Estimating nocturnal stroke onset times by magnetic resonance imaging in the WAKE-UP trial

2021 ◽  
pp. 174749302110596
Author(s):  
Bastian Cheng ◽  
Hans Pinnschmidt ◽  
Alina Königsberg ◽  
Eckhard Schlemm ◽  
Florent Boutitie ◽  
...  
Keyword(s):  
Linear Regression ◽  
Symptom Onset ◽  
Controlled Trial ◽  
Early Morning ◽  
Stroke Onset ◽  
Lesion Volume ◽  
Night Sleep ◽  
Symptom Recognition ◽  
Fluid Attenuated Inversion Recovery ◽  
Signal Intensities

Background Fluid-attenuated inversion recovery (FLAIR) sequences have gained a role to guide treatment of patients with unknown time of stroke symptom onset. Evolution of signal intensities in FLAIR is associated with time since stroke onset with continuous linear increases. Aims Estimating symptom onset during night-sleep in patients from the WAKE-UP trial based on relative signal intensities FLAIR (FLAIR-rSI) from acute stroke lesions an independent dataset (PRE-FLAIR study). Methods FLAIR-rSI was quantified in stroke lesions in PRE-FLAIR and WAKE-UP. The PRE-FLAIR study was a multicenter observational trial establishing FLAIR as a surrogate parameter for time since stroke onset. WAKE-UP was a randomized controlled trial that revealed a benefit for alteplase in patients selected based on a DWI-FLAIR mismatch. Stroke onset times were recorded in PRE-FLAIR and used to fit a linear regression model with FLAIR-rSI, adjusted for patient age and lesion volume. The model was applied to FLAIR-rSI of stroke lesions to estimate onset times in those patients enrolled in WAKE-UP who had symptom onset during night-sleep. Results FLAIR-rSI was quantified in 399 patients from PRE-FLAIR. Linear regression indicated a significant association of age ( p = 0.001), lesion volume ( p = 0.005) and FLAIR-rSI ( p < 0.001) with time since symptom onset (adjusted R2 = 0.179). In 813 patients from WAKE-UP, distribution of times of last seen well, symptom recognition and MRI examination were recorded. Median times of last seen well were 1 h before midnight (IQR 2.4 h) and symptom recognition 7 h after midnight (IRQ 2.2 h). Based on the FLAIR-rSI profiles, we estimated median stroke onset 6.1 h after midnight (IQR 2.7 h). Conclusion Nocturnal strokes during night-sleep may predominantly occur during the early morning hours. Our results are in line with evidence of characteristic diurnal patterns of cardiovascular events.

scholarly journals Clinical characteristics of unknown symptom onset stroke patients with and without diffusion-weighted imaging and fluid-attenuated inversion recovery mismatch

2017 ◽  
Vol 13 (1) ◽  
pp. 66-73 ◽  
Author(s):  
Götz Thomalla ◽  
Florent Boutitie ◽  
Jochen B Fiebach ◽  
Claus Z Simonsen ◽  
Salvador Pedraza ◽  
...  
Keyword(s):  
Symptom Onset ◽  
Diffusion Weighted Imaging ◽  
Clinical Characteristics ◽  
Controlled Trial ◽  
Inversion Recovery ◽  
Stroke Patients ◽  
Unique Identifier ◽  
Symptom Recognition ◽  
Diffusion Weighted ◽  
Fluid Attenuated Inversion Recovery

Background Diffusion-weighted imaging (DWI) and fluid-attenuated inversion recovery (FLAIR) mismatch was suggested to identify stroke patients with unknown time of symptom onset likely to be within the time window for thrombolysis. Aims We aimed to study clinical characteristics associated with DWI-FLAIR mismatch in patients with unknown onset stroke. Methods We analyzed baseline MRI and clinical data from patients with acute ischemic stroke proven by DWI from WAKE-UP, an investigator-initiated, randomized, placebo-controlled trial of MRI-based thrombolysis in stroke patients with unknown time of symptom onset. Clinical characteristics were compared between patients with and without DWI-FLAIR mismatch. Results Of 699 patients included, 418 (59.8%) presented with DWI-FLAIR mismatch. A shorter delay between last seen well and symptom recognition (p = 0.0063), a shorter delay between symptom recognition and arrival at hospital (p = 0.0025), and history of atrial fibrillation (p = 0.19) were predictors of DWI-FLAIR mismatch in multivariate analysis. All other characteristics were comparable between groups. Conclusions There are only minor differences in measured clinical characteristics between unknown symptom onset stroke patients with and without DWI-FLAIR mismatch. DWI-FLAIR mismatch as an indicator of stroke onset within 4.5 h shows no relevant association with commonly collected clinical characteristics of stroke patients. Clinical Trial Registration URL: http://www.clinicaltrials.gov . Unique identifier: NCT01525290; URL: https://www.clinicaltrialsregister.eu . Unique identifier: 2011-005906-32.

