MWD08

Charité - University medicine Berlin

Charitéplatz 1, Berlin, Germany, 10117

Prof. Dr. Dr. Thomas Schneider, Charité - University medicine Berlin CBF, Medical clinic I, infectious diseases, 0049 84452286, thomas.schneider@charite.de

Dr. Verena Moos, Charité - University medicine Berlin CBF, Medical clinic I, infectious diseases , 0049 450514383, verena.moos@charite.de

No

No

No

Final

27 Sep 2023

Yes

05 Nov 2020

Yes

05 Nov 2020

No

Whipple's disease is a fatal infection with Tropheryma (T.) whipplei if left untreated. The efficacy of antibiotics in the treatment of Whipple's disease has only been demonstrated in case series and in a study that has only been published as an abstract. The current treatment of Whipple's disease is therefore empirical, without an evidence-based foundation such as randomised controlled trials. The latter is a systematic problem due to the rarity of the disease. The rarity of the disease is also the reason why the drugs ceftriaxone, hydroxychloroquine, trimethoprim and sulfamethoxazole have not yet been approved. Here, we wanted to test the non-inferiority of oral antibiotic therapy alone for Whipple's disease compared to a combined therapy of intravenous induction therapy followed by oral maintenance therapy. Primary endpoint was clinical remission without relapse after 24 months (12 months of treatment and 12 months of follow-up).

Regulal follow up visits and the possibility for physicians and patients to contact the principle investigator at any time guaranteed safety of the subjects

26 May 2010

Yes

No

Germany: 60

60

60

0

0

0

0

0

0

43

17

0

overall trial (overall period)

Randomised - controlled

due to the different applications (iv and oral) blinding would have been a challenge.

Yes

Doxycycline

Tablet

Oral use

2x 100mg Doxycycline per day

Hydroxychloroquine

Quensyl

Tablet

Oral use

2x 200mg oral per day

Trimethoprim Sulfamethoxazol

Cotrim, Bactrim

Tablet

Oral use

In case of positive PCR from cerebrospinal fluid 5x oral Trimethoprim Sulfamethoxazol forte (800mg/160mg) per day till PCR-negativity

Cefriaxone

Rocephine, Cefotrix

Concentrate for solution for injection

Intravenous use

2g intravenously once a day for 14 days

Trimethoprim Sulfamethoxazol

Cotrim, Bactrim

Tablet

Oral use

2x oral Trimethoprim Sulfamethoxazol forte (800mg/160mg) per day for 12 months

arm B

arm A

arm B

arm A

The primary endpoint was clinical complete remission without recurrence during the observation period of 24 months, which required a value of ≤ 2 of a composite clinical score including WD-specific symptoms, C-reactive protein (CRP), and hemoglobin (Hb). Persistent WD-associated diseases, not indicative for a persistent infection (i.e. osteoarthritis) and irreversible neuronal damage acquired before diagnosis were not considered as treatment failure. Clinical remission was assumed at a score of 0-2, scores > 2 indicated failure of clinical remission.

Primary

24months

Composite outcome of complete clinical remission at 24 months. Point estimates and two-sided 95% confidence intervals are shown for the treatment effect, defined as the risk difference for complete remission between groups in the intention-to-treat (ITT) and per protocol (PP) analysis. The non-inferiority margin for doxycycline and hydroxychloroquine as compared with the combination of ceftriaxone and TMP-SMX was −18 percentage points. For ITT and PP analysis, the lower end of the two-sided 95%

arm B v arm A

52

Post-hoc

0

2-sided

24 months

9.1

Arm A intravenous

arm B oral-only