Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
N/A
Study information
Scientific title
Acronym
SIMW
Study hypothesis
Whipples Disease (WD) is a rare, infectious disorder (a member of the Orphanet group). Based on pathology records, its incidence in Germany is estimated to be about 0.4 per million. On this basis, it has been stated that clinical studies cannot be done because there are not enough individuals affected by Whipples disease.
Consequently, no prospective controlled trials are available. One retrospective analysis came to the conclusion that co-trimoxazole was more efficient than tetracycline in inducing and in maintaining remission of WD. However, cerebral involvement became evident during continuous treatment with co-trimoxazole in one patient. WD leads to death unless treated with antibiotics. As also in vitro antimicrobial susceptibility data are not yet available for the causative actinomycete Tropheryma Whipplei (TW), antibiotic therapy is empirical. There is no standard treatment for WD based on hard scientific evidence. Since a major problem of WD is cerebral involvement, it has been proposed that treatment should be initiated with high doses of intravenously applied antimicrobials known to penetrate into the central nervous system.
In a pilot study, antibiotic susceptibility of phylogenetically related bacteria to TW was tested in vitro; 95% of them were susceptible to meropenem and 70% were susceptible to ceftriaxion (unpublished, Maiwald et. al). A randomised comparison of meropenem and ceftriaxon in the treatment of bacterial meningitis showed no significant difference in efficacy.
In SIMW, therefore, these two antibiotics, both licensed for the treatment of severe infections and both known to penetrate into the central nervous system are compared in randomised order: ceftriaxon versus meropenem or imipenem.
Ethics approval
The SIMW trial was accepted by the Ethics Committee of the Landesärztekammer Mainz before the start of the trial.
Study design
Open label, parallel group, randomised controlled trial.
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Not specified
Trial type
Not Specified
Patient information sheet
Condition
Whipple's Disease
Intervention
Amended on 17/08/2007:
Intravenous ceftriaxon versus intravenous meropenem/imipenem, followed by 12 months of oral co-trimoxazole. Enrolment for these two arms was completed in December 2003.
A non-randomised third arm to SIMW (with additional 20 patients) was started in July 2004. The participants in the third arm receive intravenous ceftriaxone (as in the first arm of SIMW), followed by oral co-trimoxazole for three months (instead of 12 months). Otherwise the protocols are identical to the other two arms. The third arm, therefore, examines whether short-term oral treatment with co-trimoxazole is noninferior to 12 months oral treatment. This third arm without an own control group will be compared with the two arms of SIMW. The third arm was introduced in order to facilitate participant recruitment as Whipple's disease is very rare.
Dosages:
Ceftriaxone 2 g daily intravenously for 14 days (in the first arm of SIMW and in the third arm)
Meropenem 3 x 1 g daily intravenously for 14 days (in the second arm of SIMW)(In this intent to treat trial imipenem can be used instead of meropenem).
Co-trimoxazole contains 800 mg sulphamethoxazole plus 160 mg trimethoprim, and is administered twice daily perorally in all three arms (In both arms of SIMW for a year, in the third arm for three months).
Interventions provided at time of registration:
Randomized antibiotic treatment: ceftriaxon versus meropenem / imipenem.
In both arms this initial treatment is followed by 12 months of oral co-trimoxazole. Enrolment complete in December 2003. A non-randomised third arm to SIMW was started in July 2004. In this arm we will admit a maximum of 20 new patients until December 2006. This trial SIMW is organised under the premise that WD is a rare disease.
Intervention type
Drug
Phase
Not Specified
Drug names
ceftriaxon versus meropenem/imipenem
Primary outcome measures
Remission maintained for three years
Secondary outcome measures
Prospective collection of clinical, immunological, and pathological data concerning diagnosis and course of Whipple's disease.
Overall trial start date
01/01/1999
Overall trial end date
31/12/2006
Reason abandoned
Eligibility
Participant inclusion criteria
Patients with Whipple-typical macrophages in the duodenal mucosa or elsewhere confirmed by the reference pathologist
Participant type
Patient
Age group
Not Specified
Gender
Both
Target number of participants
42 for the first and second arms. As of 17/08/2007: Additional 20 participants for the third arm (total of 62).
Participant exclusion criteria
1. Current antimicrobial therapy for more than 1 month
2. Previous and unsuccessful antimicrobial therapy for Whipple's Disease
3. Recurrence of Whipple's Disease
4. Human Immunodeficiency Virus (HIV) infection, pregnancy, manifest tumor disease (except lymphoma)
Recruitment start date
01/01/1999
Recruitment end date
31/12/2006
Locations
Countries of recruitment
Austria, France, Germany, Switzerland
Trial participating centre
DRK-Krankenhaus Neuwied
Neuwied
56564
Germany
Sponsor information
Organisation
German Red Cross Hospital Neuwied (DRK Krankenhaus Neuwied)
Sponsor details
Marktstr.104
Neuwied
56564
Germany
+49 (0)2631/9814 01
g.e.feurle@t-online.de
Sponsor type
Hospital/treatment centre
Website
Funders
Funder type
Other
Funder name
German Red Cross Hospital Neuwied (DRK Krankenhaus Neuwied)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Funder name
The European Commission (ref: QLG1-CT-2002-01049)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Results - basic reporting
Publication summary
1. 2010 results in http://www.ncbi.nlm.nih.gov/pubmed/21135294
Publication citations
-
Results
Feurle GE, Moos V, Schinnerling K, Geelhaar A, Allers K, Biagi F, Bläker H, Moter A, Loddenkemper C, Jansen A, Schneider T, The immune reconstitution inflammatory syndrome in whipple disease: a cohort study., Ann. Intern. Med., 2010, 153, 11, 710-717, doi: 10.7326/0003-4819-153-11-201012070-00004.