Condition category
Digestive System
Date applied
30/05/2004
Date assigned
21/07/2004
Last edited
02/02/2011
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

Contact information

Type

Scientific

Primary contact

Prof Gerhard E. Feurle

ORCID ID

Contact details

DRK-Krankenhaus Neuwied
Marktstr.104
Neuwied
56564
Germany

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

N/A

Study information

Scientific title

Acronym

SIMW

Study hypothesis

Whipple’s 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 Whipple’s 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bacteria to TW was tested in vitro; 95% of them were susceptible to meropenem and 70% were susceptible to ceftriaxion (unpublished, Maiwald et.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

http://www.drk-kh-neuwied.de.drktg.de/

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

  1. 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.

Additional files

Editorial Notes