Aggressive Versus Non-aggressive Goal-directed Fluid Resuscitation in Acute Pancreatitis
Status:
Recruiting
Trial end date:
2022-12-31
Target enrollment:
Participant gender:
Summary
WATERFALL is an investigator-initiated international multicenter open-label randomized
clinical trial comparing aggressive versus moderate fluid resuscitation in acute
pancreatitis. The main outcome variable will be the proportion of patients with
moderate-to-severe AP. Aggressive fluid resuscitation will consist in Lactated Ringer
Solution (LR) 20 ml/kg bolus (administered over 2 hours) followed by LR 3 ml/kg/h and
moderate a LR bolus 10 ml/kg in case of hypovolemia or no bolus in patients with normal
volemia, followed by LR 1.5 ml/kg/h. The patients will be assessed at 3 (±1), 12 (±4), 24
(±4), 48 (±4) and 72 (±4) hours from recruitment, and fluid resuscitation will be adjusted to
the patient´s clinical and analytical status according to a protocol. Subgroup analysis will
include patients with systemic inflammatory response syndrome (SIRS) at admission, with
persistent (>48h) SIRS and with hypovolemia at admission.
Based on available data (Sternby et al, Ann Surg 2019) we expect a 35% incidence of moderate
to severe AP in the moderate arm. Sample sizes of 372 per arm of treatment (744 patients)
achieve 80% power to detect a difference of 10% between the treatment arms at a significance
level (alpha) of 0.05 using a two-sided z-testNA, assuming a 10% dropout. These results
assume that 3 sequential tests are made using the O'Brien-Fleming spending function to
determine the test boundaries.
All analyses will be performed on an intention-to-treat basis. The trial could be stop early
for efficacy (primary end-point) if the observed two-sided P value is <0.0002 at the first
interim analysis (after 1/3 of patients have been enrolled) or is <0.012 at second interim
analysis (after 2/3 of patients have been enrolled), favoring aggressive fluid resuscitation.
At final analysis, the hypothesis that the incidence of moderate-to-severe pancreatitis is
similar in the two treatment arms will be rejected if p<0.046
Phase:
Phase 3
Details
Lead Sponsor:
Enrique de-Madaria
Collaborators:
Asociación Española de Gastroenterología Asociación Española de Pancreatología Instituto de Salud Carlos III