Clinical trial NCT03995914: Depression and Major Adverse Events in Older Patients Who Undergo a Transcatheter Aortic Valve Implantation
Official title: Impact of Depression on 1-year Major Adverse Events in Patients Aged 75 or Older Who Undergo Transcatheter Aortic Valve Implantation (TAVIDEP)
Study type: OBSERVATIONAL
Overall status: WITHDRAWN
Conditions: Depression
Aortic Stenosis
Keywords: MACCEs
Major cardiac and cerebrovascular events
TAVI
Older
Lead sponsor: University Hospital, Montpellier
Sponsor class: OTHER
First posted: 2019-06-24
Enrollment: 0
Sex: ALL
Minimum age (years): 75
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients aged 75 years or older, admitted for TAVI for severe and symptomatic aortic stenosis

Brief summary: Depression, screened using the Geriatric Depression Scale (GDS) Short Form, has recently been found to be associated with a 3-fold increase in 1-year mortality after aortic valve replacement (AVR) in patients aged 70 or older. The main objective of the study is to evaluate whether the 1-year incidence of major adverse cardiac and cerebrovascular events (MACCEs), evaluated according to the valve academic research consortium 2 (VARC-2 criteria), in patients aged 75 or older who undergo a transcatheter aortic valve implantation (TAVI), should be similar in patients with depression systematically screened (using the 15-item GDS score), confirmed, and handled by a psychiatrist, and in patients without depression detected, after adjusting for frailty criteria and comorbidities.

Detailed description: * Setting: the University hospital of Montpellier and the Perpignan hospital (France)
* Study population: 300 patients undergoing a TAVI, recruited over a 2-year period and followed for 12 months.
* Measurements at baseline: depression systematically screened by the 15-item Geriatric Depression Scale before TAVI. If the score is 4 or higher, patients will be evaluated by a psychiatrist and the patient will be treated according to current guidelines. Other possible confounders of the relationship between depression and poor outcomes: age; Fried's frailty phenotype; short physical performance battery; comorbidities; disability in the activities of daily living (ADL) and instrumental activities of daily living (IADL); cognitive function (Mini Mental State Examination; Clock Test score; Montreal cognitive assessment).
* Measurements (by telephone): 30 days after TAVI: MACCEs and hospitalization stay duration; 6 and 12 months after TAVI: MACCEs, 15-item GDS, ADL and IADL, new medical problem since the last visit, hospital admission, death, compliance and adverse effects of antidepressant drugs if applicable.

In case of withdrawal, the investigator will perform all examinations scheduled for the final study visit, which includes recording of AEs. In any case, the patient will be treated in accordance with standard care in the Montpellier and Perpignan centers.

Our hypothesis is that 40% of patients aged 75 or older will meet the criteria for depression (1-2), and that the 12-month incidence of MACCEs will be of 25% in patients without depression and of 50% in patients with depression. Our assumption is that the treatment of depression will reduce by 50% the incidence of MACCEs, to reach comparable incidence (relative difference of 10% or less) as the incidence observed in patients without depression.

To test this hypothesis, the number of patients with depression is 110 and the number of patients without depression is 165 (Total: 275 patients) to have a power of 90%. Considering a loss to follow-up rate of 10%, 300 patients will be included in the present study.

-Population analysis : The data will be entered into an eCRF (Ennov clinical) allowing consistencies control and remote monitoring. The data will also be validated on site from the source data by the TEC of the study. All included subjects will be taken into account in the description of the population. Data will be analyzed under the responsibility of Marie-Christine PICOT (Epidemiology and clinical research unit of the Montpellier University Hospital) with SAS software version 9 (SAS Institute, Cary, N.C.).

The statistical analysis plan (SAP), covering all the analyses to be performed on all data, will be written before database lock. For all collected variables, descriptive statistics will be calculated according to the level of measurement. For metric variables, a check whether the data can be assumed normally distributed will be first conducted. For normally distributed variables, mean and standard deviation will be calculated. For skewed variables, median and range will be used. In case of categorical variables group proportions and contingency tables will be prepared.

A comparison of baseline parameters between patients with and without depression (age, gender, number of drugs taken, Fried's and Rockwood's frailty criteria, SPPB, TUG, HRQOL, ADL, IADL, MMSE, Clock-Drawing test, MOCA; lives alone or not) will be conducted.

The incidence of MACCEs and other endpoints (mortality, hospitalization and nursing home admission rate, ADL, IADL score) at 6 and 12 months after TAVI will be compared between patients screened and treated for depression and in patients without depression. All analyses will be performed before and after adjustment for parameters distinguishing patients with confirmed depression and without depression at baseline.

The efficacy of the treatment of depression started by the psychiatrist will be assessed by comparing the 15item GDS, CES-D, Lille Apathy rating scale, HRQOL at baseline and at 6 and 12 months. The AE of antidepressant drugs will be described, such as the rate of withdrawal.

If the incidence of MACCEs and other outcomes is comparable in both groups of patients, the present study will provide preliminary results in order to conduct a randomized control trial to demonstrate that the systematic screening of depression and its treatment can reduce the incidence of MACCEs in patients aged 75 or older who undergo a TAVI.

Eligibility criteria: Inclusion Criteria:

* Patients aged 75 years or older
* Patients eligible for TAVI and for study inclusion after a consensus decision of a multidisciplinary team including at least an interventional cardiologist, a cardiothoracic surgeon, a geriatrician, and an anesthetist.
* Subjects able to attend all scheduled visits and to comply with all trial procedures
* Subjects covered by public health insurance
* Signed informed

Exclusion Criteria:

* Subject unable to read or/and write
* Patients with emergency procedure, clinical instability (defined as unstable vital signs or refractory ongoing symptoms, acute decompensated heart failure)
* Patients with severe neuropsychiatric impairment
* Planned longer stay outside the region that prevents compliance with the visit plan
* Subject who are in a dependency or employment with the sponsor or the investigator
* Participation in another clinical trial within the last 4 weeks before the screening date

Primary outcomes:
measure: Number of Incidence of MACCEs
timeFrame: 1 year
Secondary outcomes:
measure: Number of Incidence of MACCEs
timeFrame: 1 and 6 months
measure: Number of Death
timeFrame: 6 and 12 months
measure: Number of hospitalization
timeFrame: 6 and 12 months
measure: Katz Index of Independence in Activities of Daily Living
timeFrame: 6 and 12 months
measure: The Lawton Instrumental Activities of Daily Living (IADL) Scale
timeFrame: 6 and 12 months
measure: Rate of depression
timeFrame: 1, 6 and 12 months
measure: Compliance of anti-depressant drugs prescribed
timeFrame: 1, 6 and 12 months
measure: Effects of anti-depressant drugs prescribed on the Health
timeFrame: 1, 6 and 12 months
Other outcomes:
Locations:
Study officials:
affiliation: University Hospital, Montpellier
name: hubert Blain, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Drudi LM, Ades M, Turkdogan S, Huynh C, Lauck S, Webb JG, Piazza N, Martucci G, Langlois Y, Perrault LP, Asgar AW, Labinaz M, Lamy A, Noiseux N, Peterson MD, Arora RC, Lindman BR, Bendayan M, Mancini R, Trnkus A, Kim DH, Popma JJ, Afilalo J. Association of Depression With Mortality in Older Adults Undergoing Transcatheter or Surgical Aortic Valve Replacement. JAMA Cardiol. 2018 Mar 1;3(3):191-197. doi: 10.1001/jamacardio.2017.5064.