Trial document





This trial has been registered retrospectively.
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  DRKS00000389

Trial Description

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Title

Three-armed study for therapy of primary and secondary syphilis in HIV infection

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Trial Acronym

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URL of the Trial

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Brief Summary in Lay Language

The best therapy for syphilis (a sexually transmitted bacterial disease) in HIV infected patients is yet unknown. Treatment guidelines are different in the US and in Germany. Different antibiotic regimens are tested in this study. HIV-positive patients with early syphilis (stage I or II) can participate. They will be treated with ceftriaxon 1g i.v./10d (intravenous drip), benzathine penicillin 2x 1,2 Mio i.U. i.m. (intramuscular) day 1 or benzathine penicillin 2x1,2 Mio i.U. i.m. day 1, 8, 15. Tolerability and efficacy is examined after 3, 6 and 12 months. No differences between the treatment forms are expected.

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Brief Summary in Scientific Language

Background:
Since 2001 the incidence of syphilis in Germany is rising. In 2003 2932 new syphilis cases were registered, 500 (20%) more than 2002. The incidence rate of syphilis in 2003 was 3,6 cases per 100000 inhabitants. Mostly effected were men who have sex with men (76%) [1]. Ca. 15% of syphilis patients also have a HIV-infection, up to 80% of HIV-infected patients have syphilis antibodies.
Diagnostic Methods:
Basis diagnostic methods in syphilis/HIV-coinfected patients do not differ from HIV negative patients. For screening TPHA, VDRL or RPR are used. For confirmation VDRL-titration or IgG-FTA-ABS can be used. To evaluate treatment indication IgM-FTA-ABS and 19S-IgM-FTA-ABS can be helpful. Patients with positive 19S- IgM-FTA-abs or VDRL > 1:8 or titers rising more than 2 steps should be treated. [2].
Most HIV/syphilis coinfected patients show typical clinical symptoms and a normal serum reaction. Up to 40% of HIV patients with primary or secondary syphilis have upnormal cerebrospinal fluid findings. Cerebrospinal fluid puncture should be considered in all HIV/syphilis coinfected patients [3]. Serologic testing can be unreliable. False negative Results are seen in patients with inadequate antibody production.. The VDRL-test is not specific and can be false positive. Titers can stay high in spite of optimal treatment. FTA abs IgM and des VDRL should normalize within 6-24 months, TPHA can persist life long [2].
Clinical stages:
Clinical stages of syphilis do not differ in HIV-positive or HIV-negative patients. There are more atypical or severe courses in HIV-coinfection. Cases of early progression to tertiary or neurosyphilis have been described. Symptoms of several stages can be seen at the some time. Reactivation of an old syphilis is possible.
Therapy:
Penicillin is the standard treatment of all syphilis stages. Bactericidal effect is seen in peripheral serum concentration of > 0,03IU/ml, intrathecal of > 0,078IU/ml. Generation time of treponema pallidum is ca. 30 hours. Bactericidal concentrations should be achieved for at least.8 days.
According to the German guidelines first line treatment for early syphilis (Stadium I or II up to one year after time of infection) in coinfected patients is benzathine penicillin 2,4 Mio i.U. (e.g. Pendysin? 1,2 Mio) i.m. in weekly intervals for 3 weeks [4]. The CDC recommends single shot treatment with benzathine penicillin 2,4 Mio i.E. i.U.. This is discussed because of case reports of neurological complications and treatment failure [4, 5, 6]. Rolfs et al examined 541 patients with early syphilis, including 101 HIV-positive patients, that were treated with single shot benzathine penicillin. 18% were classified as treatment failure after 6 months. Failure rate was higher in HIV-patients [7]. In another trial asymptomatic HIV/syphilis coinfected patients were treated i.m. with ceftriaxone or benzylpenicillin procain. No significant difference was seen with response rates around 70% [8]. Dowell et al. saw response rates to intramusculär ceftriaxone in HIV-infected patients with latent syphilis or neurosyphilis of 65%, 9 patients were classified as treatment failure, one patient showed progressive neurological symptoms [9]. Marra showed response rates of 80% to intraveneous ceftriaxone in HIV patients with neurosyphilis [10] In this study HIV-positive patients with early syphilis (stage I or II) will be treated with ceftriaxone 1g i.v./10d, benzathine penicillin 2x 1,2 Mio i.U. i.m. day 1 or benzathine penicillin 2x1,2 Mio i.U. i.m. day 1, 8, 15. Tolerability and efficacy are examined after 3, 6 and 12 months.
References:
1. RKI (2004) Zur Situation bei wichtigen Infektionskrankheiten: Syphilis in Deutschland 2003 Epid Bull 40:339-348
2. RKI (2003) Praktische Empfehlungen zur Serodiagnostik der Syphilis (Ergebnisse einer Konsensuskonferenz des RKI und der DSTDG) Epidem Bull 25:191-192
3. Marra CM, Maxwell CL, Smith SL, Lukehart SA, Rompalo AM, Eaton M, Stoner BP, Augenbraun M, Barker DE, Corbett JJ, Zajackowski M, Raines C, Nerad J, Kee R, Barnett SH (2004) Cerebrospinal fluid abnormalities in patients with syphilis : association with clinical and laboratory features. J Infect Dis 189:369-376
4. Parkes R, Renton A, Meheus A, Laukamm-Josten U (2004) Review of current evidence and comparison of guidelines for effective syphilis treatment in Europe. Int J STD AIDS 15:73-88
5. Berry CD, Hooton TM, Collier A, Lukehart S (1987) Neurologic relapse after benzathine penicillin therapy for secondary syphilis in a patient with HIV infection. N Engl J Med 316:1587-1589
6. Myint M, Baschiri H, Harrington RD, Marra CM (2004) Relapse of secondary syphilis after benzathine penicillin G : molecular analysis. Sex Transm Dis 31:1956-199
7. Rolfs RT, Joesoef RM, Hendershot EF (1997) A randomised trial of enhanced therapy for early syphilis in patients with and without HIV infection. N Engl J Med 337:307-314
8. Smith NH, Musher DM, Huang DB, Rodriguez PS, Dowell ME, Ace W, White AC (2000) Response of HIV-infected patients with asymptomatic syphilis to intensive intramuscular therapy with ceftriaxone or procaine penicilline. Int J STD AIDS 15:328-332
9. Dowell ME, Ross pG, Musher DM, Cate TR, Baug RE (1992) Response of latent syphilis or neurosyphilis to ceftriaxone therapy in persons infected with human immunodeficiency virus. Am J Med 93:477-479
10. Marra CM Boutin P, McArthur JC, Hurwitz S, Simpson PA, Haslett JA, van der Horst C, Nevin T, Hook EW (2000) A pilot study evaluating ceftriaxone and penicillin G as treatment agents for neurosyphilis in human immunodeficiency virus-infected individuals. Clin Infect Dis 30:540-544

