The CHIPS Trial (Control of Hypertension In Pregnancy Study) | NCT01192412

NCT01192412

ID	Type	Description	Link
MCT-87522	Other Grant/Funding Number	CIHR
07-3431	Other Identifier	UBC

Status Module

Name	Class
Canadian Institutes of Health Research (CIHR)	OTHER_GOV
Sunnybrook Research Institute	OTHER

Description Module

Detailed Description

Primary research question:

For pregnant women with non-severe, non-proteinuric maternal hypertension at 14-33 weeks, will 'less tight' control (target diastolic blood pressure [dBP] of 100 mmHg) versus 'tight' control (target dBP of 85 mmHg) increase (or decrease) the likelihood of pregnancy loss or Neonatal Intensive Care Unit (NICU) admission for greater than 48 hours?

Secondary research question:

Will 'less tight' versus 'tight' control increase (or decrease) the likelihood of serious maternal complications?

Other research questions:

Will 'less tight' versus 'tight' control:

Increase (or decrease) the likelihood of serious perinatal complications?
Increase (or decrease) the likelihood of severe hypertension and pre-eclampsia?
Increase (or decrease) the likelihood of maternal satisfaction with care?
Result in significant changes in dBP or health care costs?

Treatment Allocation:

Eligible women will be randomised centrally to either 'less tight' control (aiming for dBP of 100mmHg) or 'tight' control (aiming for dBP of 85mmHg) of their hypertension.

Randomisation will be stratified by centre and type of hypertension (pre-existing or gestational).

In the 'less tight' control group, if dBP is ≥105mmHg, then antihypertensive medication must be started or increased in dose.
In the 'tight' control group, if dBP is ≤80mmHg, then antihypertensive medication must be decreased in dose or discontinued.
In both groups, centres will provide their usual care. Data will be collected on potential co-interventions (e.g., hospitalisation, bedrest).

Outcomes:

Primary: Pregnancy loss (miscarriage or ectopic pregnancy, pregnancy termination, stillbirth, or neonatal death) or high level neonatal care for >48 hours in the first 28 days of life or prior to primary hospital discharge, whichever is later.

Secondary: One/more serious maternal complication(s) until six weeks postpartum.

Follow-up:

Compliance (dBP and antihypertensive dose) will be assessed within 4 weeks of randomisation. Outcome data will be collected during the woman's (and baby's) hospital stay for birth (or loss). Women will be contacted 6 to 12 weeks after delivery (or loss) and, for preterm babies, when the baby is at 36 weeks corrected gestational age to enquire about satisfaction with care and any major maternal/neonatal morbidity following hospital discharge.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
'Less tight' control.	Active Comparator	The diastolic blood pressure (dBP) treatment goal is 100 mmHg.	Procedure: Intervention is blood pressure management approach
'Tight' control.	Active Comparator	The diastolic blood pressure (dBP) treatment goal is 85 mmHg.	Procedure: Intervention is blood pressure management approach.

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Intervention is blood pressure management approach	Procedure	1) 'Less tight' control. The dBP treatment goal is 100 mmHg. For safety, if dBP is >105 mmHg, then antihypertensive medication must be started or increased in dose. For dBP <100 mmHg, antihypertensive therapy should be decreased in dose or stopped, as appropriate. The intervention will be applied until delivery.

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Pregnancy Loss or NICU Admission for Greater Than 48 Hours	Pregnancy loss or NICU admission for greater than 48 hours, as recorded in the maternal and infant medical records immediately following the birth (or pregnancy loss), and then again after the mothers' and infants' discharge home. Supplemental information, about potential post-discharge maternal or neonatal morbidities in the 6 weeks following birth for the mother, or 28 days of life for the baby, will be obtained by contacting women at 6 weeks postpartum and/or from medical records.	6 weeks

Secondary Outcomes

Measure	Description	Time Frame
Serious Maternal Complications Measured up to 6 Weeks Postpartum	Serious maternal complications measured up to 6 weeks postpartum. Death or one or more life-threatening maternal complications: Adverse neurological complications (stroke, eclampsia, and/or blindness), and/or End-organ failure (uncontrolled hypertension, inotropic support, pulmonary oedema, respiratory failure, myocardial ischaemia/infarction, renal failure, coagulopathy, and/or transfusion)

Eligibility Module

Name	Affiliation	Role
Laura A Magee, MD, FRCPC, MSc, FACP	The University of British Columbia	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
Yale-New Haven Hospital		New Haven	Connecticut		United States
Norton Hospital Downtown

PubMed Identifier	Type	Citation	Retractions
36750953	Derived	Metcalfe RK, Harrison M, Singer J, Lewisch M, Lee T, von Dadelszen P, Magee LA, Bansback N; CHIPS Study Group. Using a patient-centred composite endpoint in a secondary analysis of the Control of Hypertension in Pregnancy Study (CHIPS) Trial. Trials. 2023 Feb 7;24(1):99. doi: 10.1186/s13063-023-07118-1.
31927325	Derived