Comparison of stroke volume evolution on diffusion-weighted imaging and fluid-attenuated inversion recovery following endovascular thrombectomy

2016 ◽  
Vol 12 (5) ◽  
pp. 510-518 ◽  
Author(s):  
Christian Federau ◽  
Soren Christensen ◽  
Michael Mlynash ◽  
Jenny Tsai ◽  
Sun Kim ◽  
...  
Keyword(s):  
Symptom Onset ◽  
Diffusion Weighted Imaging ◽  
Infarct Volume ◽  
Inversion Recovery ◽  
Lesion Volume ◽  
Endovascular Thrombectomy ◽  
Post Procedure ◽  
Diffusion Weighted ◽  
Fluid Attenuated Inversion Recovery ◽  
H 26

Background To compare the evolution of the infarct lesion volume on both diffusion-weighted imaging and fluid-attenuated inversion recovery in the first five days after endovascular thrombectomy. Methods We included 109 patients from the CRISP and DEFUSE 2 studies. Stroke lesion volumes obtained on diffusion-weighted imaging and fluid-attenuated inversion recovery images both early post-procedure (median 18 h after symptom onset) and day 5, were compared using median, interquartile range, and correlation plots. Patients were dichotomized based on the time after symptom onset of their post procedure images (≥18 h vs. <18 h), and the degree of reperfusion (on Tmax>6 s; ≥ 90% vs. < 90%). Results Early post-procedure, median infarct lesion volume was 19 ml [(IQR) 7–43] on fluid-attenuated inversion recovery, and 23 ml [11–64] on diffusion-weighted imaging. On day 5, median infarct lesion volume was 52 ml [20–118] on fluid-attenuated inversion recovery, and 37 ml [16–91] on diffusion-weighted imaging. Infarct lesion volume on early post-procedure diffusion-weighted imaging, compared to fluid-attenuated inversion recovery, correlated better with day 5 diffusion-weighted imaging and fluid-attenuated inversion recovery lesions (r = 0.88 and 0.88 vs. 0.78 and 0.77; p < 0.0001). Median lesion growth was significantly smaller on diffusion-weighted imaging when the early post-procedure scan was obtained ≥18 h post stroke onset (5 ml [−1–13]), compared to <18 h (13 ml [2–47]; p = 0.03), but was not significantly different on fluid-attenuated inversion recovery (≥18 h: 26 ml [12–57]; <18 h: 21 ml [5–57]; p = 0.65). In the <90% reperfused group, the median infarct growth was significantly larger for diffusion-weighted imaging and fluid-attenuated inversion recovery (diffusion-weighted imaging: 23 ml [8–57], fluid-attenuated inversion recovery: 41 ml [13–104]) compared to ≥90% (diffusion-weighted imaging: 6 ml [2–24]; p = 0.003, fluid-attenuated inversion recovery: 19 ml [8–46]; p = 0.001). Conclusions Early post-procedure lesion volume on diffusion-weighted imaging is a better estimate of day 5 infarct volume than fluid-attenuated inversion recovery. However, both early post-procedure diffusion-weighted imaging and fluid-attenuated inversion recovery underestimate day 5 diffusion-weighted imaging and fluid-attenuated inversion recovery lesion volumes, especially in patients who do not reperfuse.

