Prediction of short-term outcome in pregnant women with suspected preeclampsia study

Hypertensive disorders are the most common medical problem encountered in
pregnancy, affecting up to 15% of pregnancies and accounting for approximately
25% of antenatal admissions. Notably preeclampsia (PE) is a major cause of
maternal and fetal or neonatal mortality and morbidity. To date no treatment is
available to prevent PE or hinder at least progression of the disease. The
only causal therapy of PE is delivery. The etiology of this disease has not yet
been completely understood. Nevertheless, changes in circulating placental
angiogenic factors appear to play a key role in the pathogenesis of PE. Two
such angiogenic factors are sFlt-1 (Soluble Fms-like tyrosine kinase 1) and
PlGF (Placental Growth Factor). In patients with PE levels of sFlt-1 are
increased, wherease levels of PlGF are decreased. This results in a net
anti-angiogenic state causing endothelial dysfunction. Of note, sFlt-1
concentrations are high 5-6 weeks prior to onset of PE. Concentrations of PlGF
are also found to be low several weeks prior to clinical manifestation.
Increased levels of sFlt-1 and reduced levels of PlGF herald the onset of PE,
whereas the ratio of sFlt-1/PlGF, an index reflecting changes in both
biomarkers, is a better predictor of PE than either measure alone.

Primary objectives:
• To demonstrate that low ratios of sFlt-1/PlGF predict absence of PE /
eclampsia / HELLP (according to diagnostic criteria) within one week after
start visit (= Visit 1).
• To demonstrate that high ratios of sFlt-1/PlGF predict PE / eclampsia / HELLP
(according to diagnostic criteria) within four weeks after start visit (= Visit
1).

Secondary objectives:
• To collect evidence that low ratios of sFlt-1/PlGF correlate with absence of
PE-related adverse outcomes (other than PE / eclampsia / HELLP being part of
the primary objective) of the mother within one week after the start visit (=
Visit 1) as follows: maternal death, pulmonary edema, acute renal failure,
cerebral hemorrhage, cerebral thrombosis, DIC.
• To collect evidence that low ratios of sFlt-1/PlGF correlate with absence of
PE-related adverse outcomes of the fetus within one week after the start visit
(= Visit 1) as follows: perinatal/fetal death, delivery <34 weeks, IUGR,
placental abruption, respiratory distress, necrotizing enterocolitis,
intraventricular hemorrhage.
• To collect evidence that high ratios of sFlt-1/PlGF correlate with the
mother*s PE-related adverse outcomes (other than PE / eclampsia / HELLP being
part of the primary objective) within four weeks after start visit (= Visit 1)
as follows: maternal death, pulmonary edema, acute renal failure, cerebral
hemorrhage, cerebral thrombosis, DIC.
• To collect evidence that high ratios of sFlt-1/PlGF correlate with the fetus*
PE-related adverse outcomes within four weeks after start visit (= Visit 1) as
follows: perinatal/fetal death, delivery <34 weeks, IUGR, placental abruption,
respiratory distress, necrotizing enterocolitis, intraventricular hemorrhage.
• To evaluate sFlt-1 and PlGF values and the sFlt-1/PlGF ratio in diagnosed
cases of PE / eclampsia / HELLP in comparison to the corresponding parameters
in gestational age-matched controls.
• To collect evidence that an increase of the sFlt-1/PlGF ratio within one week
(Visit 1 to Visit 2; Visit 2 to Visit 3; Visit 3 to Visit 4; Visit 4 to Visit
5; including unscheduled visits) correlates with diagnosis of PE / eclampsia /
HELLP within four weeks after start visit.
• To correlate severity of PE with incremental changes of sFlt-1 and PlGF
values and sFlt-1/PlGF ratio, respectively, per time interval between visits
(sFlt-1/PlGF time course) within four weeks after start visit (= Visit 1).
• To correlate severity of PE with absolute values of sFlt-1, PlGF and
sFlt-1/PlGF ratio at diagnosis of PE.
• To collect evidence that high ratios of sFlt-1/PlGF correlate with preterm
delivery.
• To collect evidence that ratios of sFlt-1/PlGF correlate with time to
delivery.
• To investigate the economical benefit of considering the sFlt-1/PlGF ratio
for decision on the length of hospitalization of women with clinical suspicion
of PE and of the newborn.

PROGNOSIS is a Diagnostic Utility Study which is a multicenter, prospective,
double-blind, non-interventional study evaluating the short-term prediction of
preeclampsia / eclampsia / HELLP in pregnant women with suspected preeclampsia.

Risks Analysis:
Participation in the study is not afflicted with any risks, apart from the
general risks that arise when a blood sample is taken. Blood sampling will be
only performed with CE labeled sample collection devices. In rare cases
complications like extended bleeding, damage to nerves/arteries or infections
can happen. Urine-sample collection may give the patient a slight feeling of
discomfort.
The study is a non-interventional trial, medical care for the pregnant women
will be performed on the usual high medical standard at the study centre and
won*t be influenced by their study participation. Since the study design is
double-blind (neither the medical practitioner nor the study patient won*t
learn the results of the preeclampsia assay measurements) no medical decision
will be taken based on the diagnostics result of the preeclampsia assays. The
entire medical supervision and medical decisions remain in the responsibility
of the medical practitioner at the study site.

Benefits:
Even though there is no immediate clinical benefit for the study participants
from the scientific investigation, the scientific results gained from this
project will expand medical knowledge and will possibly contribute to improve
and to facilitate judgment about diagnosis and short-term prediction of
preeclampsia in the future.