Efficacy and safety of early target-controlled plasma volume replacement with a balanced gelatine solution versus a balanced electrolyte solution in patients with severe sepsis/septic shock: study protocol, design, and rationale of a prospective, randomized, controlled, double-blind, multicentric, international clinical trial

Table 1 GENIUS study flow diagram

Timepoint	Study period				Follow-up period
	Enrolment	Randomization	Post-randomization		Follow-up
	− 90 min	t = 0	Treatment phase, t = 0 to max. 48 h	Daily assessments, 48 h until ICU discharge or day 28	Day 28	Day 90
Enrolment:
Eligibility	x
Informed consent	x
Initial PLR manoeuvre	x
Randomization		x
Interventions:
IMP administration			x
Assessments:
Demographics and anamnesis^a
Demographic data		x
Anamnesis		x
Morbidity scores and temperature		x	x^b	x^b
Sepsis		x	x	x
Primary outcome parameter
Time to HDS			x
Safety parameters^a
Renal function		x^c	x	x
Coagulation		x	x	x
Hepatic function		x	x	x
Adverse Events			x	x
Need for blood products			x	x
Concomitant therapies/medication			x	x
Efficacy parameters^a
IMP and open-label medication			x
Crystalloids for further volume treatment			x	x
Fluid balance			x	x
Volume responsiveness			x
Haemodynamic parameters			x	x
Tissue oxygenation and acid-base balance		x^d	x	x
Clinical outcome parameters^a
Fulfilment of ICU discharge criteria			x	x
ICU/hospital LOS			Cumulative
Indication for RRT			Whenever applicable
Days on RRT			Cumulative
Infection/antibiotic-free days			Cumulative
Vasopressor-free days			Cumulative
Ventilator-free days			Cumulative
Study termination			Whenever applicable
Follow-up parameters^a
Colloid therapy^e					x
Last available serum creatinine (SCr)					x
Mortality, cause of death					x	x
Quality of life (QoL)^f						x
New RRT, kidney disease						x

^aA listing specifying the parameters determined is provided in section Methods/design, subsection Outcome measures
^bExcept Apache II
^cExcept urine output, need and indication for RRT
^dLactate only
^eDate and drug applied, retrospectively from ICU discharge until Day 28 or hospital discharge, whichever occurs first
^fTaking into account the patient population, the patients’ condition and the effort required to assess QoL, it was decided to collect data on QoL on Day 90 only

ISSN: 1745-6215