Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT05310929 |
| Other study ID # |
FMASU R47/2019 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
August 28, 2019 |
| Est. completion date |
March 25, 2022 |
Study information
| Verified date |
March 2022 |
| Source |
Ain Shams University |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Two hundred patients with severe PE were admitted prepartum to the ICU to stabilize blood
pressure. They were randomly assigned to one of two groups (100 in each group): Group N
received nitroglycerine intravenous infusion in a concentration of 1 mg/ml, thus 1µg/Kg/min
equals to 4.8 ml/hr for an 80 Kg patient. Group L received labetalol intravenous infusion in
a concentration of 10 mg/ ml, thus 50 mg/ml equals to 5 ml/hr. The starting infusion rate of
the antihypertensive medication was 5 ml/hr. The infusion rate was titrated to stabilize
systolic blood pressure (SBP) at 130-140 mmHg and diastolic blood pressure (DBP) at 80-90
mmHg (study end point) by adjusting the infusion rate as required either by maintaining the
same infusion rate or by changing its infusion rate by 1 ml/hr up or down according to the
clinical condition every 10 minutes. On any abrupt reduction in blood pressure below 120 mmHg
for SBP or 80 mmHg for DBP, the infusion was immediately discontinued, and a bolus of 150 ml
lactate ringer was given.
Description:
Patients and Methods The study was conducted in the intensive care unit (ICU) of the
Obstetrics and Gynaecology Hospital of Ain-Shams University as a randomized, double-blind,
and placebo-controlled study on patients diagnosed with severe PE from July 2016 to June
2018. The study was approved by Ethical Research Committee at Ain Shams University (ethical
number FMASU R 47/2019) and all participants provided written informed consent.
Woman eligible for this study were aged between 18-40 years old at greater than 34 weeks of
gestation having severe PE without severe features (without imminence of eclampsia or
clinical manifestations of target organ damage, as per the ACOG criteria) (7). Severe PE was
diagnosed by severe hypertension (systolic blood pressure ≥160 mmHg or diastolic blood
pressure ≥110 mmHg, repeated measurement should be taken for confirmation no more than 15
minutes later), presence of clinically significant proteinuria (0.3 grams or more of protein
in 24-hour urine collection, or urinary protein/creatinine ratio of 30 or more)[8].
Exclusion criteria were patients with chronic hypertension, imminence of eclampsia, target
organ damage, active asthma and congestive heart failure. Patients with any known allergy to
one of the study drugs are also excluded.
Two hundred patients with severe PE were admitted prepartum to the ICU to stabilize blood
pressure. They were randomly assigned to one of two groups (100 in each group): Group N
received nitroglycerine intravenous infusion in a concentration of 1 mg/ml, thus 1µg/Kg/min
equals to 4.8 ml/hr for an 80 Kg patient. Group L received labetalol intravenous infusion in
a concentration of 10 mg/ ml, thus 50 mg/ml equals to 5 ml/hr. The starting infusion rate of
the antihypertensive medication was 5 ml/hr. The infusion rate was titrated to stabilize
systolic blood pressure (SBP) at 130-140 mmHg and diastolic blood pressure (DBP) at 80-90
mmHg (study end point) by adjusting the infusion rate as required either by maintaining the
same infusion rate or by changing its infusion rate by 1 ml/hr up or down according to the
clinical condition every 10 minutes. On any abrupt reduction in blood pressure below 120 mmHg
for SBP or 80 mmHg for DBP, the infusion was immediately discontinued, and a bolus of 150 ml
lactate ringer was given.
Randomization was attained by using orderly numbered, opaque sealed envelopes containing
computer-generated random allocations.
Patients received full intensive care treatment for PE according to the standard protocol of
the obstetric ICU of Ain-Shams University. All treatments were provided by physicians who
were not involved in the study including infusion of lactated Ringer solution at a starting
rate of 75 ml/hr and then adjusted according to the fluid balance, magnesium sulfate (4 gm IV
loading dose over a period of 10 minutes and 1 gm/hr IV infusion until 24 hours after
delivery as seizure prophylaxis, its dose was adjusted according to renal function) in
addition to antihypertensive medications according to the assigned group. The study solution
was stopped if maternal pulse reached less than 60 bpm or increased more than 110 bpm.
Vital signs were monitored at admission and until patients were discharged from the ICU using
ECG, pulse oximetry, continuous invasive arterial blood pressure monitoring through radial
artery, and an indwelling catheter for urine output assessment.
Assessment of fetal well-being was done before starting of the study in the form of
cardiotocography (CTG), modified biophysical profile, doppler US on umbilical artery, and
growth scan. In addition, continuous fetal heart rate monitoring was done by CTG during the
study time.
Severe persistent hypertension was considered when SBP was greater than 160 mmHg or DBP was
greater than 110 mmHg after the administration of maximum dose of allocated drug treatment;
20 ml/hr. Hence, patient was shifted to sodium nitroprusside infusion after 2 hours of
starting treatment with assigned drugs.
After stabilization of the patient and once the target BP was achieved, induction of labor
was started using 3 mg prostaglandin E2 (PGE2) vaginal tablet. It was to be repeated after 6
hours if needed. In case oxytocin was to be used, it was administered at least 6 hours apart
from PGE2 last dose.
If the patient was not eligible for induction of labor as in case of previous cesarean
delivery (CS), transverse lie of the fetus and other standard obstetrical indications, CS was
done at once. CS was also performed in case of failed induction of labor (no uterine
contractions nor cervical changes after 6mg of PGE2), fetal compromise, arrest of progress of
labor, arrest of cervical dilatation, arrest of fetal descent, and in case of moderate or
severe accidental hemorrhage.
The following data were recorded and included demographic characteristics, the time taken to
control blood pressure (time from starting infusion till reaching study end point), and
number of sudden attacks of hypotension (BP values below the desired level). In addition,
side effects of drugs such as tachycardia (HR>100 bpm), bradycardia HR<60 bpm) headache,
nausea/vomiting, hypotension, flushing, dizziness were recorded. The mode of delivery either
vaginal or caesarean section was also recorded. Fetal outcome regarding stillbirths (death in
utero at or after 20 weeks' gestation) and suspected fetal compromise by abnormal CTG
(continuous or progressive fetal bradycardia <100 bpm, reduced fetal heart rate variability
(<5 bpm) that last more than 90 minutes, atypical variable decelerations with over 50% of
contractions, late decelerations for >30 minutes, single prolonged decelerations for more
than 3 minutes, or sinusoidal pattern more than 10 minutes). 1 min Apgar score less than 7-
and 5-minutes Apgar score less than 7 were also recorded.
