Enhanced External Counterpulsation to Treat Long COVID-19 Fatigue

NCT ID: NCT05668039

Last Updated: 2023-11-30

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

32 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-04-01

Study Completion Date

2024-07-31

Brief Summary

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The goal of this double blind, outcome-assessor blind, randomized controlled trial, is to compare the effectiveness of external encounter counterpulsation (EECP) versus sham procedure in participants with long COVID-19 fatigue.

The main question\[s\] it aims to answer are:

* Whether EECP improves fatigue score
* Whether EECP improves quality of life, six-minute walk test, and endothelial function Participants will attend 15 sessions (1-hour each) of EECP during 5 weeks Researchers will compare EECP versus sham procedure for the above outcomes.

Detailed Description

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Participants of this trial will be patients recovering from acute COVID-19, 3-12 months following the acute infection, and suffering from fatigue with a Patient-Reported Outcomes Measurement System (PROMIS)-Fatigue short-form (SF)-7a score of \> 50.

Exclusion criteria will include contra-indications for EECP (see protocl). Intervention, comparisn and outcomes are described above. Study plan: participants will be invited using social media, after filling a fatigue score (PROMIS) to test for eligibility. Those with a score of \> 50 will be invited for a study visit.

Study visit 1 will include informed consent, followed by physician interview, physical examination, ECG; and will be referred for completion of blood tests including complete blood count (CBC) to rule out significant anemia (Hb\< 12 for men or hb \<10 for women) and serum beta human chorionic gonadotrophin (bHCG).

Eligible patients will then be randomized into two groups for treatment with EECP vs sham procedure. In study Visit 2 they will answer several questionnaires, perforn EndoPAT test to assess endothelial dysfunction, and six-minute walk test, followed by either:

1. Treatment group- 1 hour EECP session
2. Sham group - 1 hour of a sham EECP session (patients will be hooked to the EECP device but it will be set to the lowest setting, and lowest frequency, therefore unable to create a sufficient rise in diastolic return). This visit will be followed by 3 times weekly 1 hour sessions for 5 weeks (15 sessions) of either EECP or sham procdeure, according to randomization group.

Questionnaire that will be used before and after the intervention will include:

1. Fatigue evaluation using the PROMIS 7a form, attached in appendix (as validated on Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS)patients)
2. Functional capacity evaluation using the Duke Activity Status Assessment (DASI) (https://www.mdcalc.com/duke-activity-status-index-dasi);
3. Shortness of Breath using the modified Medical Research Council dyspnea scale
4. Quality of life using the SF-36 questionnaire. 6mwt and endothelial dysfunction by EndoPAT will be held following the last treatment.

Study Visit 3 (3 months following starting treatment) will be a final Interview to assess improvement by questionnaires, as well as time to return to activity and time to return to work.

Conditions

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Post-Acute COVID-19 Syndrome

Keywords

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long COVID Enhanced eXternal counterpulsation

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Double blind, outcome assossor blind, randomized controlled trial
Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Investigators Outcome Assessors
Masking of participants - the sham procedure includes the same location of pneumatic blood-pressure cuffs used for the intervention; and will be perfoemd in the same frequency and duration as the intervention. Participants will be invited for the procedures at separate times to avoid connection between them.

Masking of investigator and outcome assessor - unblinded nurses and one unblinded physician will be responsible for performing the procedures (either intervention or sham), without involving other team members (other investigators or outcome assessors), who would remain blinded to the treatment arm.

Study Groups

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Enhanced external counterpulsation

Enhanced external counterpulsation (EECP/ECPT) is a non-invasive technique used to improve cardiac and cerebral perfusion. It aims to achieve 'diastolic augmentation' by increasing arterial blood pressure and retrograde aortic blood flow during diastole. This technique is currently used to treat refractory angina and heart failure, and was demonstrated to be well tolerated without limiting side effect. Practially, blood pressure cuffs are put along the lower limbs and are inflated to 300 mmHg pressure intermittently during one hour session. 15 sessions will be performed over 15 weeks.

Group Type EXPERIMENTAL

Enhanced external counterpulsation

Intervention Type PROCEDURE

15 one-hour sessions during 15 weeks of enhanced external counterpulsation.

Sham procedure

The procedure will be identical to the experimental procedure, excluding the pressure that will reach only 80 mmHg.

Group Type SHAM_COMPARATOR

Enhanced external counterpulsation

Intervention Type PROCEDURE

15 one-hour sessions during 15 weeks of enhanced external counterpulsation.

Interventions

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Enhanced external counterpulsation

15 one-hour sessions during 15 weeks of enhanced external counterpulsation.

