Clinical trial NCT01192412: The CHIPS Trial (Control of Hypertension In Pregnancy Study)
Official title: The CHIPS Trial (Control of Hypertension In Pregnancy Study)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Gestational Hypertension
Keywords: hypertension
pregnancy
antihypertensive therapy
perinatal outcome
maternal outcome
Non-severe, non-proteinuric pre-existing or gestational hypertension in pregnancy
Lead sponsor: University of British Columbia
Sponsor class: OTHER
Collaborators: name: Canadian Institutes of Health Research (CIHR)
name: Sunnybrook Research Institute
First posted: 2010-09-01
Enrollment: 987
Sex: FEMALE
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The investigators do not know which approach to treatment of non-severe high blood pressure in pregnancy is better for women and babies.

In the CHIPS Trial, the investigators seek to determine whether 'less tight' control (aiming for a diastolic blood pressure \[dBP\] of 100 mmHg), compared with 'tight' control (aiming for a diastolic blood pressure \[dBP\] of 85 mmHg) can decrease the risks of adverse baby outcomes without increasing the risk of problems for the mother.

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:

1. Increase (or decrease) the likelihood of serious perinatal complications?
2. Increase (or decrease) the likelihood of severe hypertension and pre-eclampsia?
3. Increase (or decrease) the likelihood of maternal satisfaction with care?
4. 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.

Eligibility criteria: Inclusion Criteria:

1. Pre-existing or gestational hypertension (pre-existing hypertension is dBP greater than or equal to 90 mmHg before pregnancy or 20 weeks' gestation; gestational hypertension is dBP greater than or equal to 90 mmHg that develops after 20 weeks)
2. dBP of 90 - 105 mmHg if NOT TAKING antihypertensive therapy, or dBP of 85 - 105 mmHg if TAKING antihypertensive therapy
3. Live foetus (confirmed by Doptone assessment of foetal heart tones within one week before randomisation)
4. Gestational age 14 - 33+6 weeks (as measured by last menstrual period or dating ultrasound)

Exclusion Criteria:

1. Severe systolic hypertension (defined as a systolic blood pressure \[sBP\] greater than or equal to 160 mmHg at randomisation)
2. Proteinuria (defined as greater than or equal to 0.3 g/d by 24 hour urine collection, or if a 24 hour urine collection is not available, by a urinary protein:creatinine ratio of greater than or equal to 30 mg/mmol or urinary dipstick of greater than or equal to 2+)
3. Use of an angiotensin converting enzyme (ACE) inhibitor at greater than or equal to 14+0 weeks' gestation
4. Contraindication to either arm of the trial or to pregnancy prolongation
5. Known multiple gestation
6. Known lethal or major foetal anomaly
7. Plan to terminate pregnancy
8. Prior participation in CHIPS