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Organizational Data

  •   DRKS00000389
  •   2010/05/25
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  •   yes
  •   Approved
  •   2326, Ethik-Kommission der Medizinischen Fakultät der Ruhr-Universität Bochum
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Secondary IDs

  •   U1111-1114-6421 
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Health Condition or Problem studied

  •   A53.9 -  Syphilis, unspecified
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Interventions/Observational Groups

  •   ceftriaxone 1g i.v. for 10 days
  •   Bezathine penicillin 2x1,2 Mio i.E. i.m. once
  •   benzathine penicillin 2x 1,2 Mio i.E. i.m. day 1, 8, 15
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Characteristics

  •   Interventional
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  •   Randomized controlled trial
  •   Open (masking not used)
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  •   Active control
  •   Treatment
  •   Parallel
  •   IV
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Primary Outcome

treatment failure defined as:
-retreatment or
-treatment with any antibiotic active against treponema pallidum or
-no reduction by 2 titer levels in VDRL or FTAabs19S IgM after 48 weeks

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Secondary Outcome

none

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Countries of Recruitment

  •   Germany
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Locations of Recruitment

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Recruitment

  •   Actual
  •   2004/08/03
  •   150
  •   Multicenter trial
  •   National
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Inclusion Criteria

  •   Both, male and female
  •   18   Years
  •   no maximum age
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Additional Inclusion Criteria

-HIV positive Patients with serologically proven early syphilis

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Exclusion Criteria

-known sensibilization agaist ß-lactam antibiotics
-patients that were treated within the last 48h with an agent that is active against treponema pallidum
-pregnant or lactating women
-patients with late syphilis (latent syphilis of unknown duration, tertiary syphilis or neuro syphilis

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Addresses

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    • St. Josef Hospital Interdisziplinäre Immunologische Ambulanz
    • Mr.  Prof. Dr.  Norbert H.  Brockmeyer 
    • Gudrunstr. 56
    • 44791  Bochum
    • Germany
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    • St. Josef Hospital Bochum Interdisziplinäre Immunologische Ambulanz
    • Ms.  Dr. med.  Anja  Potthoff 
    • Gudrunstr. 56
    • 44791  Bochum
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    • St. Josef Hospital Interdisziplinäre Immunologische Ambulanz
    • Ms.  Dr. med.  Anja  Potthoff 
    • Gudrunstr. 56
    • 44791  Bochum
    • Germany
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Sources of Monetary or Material Support

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    • St. Josef Hospital Bochum
    • Gudrunstr. 56
    • 44791  Bochum
    • Germany
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    •   0234/5090
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Status

  •   Recruiting complete, follow-up complete
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Trial Publications, Results and other Documents

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