Intervention Type PROCEDURE

Eligibility Criteria

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Inclusion Criteria

* Patients recovering from PCR or lateral flow testing proven acute COVID-19
* 3-12 months following the acute infection
* Suffering from fatigue with a PROMIS-SF-7a T-score of \> 50

Exclusion Criteria

* Acute decompensated heart failure
* Recent myocardial infarction within the last 3 months
* Unstable angina pectoris
* Severe hypertension \> 180/110 mm Hg
* Coagulopathy with international normalized ratio of prothrombin time \> 2.0
* Moderate to severe aortic regurgitation
* Abdominal aortic aneurysm (\>5 mm) or dissection
* Arrhythmias that may interfere with triggering of EECP system (uncontrolled atrial fibrillation, flutter and very frequent premature ventricular contractions)
* Heart rate of \<35 or \>125 beats per minute
* Any surgical intervention within 6 weeks before EECP
* Recent cardiac catheterization (1-2 weeks) or arterial femoral puncture
* Severe peripheral arterial disease
* Severe venous disease (thrombophlebitis, prior or current deep vein thrombosis or pulmonary embolism)
* Severe chronic obstructive pulmonary disease
* Pregnancy or women of childbearing age who do not have a negative pregnancy test
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Sheba Medical Center

OTHER_GOV

Sponsor Role lead

Responsible Party

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Prof. Dafna Yahav

Head, Infectious Diseases Unit

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Dana Yelin, MD

Role: PRINCIPAL_INVESTIGATOR

Sheba Medical Center

Locations

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Sheba medical center

Ramat Gan, , Israel

Site Status RECRUITING

Countries

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Israel

Central Contacts

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Dafna Yahav, MD

Role: CONTACT

Phone: 972548866488

Email: [email protected]

Dana Yelin, MD

Role: CONTACT

Phone: 972545383536

Email: [email protected]

Facility Contacts

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Dana Yelin, MD

Role: primary

References

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Michelen M, Manoharan L, Elkheir N, Cheng V, Dagens A, Hastie C, O'Hara M, Suett J, Dahmash D, Bugaeva P, Rigby I, Munblit D, Harriss E, Burls A, Foote C, Scott J, Carson G, Olliaro P, Sigfrid L, Stavropoulou C. Characterising long COVID: a living systematic review. BMJ Glob Health. 2021 Sep;6(9):e005427. doi: 10.1136/bmjgh-2021-005427.

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Reference Type BACKGROUND
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Yelin D, Moschopoulos CD, Margalit I, Gkrania-Klotsas E, Landi F, Stahl JP, Yahav D. ESCMID rapid guidelines for assessment and management of long COVID. Clin Microbiol Infect. 2022 Jul;28(7):955-972. doi: 10.1016/j.cmi.2022.02.018. Epub 2022 Feb 17.

Reference Type BACKGROUND
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Reference Type BACKGROUND
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Reference Type BACKGROUND
PMID: 34425843 (View on PubMed)

Shechter M, Matetzky S, Feinberg MS, Chouraqui P, Rotstein Z, Hod H. External counterpulsation therapy improves endothelial function in patients with refractory angina pectoris. J Am Coll Cardiol. 2003 Dec 17;42(12):2090-5. doi: 10.1016/j.jacc.2003.05.013.

Reference Type BACKGROUND
PMID: 14680732 (View on PubMed)

Bonetti PO, Barsness GW, Keelan PC, Schnell TI, Pumper GM, Kuvin JT, Schnall RP, Holmes DR, Higano ST, Lerman A. Enhanced external counterpulsation improves endothelial function in patients with symptomatic coronary artery disease. J Am Coll Cardiol. 2003 May 21;41(10):1761-8. doi: 10.1016/s0735-1097(03)00329-2.

Reference Type BACKGROUND
PMID: 12767662 (View on PubMed)

Varanasi S, Sathyamoorthy M, Chamakura S, Shah SA. Management of Long-COVID Postural Orthostatic Tachycardia Syndrome With Enhanced External Counterpulsation. Cureus. 2021 Sep 30;13(9):e18398. doi: 10.7759/cureus.18398. eCollection 2021 Sep.

Reference Type BACKGROUND
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Dayrit JK, Verduzco-Gutierrez M, Teal A, Shah SA. Enhanced External Counterpulsation as a Novel Treatment for Post-acute COVID-19 Sequelae. Cureus. 2021 Apr 7;13(4):e14358. doi: 10.7759/cureus.14358.

Reference Type BACKGROUND
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Yang M, Keller S, Lin JS. Psychometric properties of the PROMIS(R) Fatigue Short Form 7a among adults with myalgic encephalomyelitis/chronic fatigue syndrome. Qual Life Res. 2019 Dec;28(12):3375-3384. doi: 10.1007/s11136-019-02289-4. Epub 2019 Sep 10.

Reference Type BACKGROUND
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Fan X, Lee KS, Frazier SK, Lennie TA, Moser DK. Psychometric testing of the Duke Activity Status Index in patients with heart failure. Eur J Cardiovasc Nurs. 2015 Jun;14(3):214-21. doi: 10.1177/1474515114523354. Epub 2014 Feb 5.

Reference Type BACKGROUND
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Rajala K, Lehto JT, Sutinen E, Kautiainen H, Myllarniemi M, Saarto T. mMRC dyspnoea scale indicates impaired quality of life and increased pain in patients with idiopathic pulmonary fibrosis. ERJ Open Res. 2017 Dec 14;3(4):00084-2017. doi: 10.1183/23120541.00084-2017. eCollection 2017 Oct.

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Reference Type BACKGROUND
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Other Identifiers

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EECP for long COVID-19

Identifier Type: -

Identifier Source: org_study_id