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	'Less Tight' Control.	The diastolic blood pressure (dBP) treatment goal is 100 mmHg. Intervention is blood pressure management approach: 1) 'Less tight' control. The dBP treatment goal is 100 mmHg. For safety, if dBP is >105 mmHg, then antihypertensive medication must be started or increased in dose. For dBP <100 mmHg, antihypertensive therapy should be decreased in dose or stopped, as appropriate. The intervention will be applied until delivery.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Arm/Group Information

ID	Title	Description
BG000	'Less Tight' Control.	The diastolic blood pressure (dBP) treatment goal is 100 mmHg. Intervention is blood pressure management approach: 1) 'Less tight' control. The dBP treatment goal is 100 mmHg. For safety, if dBP is >105 mmHg, then antihypertensive medication must be started or increased in dose. For dBP <100 mmHg, antihypertensive therapy should be decreased in dose or stopped, as appropriate. The intervention will be applied until delivery.
BG001	'Tight' Control.	The diastolic blood pressure (dBP) treatment goal is 85 mmHg. Intervention is blood pressure management approach.: 'Tight' control. The dBP treatment goal is 85 mmHg. For safety, if dBP is <80 mmHg, then antihypertensive medication must be decreased in dose or discontinued. If dBP is >85 mmHg, then antihypertensive therapy should be started or increased in dose. The intervention will be applied until delivery.
BG002	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	BG00034.0± 5.7 BG00133.7± 5.8 BG00233.8± 5.8

Gender

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG000497 BG001490 BG002

Body-mass index

Available in 493 women in 'Less-tight' control, and 485 women in 'Tight' control

Number

participants

Title

Denominators

Categories

<18.5 kg/m^2

Title	Measurements
	BG0001 BG0012 BG002

Cigarette smoking during this pregnancy

Number

participants

Title

Denominators

Categories

Title	Measurements
	BG00035 BG00128 BG002

Nulliparous

Women who were never pregnant before (i.e., first pregnancy)

Number

participants

Title

Denominators

Categories

Title	Measurements
	BG000161 BG001168 BG002

Weeks of gestation

Mean

Standard Deviation

weeks

Title

Denominators

Categories

Title	Measurements
	BG00023.7± 6.3 BG00124.2± 6.3 BG002

Type of nonproteinuric hypertension

Number

participants

Title

Denominators

Categories

Preexisting hypertension

Title	Measurements
	BG000371 BG001365 BG002

Prior blood pressure ≥160 mm Hg systolic or ≥110 mm Hg diastolic during this pregnancy

Number

participants

Title

Denominators

Categories

Title	Measurements
	BG00082 BG00159 BG002

Antihypertensive medication at enrollment

Number

participants

Title

Denominators

Categories

Title	Measurements
	BG000279 BG001287 BG002

Blood pressure within 1 wk before randomization

Mean

Standard Deviation

mmHg

Title

Denominators

Categories

Systolic

Title	Measurements
	BG000140.4± 9.7 BG001139.7± 9.8 BG002

Currently monitoring blood pressure at home

Number

participants

Title

Denominators

Categories

Title	Measurements
	BG000185 BG001194 BG002

Gestational diabetes at enrollment

Number

participants

Title

Denominators

Categories

Title	Measurements
	BG00032 BG00131 BG002

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Pregnancy Loss or NICU Admission for Greater Than 48 Hours

Pregnancy loss or NICU admission for greater than 48 hours, as recorded in the maternal and infant medical records immediately following the birth (or pregnancy loss), and then again after the mothers' and infants' discharge home. Supplemental information, about potential post-discharge maternal or neonatal morbidities in the 6 weeks following birth for the mother, or 28 days of life for the baby, will be obtained by contacting women at 6 weeks postpartum and/or from medical records.

Posted

Number

participants

6 weeks

ID	Title	Description
OG000	'Less Tight' Control.	The diastolic blood pressure (dBP) treatment goal is 100 mmHg. Intervention is blood pressure management approach: 1) 'Less tight' control. The dBP treatment goal is 100 mmHg. For safety, if dBP is >105 mmHg, then antihypertensive medication must be started or increased in dose. For dBP <100 mmHg, antihypertensive therapy should be decreased in dose or stopped, as appropriate. The intervention will be applied until delivery.
OG001	'Tight' Control.	The diastolic blood pressure (dBP) treatment goal is 85 mmHg. Intervention is blood pressure management approach.: 'Tight' control. The dBP treatment goal is 85 mmHg. For safety, if dBP is <80 mmHg, then antihypertensive medication must be decreased in dose or discontinued. If dBP is >85 mmHg, then antihypertensive therapy should be started or increased in dose. The intervention will be applied until delivery.