Primary outcomes:
measure: Pregnancy Loss or NICU Admission for Greater Than 48 Hours
timeFrame: 6 weeks
Secondary outcomes:
measure: Serious Maternal Complications Measured up to 6 Weeks Postpartum
timeFrame: 6 weeks
Other outcomes:
Locations:
city: New Haven
country: United States
facility: Yale-New Haven Hospital
state: Connecticut
city: Louisville
country: United States
facility: Norton Hospital Downtown
state: Kentucky
city: Louisville
country: United States
facility: Norton Suburban Hospital
state: Kentucky
city: Boston
country: United States
facility: Beth Israel Deaconess
state: Massachusetts
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Camden
country: United States
facility: Cooper University Hospital
state: New Jersey
city: Chapel Hill
country: United States
facility: University of North Carolina
state: North Carolina
city: Greenville
country: United States
facility: East Carolina University
state: North Carolina
city: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Madison
country: United States
facility: Meriter Hospital
state: Wisconsin
city: Corrientes
country: Argentina
facility: Hospital JR Vidal
city: Mendoza
country: Argentina
facility: Hospital LC Lagomaggiore
city: Santa Fe
country: Argentina
facility: Hospital JM Cullen
city: Tucuman
country: Argentina
facility: Hospital Avellaneda
city: Campbelltown
country: Australia
facility: Campbelltown Hospital
state: New South Wales
city: Liverpool
country: Australia
facility: Liverpool Hospital
state: New South Wales
city: Adelaide
country: Australia
facility: Women's and Children's Hospital
city: Ipswich
country: Australia
facility: Ipswich Hospital
city: Subiaco
country: Australia
facility: King Edward Memorial Hospital
city: Subiaco
country: Australia
facility: St John of God Hospital
city: Goiania
country: Brazil
facility: Hospital Materno Infantil
city: Niteroi
country: Brazil
facility: Hospital Universitario Antonio Pedro
city: Porto Alegre
country: Brazil
facility: Hospital Sao Lucas - PUCRS
city: Rio de Janeiro
country: Brazil
facility: Maternidade Escola da UFRJ
city: Rio de Janerio
country: Brazil
facility: Clinica Perinatal Barra
city: Rio de Janerio
country: Brazil
facility: Laranjeiras Clinica Perinatal
city: Sao Paulo
country: Brazil
facility: Maternidade Escola de Vila Nova Cachoeirinha
city: Calgary
country: Canada
facility: Calgary Health Region - Foothills Hospital
state: Alberta
city: Edmonton
country: Canada
facility: Royal Alexandra Hospital
state: Alberta
city: Surrey
country: Canada
facility: Jim Pattison Outpatient Care and Surgery Centre
state: British Columbia
city: Vancouver
country: Canada
facility: University of British Columbia, Department of Obstetrics & Gynaecology
state: British Columbia
city: Vancouver
country: Canada
facility: Children's & Women's Health Centre of BC
state: British Columbia
city: Vancouver
country: Canada
facility: St Paul's Hospital
state: British Columbia
city: Winnipeg
country: Canada
facility: St Boniface General Hospital
state: Manitoba
city: St. John's
country: Canada
facility: Women's Health Centre
state: Newfoundland and Labrador
city: Halifax
country: Canada
facility: IWK Health Centre
state: Nova Scotia
city: London
country: Canada
facility: London Health Sciences Centre
state: Ontario
city: Ottawa
country: Canada
facility: Ottawa Hospital Civic Division
state: Ontario
city: Ottawa
country: Canada
facility: Ottawa Hospital General Division
state: Ontario
city: Toronto
country: Canada
facility: Mount Sinai Hospital
state: Ontario
city: Toronto
country: Canada
facility: St Michael's Hospital
state: Ontario
city: Toronto
country: Canada
facility: Sunnybrook Health Sciences Centre
state: Ontario
city: Toronto
country: Canada
facility: Toronto East General Hospital
state: Ontario
city: Montreal
country: Canada
facility: Hopital Sainte-Justine
state: Quebec
city: Montreal
country: Canada
facility: Royal Victoria Hospital
state: Quebec
city: Sherbrooke
country: Canada
facility: CHUS Fleurimont
state: Quebec
city: Saskatoon
country: Canada
facility: Royal University Hospital
state: Saskatchewan
city: Regina
country: Canada
facility: Regina General Hospital
city: Osorno
country: Chile
facility: Hospital Base Osorno
city: Puente Alto
country: Chile
facility: Hospital Dr Sotero del Rio
city: Cali
country: Colombia
facility: Clinica Materno Infantil Farallones
city: Cali
country: Colombia
facility: Clinica Versalles
city: Cali
country: Colombia
facility: Corporacion Conmfenalco Valle - Universidad Libre
city: Tartu
country: Estonia
facility: Tartu University Hospital-Women's Clinic
city: Debrecen
country: Hungary
facility: University of Debrecen
city: Bnei Brak
country: Israel
facility: Ma'ayney Hayeshua Medical Center
city: Hadera
country: Israel
facility: Hillel Yaffe Medical Center
city: Nazareth
country: Israel
facility: Nazareth Hospital (EMMS)
city: Amman
country: Jordan
facility: Islamic Hospital
city: 's-Hertogenbosch
country: Netherlands
facility: Jeroen Bosch Hospital
city: Almere
country: Netherlands
facility: Flevo ziekenhuis
city: Amersfoort
country: Netherlands
facility: Meander Medisch Centrum
city: Amsterdam
country: Netherlands
facility: Academic Medical Center
city: Amsterdam
country: Netherlands
facility: OLVG
city: Amsterdam
country: Netherlands
facility: VU Medical Center
city: Enschede
country: Netherlands
facility: Medisch Spectrum Twente
city: Groningen
country: Netherlands
facility: UMCG
city: Haarlem
