Aspirin versus placebo in twin pregnancies for preeclampsia prevention: A multicentre, randomised, double-blind, placebo-controlled trial (ASPRE-T)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Fundacion Para La Formacion E Investigacion Sanitaria De La Region De Murcia

Participant type

Patients

Age range

18-64 years

Gender

Female

Therapeutic area

Diseases [C] - Female Urogenital Diseases and Pregnancy Complications [C13]

Trial duration

23 Mar 2023 → ongoing

Decision date (initial)

2024-04-08

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2023-503698-40-00

EudraCT number

2019-003341-15

ISRCTN

ISRCTN86684235

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Prophylaxis

To determine the effect of low-dose aspirin on theincidence of preterm preeclampsiawith delivery <37 weeks’ gestation.

Secondary objectives 11

1. To determine the effect of low-dose aspirin on the incidence of (stratified according to chorionicity) in delivery with PE at <32 weeks, <34 weeks, <37 weeks and at any gestation.
2. To determine the effect of low-dose aspirin on the incidence of (stratified according to chorionicity) in features of severe PE including: stroke, eclamspia, systolic blood pressure >160 mmHg on at least one occasion, diastolic blood pressure >110 mmHg on at least one occasion, respiratory failure requiring intubation or mechanical ventilation , myocardial ischemia or infarction, pulmonary edema, hepatic dysfunction (INR >1.2 in the absence of DIC), hepatic hematoma or rapture platelet count <100 x 109/litre, abnormal liver function enzymes (ALT or AST >67 iu/litre), acute kidney injury, creatinine >150 μmol/L, cortical blindness, retinal detachment, transfusion of any blood products, HELLP syndrome, placental abruption, postpartum hemorrhage (defined as blood loss ≥1 L within the first 24 hours after birth), intensive therapy or high-dependency unit admission, confirmed sepsis (positive blood or urine cultures) up to post-natal discharge and total number of nights in hospital.
3. To determine the effect of low-dose aspirin on the incidence of (stratified according to chorionicity) in gestational hypertension (GH).
4. To determine the effect of low-dose aspirin on the incidence of (stratified according to chorionicity) in birth at <32 weeks, <34 weeks and <37 weeks (Spontaneous, Iatrogenic for PE, GH or FGR or Iatrogenic for other reason).
5. To determine the effect of low-dose aspirin on the incidence of (stratified according to chorionicity) in death of one twin and / or both twins before discharge from hospital: o Miscarriage of the whole pregnancy or death of one twin <24 weeks’ gestation. o Stillbirth or neonatal death of one or both twins at <32 weeks, <34 weeks, <37 weeks and at any gestation.
6. To determine the effect of low-dose aspirin on the incidence of (stratified according to chorionicity) in birthweight <3rd, <5th and <10th percentile for gestational age.
7. To determine the effect of low-dose aspirin on the incidence of (stratified according to chorionicity) in placental abruption (clinically or on placental examination) at <32 weeks, <34 weeks, <37 weeks and at any gestation.
8. To determine the effect of low-dose aspirin on the incidence of (stratified according to chorionicity) in postpartum hemorrhage (defined as blood loss ≥1 L within the first 24 hours after birth).
9. To determine the effect of low-dose aspirin on the incidence of (stratified according to chorionicity) in neonatal morbidity.
10. To determine the effect of low-dose aspirin on the incidence of (stratified according to chorionicity) in neonatal therapy: Neonatal intensive care unit admission. Ventilation defined as need of positive pressure: o (continuous positive airway pressure (CPAP) or nasal continuous positive airway pressure (NCPAP)) or intubation. o Composite of any of the above.
11. To determine the effect of low-dose aspirin on the incidence of (stratified according to chorionicity) in length of stay in neonatal intensive care unit.

Conditions and MedDRA coding

Preeclampsia

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. Age > 18 years.
2. DCDA or MCDA twin pregnancies.
3. Both live fetuses at 11+2-13+6 weeks of gestation.
4. Informed and written consent.

