UMIN-CTR Clinical Trial

Unique ID issued by UMIN UMIN000033986
Receipt number R000038744
Scientific Title Low dose amoxycillin versus amoxycillin and probenecid for syphilis in HIV patient: a randomised, open-label, non-inferiority trial
Date of disclosure of the study information 2018/09/03
Last modified on 2023/11/20 13:48:54

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Basic information

Public title

Low dose amoxycillin versus amoxycillin and probenecid for syphilis in HIV patient: a randomised, open-label, non-inferiority trial

Acronym

Low dose amoxycillin versus amoxycillin and probenecid for syphilis in HIV patient: a randomised, open-label, non-inferiority trial

Scientific Title

Low dose amoxycillin versus amoxycillin and probenecid for syphilis in HIV patient: a randomised, open-label, non-inferiority trial

Scientific Title:Acronym

Low dose amoxycillin versus amoxycillin and probenecid for syphilis in HIV patient: a randomised, open-label, non-inferiority trial

Region

Japan


Condition

Condition

Syphilis

Classification by specialty

Medicine in general Infectious disease Adult

Classification by malignancy

Others

Genomic information

NO


Objectives

Narrative objectives1

Investigate the efficacy and safety of low-dose amoxycillin versus amoxycillin and probenecid

Basic objectives2

Safety,Efficacy

Basic objectives -Others


Trial characteristics_1

Confirmatory

Trial characteristics_2

Pragmatic

Developmental phase

Not applicable


Assessment

Primary outcomes

Treatment success rate at one year after treatment

Key secondary outcomes

Treatment success rate at 3, 6, 9 months after treatment and adverse event rate


Base

Study type

Interventional


Study design

Basic design

Parallel

Randomization

Randomized

Randomization unit

Individual

Blinding

Open -no one is blinded

Control

Active

Stratification

YES

Dynamic allocation

NO

Institution consideration

Institution is not considered as adjustment factor.

Blocking

NO

Concealment

Central registration


Intervention

No. of arms

2

Purpose of intervention

Treatment

Type of intervention

Medicine

Interventions/Control_1

amoxycillin 500 mg orally three times a day
14 days for early syphilis(primary, secondary and early latent syphilis)
28 days for late syphilis(late latent syphilis and unknown duration of syphilis)

Interventions/Control_2

amoxycillin 1,000 mg orally three times a day and probenecid 250 mg orally three times a day
14 days for early syphilis(primary, secondary and early latent syphilis)
28 days for late syphilis(late latent syphilis and unknown duration of syphilis)

Interventions/Control_3


Interventions/Control_4


Interventions/Control_5


Interventions/Control_6


Interventions/Control_7


Interventions/Control_8


Interventions/Control_9


Interventions/Control_10



Eligibility

Age-lower limit

20 years-old <=

Age-upper limit


Not applicable

Gender

Male and Female

Key inclusion criteria

1) HIV patient
2) The diagnosis of syphilis was based on a) or b)
a) Serum rapid plasma regain(RPR) titers is 8 or greater and positive Treponema. Pallidum Hemagglutination(TPHA) result. When serum RPR titers is 8, the diagnosis of syphilis requires signs of syphilis like chancre or skin rash.
b) 4-fold or more rise in RPR titer from the individual's prior test

Key exclusion criteria

1) pregnant or breast feeding woman
2) a history of amoxycillin or probenecid allergy
3) otosyphilis, ocular syphilis or neurosyphilis diagnosed based on the findings of cerebrospinal fluid
4) patient who needs antibiotics other than the antibiotics we used in this study which is effective for syphilis at diagnosis
5)patient who started antibiotics within 3 weeks before diagnosis

Target sample size

112


Research contact person

Name of lead principal investigator

1st name Daisuke
Middle name
Last name Mizushima

Organization

National Center for Global Health and Medicine Hospital

Division name

AIDS Clinical Center

Zip code

1628655

Address

1-21-1, Toyama, Shinjuku-ku,Tokyo 162-8655, Japan

TEL

03-3202-7181

Email

dmizushi@acc.ncgm.go.jp


Public contact

Name of contact person

1st name Naokatsu
Middle name
Last name Ando

Organization

National Center for Global Health and Medicine Hospital

Division name

AIDS Clinical Center

Zip code

1628655

Address

1-21-1, Toyama, Shinjuku-ku,Tokyo 162-8655, Japan

TEL

03-3202-7181

Homepage URL


Email

nandou@hosp.ncgm.go.jp


Sponsor or person

Institute

self-finance

Institute

Department

Personal name



Funding Source

Organization

None

Organization

Division

Category of Funding Organization

Other

Nationality of Funding Organization



Other related organizations

Co-sponsor


Name of secondary funder(s)



IRB Contact (For public release)