Units	Counts
Participants	OG000493 OG001488

Title

Denominators

Categories

Title	Measurements
	OG000155 OG001150

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	We estimated that with a sample size of 514 per group, the study would have 80% power, at a two-tailed alpha level of 0.05, assuming primary outcome rates of 33% in the tight-control group and 25% in the less-tight-control group, a 10% rate of crossover, a 1% loss to follow-up, and two interim analyses, as calculated with the chi-square test with the use of East software (Cytel) and the Lan-DeMets spending function with O'Brien-Fleming-type boundaries for early stopping.					Odds Ratio (OR)	1.02			2-Sided	95	0.77	1.35				No	Superiority or Other

Secondary

Serious Maternal Complications Measured up to 6 Weeks Postpartum

Serious maternal complications measured up to 6 weeks postpartum. Death or one or more life-threatening maternal complications:

Adverse neurological complications (stroke, eclampsia, and/or blindness), and/or
End-organ failure (uncontrolled hypertension, inotropic support, pulmonary oedema, respiratory failure, myocardial ischaemia/infarction, renal failure, coagulopathy, and/or transfusion)

Posted

Number

participants

6 weeks

ID	Title	Description
OG000	'Less Tight' Control.	The diastolic blood pressure (dBP) treatment goal is 100 mmHg. Intervention is blood pressure management approach: 1) 'Less tight' control. The dBP treatment goal is 100 mmHg. For safety, if dBP is >105 mmHg, then antihypertensive medication must be started or increased in dose. For dBP <100 mmHg, antihypertensive therapy should be decreased in dose or stopped, as appropriate. The intervention will be applied until delivery.
OG001	'Tight' Control.	The diastolic blood pressure (dBP) treatment goal is 85 mmHg. Intervention is blood pressure management approach.: 'Tight' control. The dBP treatment goal is 85 mmHg. For safety, if dBP is <80 mmHg, then antihypertensive medication must be decreased in dose or discontinued. If dBP is >85 mmHg, then antihypertensive therapy should be started or increased in dose. The intervention will be applied until delivery.

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	'Less Tight' Control.	The diastolic blood pressure (dBP) treatment goal is 100 mmHg. Intervention is blood pressure management approach: 1) 'Less tight' control. The dBP treatment goal is 100 mmHg. For safety, if dBP is >105 mmHg, then antihypertensive medication must be started or increased in dose. For dBP <100 mmHg, antihypertensive therapy should be decreased in dose or stopped, as appropriate. The intervention will be applied until delivery.			155	493	241	493
EG001	'Tight' Control.	The diastolic blood pressure (dBP) treatment goal is 85 mmHg. Intervention is blood pressure management approach.: 'Tight' control. The dBP treatment goal is 85 mmHg. For safety, if dBP is <80 mmHg, then antihypertensive medication must be decreased in dose or discontinued. If dBP is >85 mmHg, then antihypertensive therapy should be started or increased in dose. The intervention will be applied until delivery.			150	488	223	488

Serious Adverse Events

Term	Organ System	Statistical Information
Pregnancy loss	Pregnancy, puerperium and perinatal conditions	EG00015 affected493 at risk EG00115 affected488 at risk
Miscarriage	Pregnancy, puerperium and perinatal conditions	EG0000 affected493 at risk EG0011 affected488 at risk
Ectopic pregnancy	Pregnancy, puerperium and perinatal conditions	EG0000 affected493 at risk EG0010 affected488 at risk
Elective termination	Pregnancy, puerperium and perinatal conditions	EG0001 affected493 at risk EG0011 affected488 at risk
Perinatal death	Pregnancy, puerperium and perinatal conditions	EG00014 affected493 at risk EG00111 affected488 at risk
Stillbirth	Pregnancy, puerperium and perinatal conditions	EG00012 affected493 at risk EG0017 affected488 at risk
Neonatal death	Pregnancy, puerperium and perinatal conditions	EG0002 affected493 at risk EG0014 affected488 at risk
High-level neonatal care for >48hr	Pregnancy, puerperium and perinatal conditions	EG000141 affected480 at risk EG001139 affected479 at risk
Birthweight <10th percentile	Pregnancy, puerperium and perinatal conditions	EG00079 affected491 at risk EG00196 affected488 at risk
Birthweight <3rd percentile	Pregnancy, puerperium and perinatal conditions	EG00023 affected491 at risk EG00126 affected488 at risk
Uncontrolled hypertension	Cardiac disorders	EG0000 affected493 at risk EG0010 affected488 at risk
Transient ischemic attack or stroke	Nervous system disorders	EG0000 affected493 at risk EG0011 affected488 at risk
Pulmonary edema	Respiratory, thoracic and mediastinal disorders	EG0002 affected493 at risk EG0011 affected488 at risk
Renal failure	Renal and urinary disorders	EG0000 affected493 at risk EG0011 affected488 at risk
Transfusion	Blood and lymphatic system disorders	EG00016 affected493 at risk EG0018 affected488 at risk

ID	Term
D011248	Pregnancy Complications
D005261	Female Urogenital Diseases and Pregnancy Complications
D000091642	Urogenital Diseases
D014652	Vascular Diseases
D002318	Cardiovascular Diseases

Term	Organ System	Statistical Information
Placental abruption	Pregnancy, puerperium and perinatal conditions	EG00011 affected493 at risk EG00111 affected488 at risk
Severe hypertension	Cardiac disorders	EG000200 affected493 at risk EG001134 affected488 at risk
Preeclampsia	Pregnancy, puerperium and perinatal conditions	EG000241 affected493 at risk EG001223 affected488 at risk