Exclusion criteria 14

1. Monoamniotic twins.
2. Triplet pregnancies that had undergone embryo reduction to twins or with one vanishing twin.
3. Pregnancies complicated by major fetal abnormality or nuchal translucency thickness >3.5 mm identified at the 11+2-13+6 weeks scan.
4. MCDA twin pregnancies in which there are early signs of TTTS or sFGR defined by a 20% discordance in CRL at the 11+2-13+6 weeks’ scan.
5. Those who lack capacity and who are unable to provide informed consent to take part.
6. Women taking low-dose aspirin regularly (administration must have ceased >7 days prior to randomization).
7. Participation in another drug trial within the previous 7 days.
8. Haemorrhagic diathesis; coagulation disorders such as haemophilia and thrombocytopenia or concurrent anticoagulant therapy.
9. Active or history of recurrent peptic ulceration and/or gastric/intestinal haemorrhage, or other kinds of bleeding such as cerebrovascular haemorrhages.
10. Patients who are suffering from known gout, severe hepatic impairment or severe renal impairment.
11. Hypersensitivity to salicylic acid compounds or prostaglandin synthetase inhibitors (e.g. certain asthma patients who may suffer an attack or faint and certain patients who may suffer from bronchospasm, rhinitis and urticaria) or to any excipients (see section 6.1 of the SmPC for details).
12. Patients on long term non-steroidal anti-inflammatory medication.
13. Not fluent in local language and absence of interpreter.
14. Any other reason the clinical investigators think will prevent the potential participant from complying with the trial protocol.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. To determine if the prophylactic use of low-dose aspirin from the first-trimester of pregnancy in women with twin pregnancy can reduce the incidence of PE with delivery <37 weeks’ gestation.

Secondary endpoints 12

1. To determine the effect of low-dose aspirin on the incidence of (stratified according to chorionicity): Delivery with PE at <32 weeks, <34 weeks, <37 weeks and at any gestation.
2. Gestational hypertension (GH)
3. Birth at <32 weeks, <34 weeks and <37 weeks (Spontaneous, Iatrogenic for PE, GH or FGR, Iatrogenic for other reason).
4. Death of one twin and / or both twins before discharge from hospital: Miscarriage of the whole pregnancy or death of one twin <24 weeks’ gestation, Stillbirth or neonatal death of one or both twins at <32 weeks, <34 weeks, <37 weeks and at any gestation.
5. Birthweight <3rd, <5th and <10th percentile for gestational age
6. Placental abruption (clinically or on placental examination) at <32 weeks, <34 weeks, <37 weeks and at any gestation.
7. Postpartum hemorrhage (defined as blood loss ≥1 L within the first 24 hours after birth)
8. Neonatal morbidity: Intraventricular hemorrhage (IVH) grade II or above : Grade II – IVH occupies <50% of the lateral ventricle volume. Grade III – IVH occupies ≥50% of the lateral ventricle volume. Grade IV – Hemorrhagic infarction in periventricular white matter ipsilateral to a large IVH. Neonatal sepsis. Encephalopathy grade. Neonatal seizures. Anemia. Respiratory distress. Necrotizing enterocolitis requiring surgical intervention. Composite of any of the above.
9. Neonatal therapy: Neonatal intensive care unit admission, Ventilation defined as need of positive pressure (continuous positive airway pressure (CPAP) or nasal continuous positive airway pressure (NCPAP) or intubation, Length of stay in neonatal intensive care unit o composite of any of the above
10. Features of severe PE including: Stroke, Eclampsia, systolic blood pressure >160 mmHg on at least one occasion, diastolic blood pressure >110 mmHg on at least one occasion, respiratory failure requiring intubation or mechanical ventilation, myocardial ischemia or infarction, pulmonary edema, hepatic dysfuncion, hepatic hematoma or rapture, platelet count <100 x 109/litre
11. Features of severe PE including: abnormal liver function enzymes (ALT or AST >67 iu/litre), acute kidney injury, creatinine >150 μmol/L, cortical blindness, retinal detachment, transfusion of any blood products, HELLP syndrome, placental abruption, postpartum hemorrhage (defined as blood loss ≥1 L within the first 24 hours after birth), intensive therapy or high-dependency unit admission.
12. Features of severe PE including: confirmed sepsis (positive blood or urine cultures) up to post-natal discharge, total number of nights in hospital.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Fundacion Para La Formacion E Investigacion Sanitaria De La Region De Murcia

Sponsor organisation

Fundacion Para La Formacion E Investigacion Sanitaria De La Region De Murcia

Address

Carretera De Cartagena S/n, El Palmar El Palmar

City

Murcia

Postcode

30120

Country

Spain

Scientific contact point

Organisation

Fundacion Para La Formacion E Investigacion Sanitaria De La Region De Murcia

Contact name

Catalina de Paco Matallana

Public contact point

Organisation

Fundacion Para La Formacion E Investigacion Sanitaria De La Region De Murcia

Contact name

Catalina de Paco Matallana

Locations

7 EU/EEA countries · 19 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 39 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

17 submissions — initial application plus substantial / non-substantial modifications