Condition category
Digestive System
Date applied
Date assigned
Last edited
Retrospectively registered
Overall trial status
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

Contact information



Primary contact

Prof Gerhard E. Feurle


Contact details

DRK-Krankenhaus Neuwied

Additional identifiers

EudraCT number number

Protocol/serial number


Study information

Scientific title



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bacteria to TW was tested in vitro; 95% of them were susceptible to meropenem and 70% were susceptible to ceftriaxion (unpublished, Maiwald et.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


Secondary study design

Randomised controlled trial

Trial setting

Not specified

Trial type

Not Specified

Patient information sheet


Whipple's Disease


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.

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



Not Specified

Drug names

ceftriaxon versus meropenem/imipenem

Primary outcome measure

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


Overall trial end date


Reason abandoned (if study stopped)


Participant inclusion criteria

Patients with Whipple-typical macrophages in the duodenal mucosa or elsewhere confirmed by the reference pathologist

Participant type


Age group

Not Specified



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


Recruitment end date



Countries of recruitment

Austria, France, Germany, Switzerland

Trial participating centre

DRK-Krankenhaus Neuwied

Sponsor information


German Red Cross Hospital Neuwied (DRK Krankenhaus Neuwied)

Sponsor details

+49 (0)2631/9814 01

Sponsor type

Hospital/treatment centre



Funder type


Funder name

German Red Cross Hospital Neuwied (DRK Krankenhaus Neuwied)

Alternative name(s)

Funding Body Type

Funding Body Subtype


Funder name

The European Commission (ref: QLG1-CT-2002-01049)

Alternative name(s)

Funding Body Type

Funding Body Subtype


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

Basic results (scientific)

Publication list

1. 2010 results in

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