country: Netherlands
facility: Kennemer Gasthuis Haarlem
city: Hilversum
country: Netherlands
facility: Tergooiziekenhuizen
city: Hoofddorp
country: Netherlands
facility: Spaarne Ziekenhuis
city: Maastricht
country: Netherlands
facility: MUMC Maastricht
city: Nieuwegein
country: Netherlands
facility: St Antonius Ziekenhuis
city: Oss
country: Netherlands
facility: Ziekenhuis Bernhoven
city: Utrecht
country: Netherlands
facility: Diakonessen Ziekenhuis
city: Utrecht
country: Netherlands
facility: UMCU
city: Veldhoven
country: Netherlands
facility: Maxima Medical Centre
city: Zwolle
country: Netherlands
facility: Isala Klinieken Zwolle
city: Auckland
country: New Zealand
facility: Waitemata Health-North Shore Hospital
city: Christchurch
country: New Zealand
facility: Christchurch Women's Hospital
city: Gdansk
country: Poland
facility: Medical University of Gdansk
city: Lodz
country: Poland
facility: Polish Mothers Memorial Hospital
city: Poznan
country: Poland
facility: University School of Medical Sciences
city: Basildon
country: United Kingdom
facility: Basildon & Thurrock University Hospital
city: Birmingham
country: United Kingdom
facility: Birmingham Women's Hospital
city: Blackburn
country: United Kingdom
facility: East Lancashire Hospitals NHS Trust
city: Bradford
country: United Kingdom
facility: Bradford Royal Infirmary
city: Chesterfield
country: United Kingdom
facility: Chesterfield Royal Hospital
city: Coventry
country: United Kingdom
facility: University Hospital Coventry and Warwickshire
city: Derby
country: United Kingdom
facility: The Royal Derby Hospital
city: Halifax
country: United Kingdom
facility: Calderdale Royal Hospital
city: Lancashire
country: United Kingdom
facility: Lancashire Teaching Hospitals NHS Foundation Trust
city: Lancaster
country: United Kingdom
facility: Royal Lancaster Infirmary
city: Leicester
country: United Kingdom
facility: Leicester Royal Infirmary
city: Liverpool
country: United Kingdom
facility: Liverpool Women's Hospital
city: London
country: United Kingdom
facility: Guy's & St Thomas' Hospital
city: London
country: United Kingdom
facility: Queen Elizabeth Hospital
city: Manchester
country: United Kingdom
facility: St Mary's Hospital
city: Newcastle upon Tyne
country: United Kingdom
facility: Royal Victoria Infirmary
city: Nottinghamshire
country: United Kingdom
facility: King's Mill Hospital
city: Nottingham
country: United Kingdom
facility: Nottingham City Hospital
city: Nottingham
country: United Kingdom
facility: Queen's Medical Centre
city: Ormskirk
country: United Kingdom
facility: Southport & Ormskirk Hospital
city: Plymouth
country: United Kingdom
facility: Derriford Hospital
city: Sheffield
country: United Kingdom
facility: Sheffield Teaching Hospitals NHS Foundation Trust
city: Slough
country: United Kingdom
facility: Wexham Park Hospital
city: Sunderland
country: United Kingdom
facility: City Hospitals Sunderland NHS Foundation Trust
city: Swansea
country: United Kingdom
facility: Singleton Hospital
city: Warwickshire
country: United Kingdom
facility: South Warwickshire NHS Trust
city: Wolverhampton
country: United Kingdom
facility: New Cross Hospital
city: York
country: United Kingdom
facility: York District Hospital
Study officials:
affiliation: The University of British Columbia
name: Laura A Magee, MD, FRCPC, MSc, FACP
role: PRINCIPAL_INVESTIGATOR
References:
citation: Magee LA, Singer J, Lee T, McManus RJ, Lay-Flurrie S, Rey E, Chappell LC, Myers J, Logan AG, von Dadelszen P. Are blood pressure level and variability related to pregnancy outcome? Analysis of control of hypertension in pregnancy study data. Pregnancy Hypertens. 2020 Jan;19:87-93. doi: 10.1016/j.preghy.2019.12.002. Epub 2020 Jan 9.
citation: Vidler M, Magee LA, von Dadelszen P, Rey E, Ross S, Asztalos E, Murphy KE, Menzies J, Sanchez J, Singer J, Gafni A, Gruslin A, Helewa M, Hutton E, Lee SK, Lee T, Logan AG, Ganzevoort W, Welch R, Thornton JG, Moutquin JM; CHIPS Study Group. Women's views and postpartum follow-up in the CHIPS Trial (Control of Hypertension in Pregnancy Study). Eur J Obstet Gynecol Reprod Biol. 2016 Nov;206:105-113. doi: 10.1016/j.ejogrb.2016.07.509. Epub 2016 Sep 10.
citation: Magee LA, von Dadelszen P, Singer J, Lee T, Rey E, Ross S, Asztalos E, Murphy KE, Menzies J, Sanchez J, Gafni A, Helewa M, Hutton E, Koren G, Lee SK, Logan AG, Ganzevoort W, Welch R, Thornton JG, Moutquin JM; CHIPS Study Group*. The CHIPS Randomized Controlled Trial (Control of Hypertension in Pregnancy Study): Is Severe Hypertension Just an Elevated Blood Pressure? Hypertension. 2016 Nov;68(5):1153-1159. doi: 10.1161/HYPERTENSIONAHA.116.07862. Epub 2016 Sep 12.
citation: Ahmed RJ, Gafni A, Hutton EK, Hu ZJ, Pullenayegum E, von Dadelszen P, Rey E, Ross S, Asztalos E, Murphy KE, Menzies J, Sanchez JJ, Ganzevoort W, Helewa M, Lee SK, Lee T, Logan AG, Moutquin JM, Singer J, Thornton JG, Welch R, Magee LA. The Cost Implications of Less Tight Versus Tight Control of Hypertension in Pregnancy (CHIPS Trial). Hypertension. 2016 Oct;68(4):1049-55. doi: 10.1161/HYPERTENSIONAHA.116.07466. Epub 2016 Aug 22.
citation: Magee LA, von Dadelszen P, Rey E, Ross S, Asztalos E, Murphy KE, Menzies J, Sanchez J, Singer J, Gafni A, Gruslin A, Helewa M, Hutton E, Lee SK, Lee T, Logan AG, Ganzevoort W, Welch R, Thornton JG, Moutquin JM. Less-tight versus tight control of hypertension in pregnancy. N Engl J Med. 2015 Jan 29;372(5):407-17. doi: 10.1056/NEJMoa1404595.