Hydrocortisone plus fludrocortisone,
does it really help with Reduced 90-day mortality in adults with vasopressor-dependent septic shock?
research showsThe grade is B. APROCCHSS randomized and analyzed 1,241 participants. Ninety-day mortality was 264/614 (43.0%) with combination therapy versus 308/627 (49.1%) with placebo: an absolute reduction of 6.1 points, RR 0.88 (95% CI 0.78–0.99), and an approximate number needed to treat of 17. This is a large publicly funded mortality trial, but the exact combination lacks independent confirmatory replication, giving B with 76 points.
ads claimThis result concerns the specified seven-day two-steroid regimen in septic shock. It should not be generalized to hydrocortisone alone, other stages of shock, outpatient infection, or unsupervised long-term steroid use.
Useful facts when choosing a product
- Hydrocortisone 50 mg was given intravenously every six hours and fludrocortisone 50 micrograms once daily for seven days.
- The absolute 90-day mortality difference was -6.1 points, with an approximate number needed to treat of 17.
- The 10-point sample-size assumption was a detectable design value, not a validated minimum important threshold.
What the research actually shows
APROCCHSS was an investigator-led publicly funded trial in 34 French ICUs. Lilly supplied drotrecogin alfa for the original factorial component, which ended after market withdrawal; no company-provision statement was identified for the study products in the final steroid comparison.
Axis 6 B0 evidence ① Allocation concealment: "randomization was centralized through a secured Web site and used permutation blocks where size was not known" ② Blinding: "hospital staff, investigators, pharmacists and outcome assessors will remain blinded until public release of trial findings" ③ Analysis population and missing data: "Statistical analysis was planned to be performed in intent-to-treat"; "Missing data were not replaced." ④ Prespecified primary endpoint: "Primary endpoint was 90-day mortality rate." — consistent with registration NCT00625209
Why this is classified as B (76)
A large publicly funded double-blind placebo-controlled trial found a 6.1-point absolute mortality reduction and documented core safeguards, but lack of independent replication gives B with 76 points.
Counterpoint. The lower confidence-bound benefit was small and hyperglycemia increased, requiring patient selection and glucose monitoring.
Rejudgment record. Cross-check applied — Accounts for the 6.1-point mortality reduction in a 1,241-participant publicly funded double-blind placebo trial and the absence of independent replication
| Endpoint | H | Hard endpoint - actual events such as death |
| Replication | R1 | Single confirmatory trial |
| Independence | I2 | Decisive evidence is publicly or non-profit funded |
| Effect size | E+ | Meets the clinically important threshold |
The scoring table and the verdict agree (B).
Sub-claim grades by effect
This ingredient is marketed for several effects. A single overall grade blends strong and weak claims together, so each effect is graded separately here. The overall grade reflects the strongest disconfirming or core claim.
| Effect (sub-claim) | Grade | Basis |
|---|---|---|
| Reduced 90-day mortality | B | The absolute reduction was 6.1 points, RR 0.88. |
| Reduced serious adverse events | D | Overall serious adverse events were similar. |
Cross-check — Codex and Claude
Evidence Table
| Study | Design | Sample | Funding | Endpoint | Result | Weight |
|---|---|---|---|---|---|---|
| Study 1 | Double-blind randomized placebo-controlled superiority trial at 34 centers | 627 | French Ministry of Health contracts P090902 and P12-002-0030; initial approval P070128 | All-cause mortality at 90 days | 264/614 (43.0%) versus 308/627 (49.1%); absolute difference -6.1 points, RR 0.88 (95% CI 0.78–0.99), approximate NNT 17 | Single large publicly funded confirmatory mortality trial |
Receipt — 2 References
All 2 cited sources were verified for existence at the original page (as of 2026-08-18).
Reviewed and approved: Chamgap Editorial Team · Approval date: 2026-08-18 · Corrections: none
Cite this verdict
[Chamgap] Hydrocortisone plus fludrocortisone x 90-day mortality in septic shock — Evidence Grade B·76. 2 cited sources checked. Source: https://chamgap.com/en/verdicts/immunity/hydrocortisone-fludrocortisone-septic-shock-90-day-mortality/ · CC BY 4.0CC BY 4.0 — free to use with attribution; do not distort grades, numbers, or verdict meaning.
What this document does and does not do
Chamgap is an information source. It reports what research has and has not confirmed; it does not tell readers what to take or buy. That decision belongs to readers and, when needed, medical or legal professionals. This verdict reflects literature available up to the search date and may change as new research appears. Nothing here is medical advice.