Abstract 160: Association Between Time From Stroke Onset and Flair Lesion Intensity is Modified by Status of Collateral Circulation

Stroke ◽  
2016 ◽  
Vol 47 (suppl_1) ◽  
Author(s):  
Anke Wouters ◽  
Patrick Dupont ◽  
Sören Christensen ◽  
Bo Norrving ◽  
Rico Laage ◽  
...  
Keyword(s):  
Symptom Onset ◽  
Signal Intensity ◽  
Collateral Circulation ◽  
Onset Time ◽  
Stroke Onset ◽  
Lesion Volume ◽  
Collateral Flow ◽  
Stroke Patients ◽  
Relative Signal Intensity

Introduction and hypothesis: In acute stroke patients the intensity of a FLAIR lesion in a region of diffusion restriction is associated with time from symptom onset. The DWI/FLAIR mismatch is currently used in trials for treatment of stroke patients with unknown onset time. However the accuracy of the DWI/FLAIR mismatch to predict symptom onset before 4.5h remains moderate. We hypothesized that collateral status, as assessed by the previously described hypoperfusion intensity ratio (HIR) could modify the association between time from stroke onset and FLAIR lesion intensity. Methods: From the ‘Ax200 for ischemic stroke trial’ 141 patients were included. Quantitative FLAIR maps were calculated in a voxel-based manner. For each voxel the relative signal intensity (rSI) was determined by the ratio of the signal intensity in that voxel and the median of the signal intensity in a sphere with radius 15mm positioned in the homologue voxel in the other hemisphere. Lesion volumes based on diffusion-weighted imaging and perfusion-weighted imaging were determined using RAPID software. The HIR was defined as the proportion of a Tmax >6 s lesion volume with a Tmax >10 s delay. A previously defined HIR-threshold of ≤ 0.4 dichotomized good versus poor collaterals. We studied the interaction between collateral circulation and the association between time from symptom onset and FLAIR intensity. Results: Time from symptom onset was associated with the mean FLAIR intensity in the region of non-reperfused core (b=1.05; 95%CI: 1.01-1.1). We identified an interaction between this association and collateral status (p=0.036). ROC analysis of FLAIR intensity to predict stroke onset before 4.5h showed an AUC of 0.66 (95% CI: 0. 49-0.83) for patients with good collaterals and 0.80 (95%CI: 0.71-0.90) for patients with poor collaterals. Conclusions: Our findings suggest that the progression of FLAIR intensity with time varies depending on the quality of the collateral flow. Accordingly collateral circulation influences the accuracy of FLAIR lesion intensity to predict stroke onset before 4.5h. This could be of particular importance for clinical trials enrolling patients based on the DWI/FLAIR mismatch.

scholarly journals Quantitative Measurements of Relative Fluid-Attenuated Inversion Recovery (FLAIR) Signal Intensities in Acute Stroke for the Prediction of Time from Symptom Onset

2012 ◽  
Vol 33 (1) ◽  
pp. 76-84 ◽  
Author(s):  
Bastian Cheng ◽  
Mathias Brinkmann ◽  
Nils D Forkert ◽  
Andras Treszl ◽  
Martin Ebinger ◽  
...  
Keyword(s):  
Acute Stroke ◽  
Symptom Onset ◽  
Visual Analysis ◽  
Onset Time ◽  
Inversion Recovery ◽  
Classification And Regression Tree ◽  
Lesion Volume ◽  
Ischemic Lesion ◽  
Quantitative Measurements ◽  
Fluid Attenuated Inversion Recovery

In acute stroke magnetic resonance imaging, a ‘mismatch’ between visibility of an ischemic lesion on diffusion-weighted imaging (DWI) and missing corresponding parenchymal hyperintensities on fluid-attenuated inversion recovery (FLAIR) data sets was shown to identify patients with time from symptom onset ≤4.5 hours with high specificity. However, moderate sensitivity and suboptimal interpreter agreement are limitations of a visual rating of FLAIR lesion visibility. We tested refined image analysis methods in patients included in the previously published PREFLAIR study using refined visual analysis and quantitative measurements of relative FLAIR signal intensity (rSI) from a three-dimensional, segmented stroke lesion volume. A total of 399 patients were included. The rSI of FLAIR lesions showed a moderate correlation with time from symptom onset ( r = 0.382, P < 0.001). A FLAIR rSI threshold of <1.0721 predicted symptom onset ≤4.5 hours with slightly increased specificity (0.85 versus 0.78) but also slightly decreased sensitivity (0.47 versus 0.58) as compared with visual analysis. Refined visual analysis differentiating between ‘subtle’ and ‘obvious’ FLAIR hyperintensities and classification and regression tree algorithms combining information from visual and quantitative analysis also did not improve diagnostic accuracy. Our results raise doubts whether the prediction of stroke onset time by visual image judgment can be improved by quantitative rSI measurements.

