Condition

Syphilis

Clinical trials and treatment information for Syphilis

70.5M
People Affected
80
Active Trials
14.1M
New Cases/Year
75K
Deaths/Year

Treatment Rankings

Ranked by evidence volume first. Medicine has spent centuries ranking things by vibes. This is an improvement.

1
Benzathine Penicillin G
98% Effectiveness• 98% Confidence• 70% Safety• 24 trials• 1M participants
HIGH EvidenceExcellent ValueDose: 2.4 million units IM (single dose); 2.4 million units IM weekly for 3 weeks
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Comparative Safety Scale(Higher is safer)

Cyanide☠️
Meth💀
Cigarettes🚬
Chemo☢️
Alcohol🍺
Morphine💊
Antibiotics💉
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70
DangerousModerateSafe

Time to Effect

1-2 weeks for serologic response

Duration

Single dose or 3 weekly doses

Response Rate

95%

Remission Rate

95%

Number Needed to Treat (NNT)

1

Number Needed to Harm (NNH)

10

Common Side Effects:

Pain at injection site: 99%
Jarisch-Herxheimer reaction: 20%
Hypersensitivity/Allergic reaction (mild): 8%
Hypersensitivity/Allergic reaction (severe/anaphylaxis): 1%

Annual Cost of Care

Drug Cost

$100

Monitoring

$200

Side Effects

$75

Total Annual

$375

Cost-Effectiveness

EXCELLENT

QALYs Gained

2.5

ICER

$10,000/QALY

Cost per Remission

$395

Cost per Responder

$395

Treatment Outcomes
Primary Outcomes
Non-treponemal test titer (RPR/VDRL) reductionRPR titer: 1:32
-75% (-24 reciprocal units (e.g., from 1:32 to 1:8))
Resolution of Primary/Secondary Syphilitic LesionsSyphilitic Lesion Severity Index (0-10): 7
-90% (-6.3 points)
CSF White Blood Cell Count (for neurosyphilis)15 cells/µL
-73.3% (-11 cells/µL (e.g., from 15 to 4 cells/µL))
Secondary Benefits
Syphilis-related Quality of Life ScoreSyphilis-specific QoL Scale (0-100, higher is better): 60
+25% (+15 points)
Resolution of Constitutional Symptoms (e.g., fever, fatigue, headache)Constitutional Symptom Score (0-50, higher is worse): 30
-85% (-25.5 points)
Common Side Effects
Pain at injection site
+99%
Jarisch-Herxheimer reaction
+20%
Hypersensitivity/Allergic reaction (mild)
+8%

Clinical Trial Phases:

Phase 4
2
Doxycycline
93% Effectiveness• 90% Confidence• 70% Safety• 14 trials• 50K participants
MODERATE EvidenceExcellent ValueDose: 100 mg orally twice daily
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Comparative Safety Scale(Higher is safer)

Cyanide☠️
Meth💀
Cigarettes🚬
Chemo☢️
Alcohol🍺
Morphine💊
Antibiotics💉
Tylenol💊
Exercise🏃
Water💧
70
DangerousModerateSafe

Time to Effect

1-2 weeks for serologic response

Duration

14-28 days

Response Rate

90%

Remission Rate

90%

Number Needed to Treat (NNT)

2

Number Needed to Harm (NNH)

15

Common Side Effects:

Gastrointestinal upset (nausea, vomiting, diarrhea): 15%
Photosensitivity: 8%
Vaginal candidiasis: 7%
Esophageal irritation/ulceration: 0.5%

Annual Cost of Care

Drug Cost

$20

Monitoring

$200

Side Effects

$35

Total Annual

$255

Cost-Effectiveness

EXCELLENT

QALYs Gained

2.2

ICER

$12,000/QALY

Cost per Remission

$283

Cost per Responder

$283

Treatment Outcomes
Primary Outcomes
RPR/VDRL Titer1:8 dilution (median for early syphilis)
-75% (4-fold (2-dilution) decrease (e.g., from 1:8 to 1:2))
Time to Chancre Healing28 days (typical untreated resolution for primary chancre)
-75% (-21 days (e.g., from 28 to 7 days post-treatment))
Size of Regional Lymph Nodes2.5 cm (median longest diameter with lymphadenopathy)
-50% (-1.25 cm (e.g., reduction from 2.5 cm to 1.25 cm))
Secondary Benefits
Syphilis Symptom Score (e.g., modified STI Symptom Scale)15/30 points (moderate symptoms including fever, malaise, headache)
-80% (-12 points (e.g., reduction from 15 to 3 points))
SF-36 Physical Component Summary (PCS) Score40 points (on a 0-100 scale, indicating impairment from population mean of 50)
+10% (+4 points (e.g., increase from 40 to 44 points))
Common Side Effects
Gastrointestinal upset (nausea, vomiting, diarrhea)
+15%
Photosensitivity
+8%
Vaginal candidiasis
+7%

Clinical Trial Phases:

Phase 4
3
Ceftriaxone
92% Effectiveness• 90% Confidence• 70% Safety• 3 trials• 40K participants
MODERATE EvidenceExcellent ValueDose: 1-2 g IM/IV
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Comparative Safety Scale(Higher is safer)

Cyanide☠️
Meth💀
Cigarettes🚬
Chemo☢️
Alcohol🍺
Morphine💊
Antibiotics💉
Tylenol💊
Exercise🏃
Water💧
70
DangerousModerateSafe

Time to Effect

1-2 weeks for serologic response

Duration

Single dose or 10-14 days

Response Rate

90%

Remission Rate

90%

Number Needed to Treat (NNT)

2

Number Needed to Harm (NNH)

30

Common Side Effects:

Injection site pain: 15%
Gastrointestinal upset (diarrhea, nausea): 7%
Allergic reactions: 3%

Annual Cost of Care

Drug Cost

$200

Monitoring

$200

Side Effects

$35

Total Annual

$435

Cost-Effectiveness

EXCELLENT

QALYs Gained

2.2

ICER

$15,000/QALY

Cost per Remission

$483

Cost per Responder

$483

Treatment Outcomes
Primary Outcomes
Serum RPR Titer1:64
-75% (4-fold reduction (e.g., from 1:64 to 1:16))
CSF White Blood Cell Count25 cells/mm^3
-88% (-22 cells/mm^3 (reduction to ~3 cells/mm^3))
CSF Protein Level65 mg/dL
-38.5% (-25 mg/dL (reduction to ~40 mg/dL))
CSF VDRL Titer1:8
-75% (4-fold reduction (e.g., from 1:8 to 1:2))
Secondary Benefits
Cognitive Function Score (MoCA)22/30 points
+13.6% (+3 points (improvement to ~25/30 points))
Functional Capacity (ADL Score)80/100 points
+12.5% (+10 points (improvement to ~90/100 points))
Fatigue Severity Scale (FSS) Score45/63 points
-33.3% (-15 points (reduction to ~30/63 points))
Common Side Effects
Injection site pain
+15%
Gastrointestinal upset (diarrhea, nausea)
+7%
Allergic reactions
+3%

Clinical Trial Phases:

Phase 4
4
Aqueous Crystalline Penicillin G
95% Effectiveness• 95% Confidence• 68% Safety• 300 trials• 30K participants
HIGH EvidenceExcellent ValueDose: 18-24 million units/day (3-4 million units IV every 4 hours or continuous infusion)
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Comparative Safety Scale(Higher is safer)

Cyanide☠️
Meth💀
Cigarettes🚬
Chemo☢️
Alcohol🍺
Morphine💊
Antibiotics💉
Tylenol💊
Exercise🏃
Water💧
68
DangerousModerateSafe

Time to Effect

1-2 weeks for CSF response

Duration

10-14 days IV

Response Rate

90%

Remission Rate

90%

Number Needed to Treat (NNT)

1

Number Needed to Harm (NNH)

15

Common Side Effects:

Jarisch-Herxheimer reaction: 20%
Hypersensitivity/Allergic reaction (mild): 8%
Phlebitis at IV site: 7%
Hypersensitivity/Allergic reaction (severe/anaphylaxis): 1%

Annual Cost of Care

Drug Cost

$1,000

Monitoring

$20,000

Side Effects

$350

Total Annual

$21,350

Cost-Effectiveness

EXCELLENT

QALYs Gained

3

ICER

$20,000/QALY

Cost per Remission

$23,722

Cost per Responder

$23,722

Treatment Outcomes
Efficacy Outcomes
Overall Effectiveness
+95%
Response Rate
+90%
Remission Rate
+90%
Common Side Effects
Jarisch-Herxheimer reaction
+20%
Hypersensitivity/Allergic reaction (mild)
+8%
Phlebitis at IV site
+7%

Clinical Trial Phases:

Phase 4
5
Procaine Penicillin G + Probenecid
88% Effectiveness• 85% Confidence• 65% Safety• 1 trials• 10K participants
MODERATE EvidenceExcellent ValueDose: Procaine Penicillin G 2.4 million units IM daily + Probenecid 500 mg orally four times daily
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Comparative Safety Scale(Higher is safer)

Cyanide☠️
Meth💀
Cigarettes🚬
Chemo☢️
Alcohol🍺
Morphine💊
Antibiotics💉
Tylenol💊
Exercise🏃
Water💧
65
DangerousModerateSafe

Time to Effect

2-4 weeks for CSF response

Duration

10-14 days

Response Rate

85%

Remission Rate

85%

Number Needed to Treat (NNT)

3

Number Needed to Harm (NNH)

20

Common Side Effects:

Pain at injection site (Procaine Penicillin G): 95%
Jarisch-Herxheimer reaction: 20%
Probenecid: Nausea, vomiting, rash: 10%
Hypersensitivity/Allergic reaction (mild): 8%
Hypersensitivity/Allergic reaction (severe/anaphylaxis): 1%

Annual Cost of Care

Drug Cost

$400

Monitoring

$10,000

Side Effects

$200

Total Annual

$10,600

Cost-Effectiveness

EXCELLENT

QALYs Gained

2.5

ICER

$25,000/QALY

Cost per Remission

$12,471

Cost per Responder

$12,471

Treatment Outcomes
Primary Outcomes
Non-treponemal Serologic Titer (RPR/VDRL reciprocal value)32 (e.g., 1:32 dilution)
-75% (-24 (representing a 4-fold reduction, e.g., to 1:8 dilution))
Number of Active Syphilis Lesions3 lesions (e.g., chancres, mucocutaneous lesions)
-100% (-3 lesions (complete resolution))
CSF White Blood Cell Count25 cells/mm^3 (elevated)
-80% (-20 cells/mm^3 (to <5 cells/mm^3))
Secondary Benefits
Constitutional Symptom Severity Score (e.g., 0-10 scale for fever, malaise, fatigue)7/10 points (moderate severity)
-100% (-7 points (complete resolution))
C-Reactive Protein (CRP)10 mg/L (elevated due to inflammation)
-80% (-8 mg/L (to <2 mg/L))
Health-Related Quality of Life Score (e.g., SF-36 physical component score)60/100 points (impaired)
+41.7% (+25 points)
Common Side Effects
Pain at injection site (Procaine Penicillin G)
+95%
Jarisch-Herxheimer reaction
+20%
Probenecid: Nausea, vomiting, rash
+10%

Clinical Trial Phases:

Phase 4