Organization

Certified Review Board of National Center for Global Health and Medicine

Address

1-21-1 Toyama

Tel

03-3202-7181

Email

rinrijm@hosp.ncgm.go.jp


Secondary IDs

Secondary IDs

NO

Study ID_1


Org. issuing International ID_1


Study ID_2


Org. issuing International ID_2


IND to MHLW



Institutions

Institutions

国立国際医療研究センター病院(東京都)


Other administrative information

Date of disclosure of the study information

2018 Year 09 Month 03 Day


Related information

URL releasing protocol

https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000038744

Publication of results

Published


Result

URL related to results and publications

https://academic.oup.com/cid/article/77/5/779/7157181

Number of participants that the trial has enrolled

112

Results

A total of 112 participants were randomized into 2 groups. Serological cure rates within 12 months were 90.6% and 94.4% with the low-dose amoxicillin and combination regimens, respectively. Serological cure rates for early syphilis within 12 months were 93.5% and 97.9% with the low-dose amoxicillin and combination regimens, respectively. Non-inferiority of low-dose amoxicillin compared with amoxicillin plus probenecid overall and for early syphilis was not confirmed.

Results date posted

2023 Year 11 Month 20 Day

Results Delayed


Results Delay Reason


Date of the first journal publication of results

2023 Year 05 Month 09 Day

Baseline Characteristics

The baseline characteristics of the study participants were balanced between the groups. Regarding the syphilis stage, the proportion of participants with early syphilis was 86.6 percent, whereas that with late syphilis was 13.4 percent. At diagnosis, the median manual RPR titer was 64 (IQR 32-128), whereas the median automated RPR titer was 151.9 (IQR 58.8-345). Regarding HIV status, 91.1% of participants with HIV were on antiretroviral therapy, their median CD4 count was 525, and 94.6% of the PWH were virally suppressed.

Participant flow

Eligible participants were randomized in a one-to-one ratio to the combination of amoxicillin plus probenecid group or the low-dose amoxicillin group using a computer-generated random list. The block size of the randomization was four. The allocation was disclosed to the physician and patients. The laboratory technicians were unaware of participants' treatment allocations. Those assigned to the amoxicillin plus probenecid group received amoxicillin 1000 mg and probenecid 250 mg thrice daily, orally for 14 days for early and 28 days for late syphilis.
Alternatively, those assigned to the low-dose amoxicillin group received amoxicillin 500 mg thrice daily, orally for 14 days for early and 28 days for late syphilis.

Adverse events

In total, 21.4% of drug-related side effects were reported by study participants. Of those, 17.9% were reported for the low-dose regimen and 25.0% for the combination regimen. JH reactions occurred in 12.5% and 14.3% of participants on the low-dose and combination regimens, respectively. Drug rashes, nausea, and diarrhea occurred in 5.4%, 3.6%, and 0% of those on the low-dose regimen and 7.1%, 1.8%, and 5.4% of participants on the combination regimen, respectively. There were no significant differences between the groups for any of these safety variables. Based on the self-reported adherence, 93.8% of participants took more than 95% of the study drug.

Outcome measures

The primary outcome was the cumulative serological cure rate within 12 months after treatment determined with the conventional RPR card test. A serological cure was a 4-fold decrease or negative conversion in RPR titer. Secondary outcomes were serological cure rates within 3, 6, and 9 months after treatment using the conventional or automated RPR test and serological cure rates within 12 months after treatment using the automated RPR test. Safety was assessed via self-reported side effects. Participants were asked at the second visit after completing their regimen about drug-related side effects, such as diarrhea, nausea, vomiting, and drug allergy was defined as new systemic reactions such as fever and skin rash that appeared after 4 days of treatment initiation. They were also asked about JarischHerxheimer (JH) reactions, defined as systemic reactions such as fever, rashes, or myalgia within 2 days of starting treatment, except for anaphylactic reactions. Adherence to the study drugs was assessed through self-reporting.

Plan to share IPD

The data supporting this article are available on reasonable request from the corresponding author.

IPD sharing Plan description

The data supporting this article are available on reasonable request from the corresponding author.


Progress

Recruitment status

Completed

Date of protocol fixation

2018 Year 08 Month 13 Day

Date of IRB

2018 Year 08 Month 13 Day

Anticipated trial start date

2018 Year 09 Month 03 Day

Last follow-up date

2022 Year 02 Month 03 Day

Date of closure to data entry

2022 Year 02 Month 03 Day

Date trial data considered complete

2022 Year 03 Month 03 Day

Date analysis concluded

2022 Year 04 Month 03 Day


Other

Other related information



Management information

Registered date

2018 Year 09 Month 01 Day

Last modified on

2023 Year 11 Month 20 Day



Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000038744


Research Plan
Registered date File name

Research case data specifications
Registered date File name

Research case data
Registered date File name