until week 14.
Secondary Objectives are to study whether postponing surgery leads to less extensive surgery and a change in frequency of functional limitations;
Study design:
Patients will be randomized for surgery at week 8 after start of antibiotic treatment and week 14 after start of treatment. Reasons for treating doctors to decide to intervene with surgery will be according to current clinical practice and will be clearly defined in this protocol. Standard care of eight weeks of rifampicin and streptomycin will be given. All patients will be followed and lesional size using acetate sheet recordings will be used during follow-up.
Study population: Patients with a clinical picture of Buruli ulcer disease confirmed by diagnostic tests in the districts covered by the Buruli ulcer centers in Lalo and Allada, Benin. Patients who are pregnant, have a contraindication for general anaesthesia and children below three years old will be excluded. 130 Patients in each treatment arm will be included to detect a difference in percentage of patients needing surgery of 20 percent.
Main study parameters/endpoints: Primary outcome measure is the number of patients healed without surgery. Secondary outcome measures are the extent of surgery by measurement of lesional size, functional limitations after the end of treatment and one year after the start of treatment and the duration of admission.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| evaluation surgical intervention at week 8 | Other | Procedure: surgical intervention on Buruli ulcer |
| evaluation surgical intervention at week 14 | Other | Procedure: surgical intervention on Buruli ulcer |
Who may qualify
- Ages
- 3 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (2 listed)
- Patients with a clinical picture of Buruli ulcer disease in the districts covered by the Buruli ulcer centers in Lalo and Allada, Benin, will be included at start of antibiotic treatment.
- All stages of the disease will be included. Only patients with confirmed disease by direct microscopy following acid-fast staining or PCR will be included.
Key exclusion criteria (12 listed)
- Patients not on the standard treatment of eight weeks of rifampicin and streptomycin for any reason, will be excluded from this study.
- Treatment with macrolide or quinolone antibiotics, or antituberculous medication, or immune-modulatory drugs including corticosteroids within the previous one month.
- Patients not compliant with the antibiotic therapy will be excluded as well. Non-compliance is defined as the use of < 70 % of the prescribed antibiotics.
- Patients with a contraindication for general anaesthesia are not able to participate.
- Pregnancy.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| surgical intervention on Buruli ulcerCan the need for surgical intervention be avoided by delay of the decision on surgical intervention, comparing the need on surgical intervention from time points of week 8 and week 14 (number of weeks after start of antibiotic treatment with streptomycin/rifampicin). | Procedure or surgery | evaluation surgical intervention at week 14, evaluation surgical intervention at week 8 |
Primary outcome
Healing without surgical intervention
Time frame: one year
measurement of lesions at follow up visit, if lesion closed-> healed.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Jul 2019.
- Results publication: PubMed 29605498Wadagni AC, Barogui YT, Johnson RC, Sopoh GE, Affolabi D, van der Werf TS, de Zeeuw J, Kleinnijenhuis J, Stienstra Y. Delayed versus standard assessment for excision surgery in patients with Buruli ulcer in Benin: a randomised controlled trial. Lancet Infect Dis. 2018 Jun;18(6):650-656. doi: 10.1016/S1473-3099(18)30160-9. Epub 2018 Apr 5.
- Derived from this study: PubMed 27097163Barogui YT, Klis SA, Johnson RC, Phillips RO, van der Veer E, van Diemen C, van der Werf TS, Stienstra Y. Genetic Susceptibility and Predictors of Paradoxical Reactions in Buruli Ulcer. PLoS Negl Trop Dis. 2016 Apr 20;10(4):e0004594. doi: 10.1371/journal.pntd.0004594. eCollection 2016 Apr.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
D Agossadou, MD principal investigator
Program national lutte contre la lèpre et l'ulcère de Buruli, ministère de la santé, Hospital Lalo
G Sopoh, MD PhD principal investigator
Program national lutte contre la lèpre et l'ulcère de Buruli, Ministère de la Santé, Cotonou, Bénin, hospital Allada
Tjip S van der Werf, MD PhD principal investigator
UMCG - internal medicine/infectious diseases
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing surgical intervention on Buruli ulcer in people with Mycobacterium Ulcerans Disease and Buruli Ulcer, run by University Medical Center Groningen at 2 sites in Benin.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Jul 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Benin. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Healing without surgical intervention (time frame: one year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01432925, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Jul 2019.