scholarly journals Does Symptom Recognition Improve Self-Care in Patients with Heart Failure? A Pilot Study Randomised Controlled Trial

2021 ◽  
Vol 11 (2) ◽  
pp. 418-429
Author(s):  
Joana Pereira Sousa ◽  
Hugo Neves ◽  
Miguel Pais-Vieira
Keyword(s):  
Quality Of Life ◽  
Heart Failure ◽  
Care Management ◽  
Controlled Trial ◽  
Self Care ◽  
Fluid Restriction ◽  
Symptom Recognition ◽  
Patients With Heart Failure ◽  
Randomised Controlled

Patients with heart failure have difficulty in self-care management, as daily monitoring and recognition of symptoms do not readily trigger an action to avoid hospital admissions. The purpose of this study was to understand the impact of a nurse-led complex intervention on symptom recognition and fluid restriction. A latent growth model was designed to estimate the longitudinal effect of a nursing-led complex intervention on self-care management and quality-of-life changes in patients with heart failure and assessed by a pilot study performed on sixty-three patients (33 control, 30 intervention). Patients in the control group had a higher risk of hospitalisation (IRR 11.36; p < 0.001) and emergency admission (IRR 4.24; p < 0.001) at three-months follow-up. Analysis of the time scores demonstrated that the intervention group had a clear improvement in self-care behaviours (βSlope. Assignment_group = −0.881; p < 0.001) and in the quality of life (βSlope. Assignment_group = 1.739; p < 0.001). This study supports that a nurse-led programme on symptom recognition and fluid restriction can positively impact self-care behaviours and quality of life in patients with heart failure. This randomised controlled trial was retrospectively registered (NCT04892004).

scholarly journals A multicenter randomized controlled trial of endovascular therapy following imaging evaluation for ischemic stroke (DEFUSE 3)

2017 ◽  
Vol 12 (8) ◽  
pp. 896-905 ◽  
Author(s):  
Gregory W Albers ◽  
Maarten G Lansberg ◽  
Stephanie Kemp ◽  
Jenny P Tsai ◽  
Phil Lavori ◽  
...  
Keyword(s):  
Computed Tomography ◽  
Ischemic Stroke ◽  
Magnetic Resonance ◽  
Primary Endpoint ◽  
Endovascular Therapy ◽  
Symptom Onset ◽  
Medical Management ◽  
Controlled Trial ◽  
Modified Rankin Scale ◽  
Computed Tomography Perfusion

Rationale Early reperfusion in patients experiencing acute ischemic stroke is effective in patients with large vessel occlusion. No randomized data are available regarding the safety and efficacy of endovascular therapy beyond 6 h from symptom onset. Aim The aim of the study is to demonstrate that, among patients with large vessel anterior circulation occlusion who have a favorable imaging profile on computed tomography perfusion or magnetic resonance imaging, endovascular therapy with a Food and Drug Administration 510 K-cleared mechanical thrombectomy device reduces the degree of disability three months post stroke. Design The study is a prospective, randomized, multicenter, phase III, adaptive, blinded endpoint, controlled trial. A maximum of 476 patients will be randomized and treated between 6 and 16 h of symptom onset. Procedures Patients undergo imaging with computed tomography perfusion or magnetic resonance diffusion/perfusion, and automated software (RAPID) determines if the Target Mismatch Profile is present. Patients who meet both clinical and imaging selection criteria are randomized 1:1 to endovascular therapy plus medical management or medical management alone. The individual endovascular therapist chooses the specific device (or devices) employed. Study outcomes The primary endpoint is the distribution of scores on the modified Rankin Scale at day 90. The secondary endpoint is the proportion of patients with modified Rankin Scale 0–2 at day 90 (indicating functional independence). Analysis Statistical analysis for the primary endpoint will be conducted using a normal approximation of the Wilcoxon–Mann–Whitney test (the generalized likelihood ratio test).

Abstract 3851: Temporal Distribution of Stroke Volumes and Clinical-Diffusion Mismatch in Patients with Proximal Arterial Occlusions

Stroke ◽  
2012 ◽  
Vol 43 (suppl_1) ◽  
Author(s):  
Raul G Nogueira ◽  
David S Liebeskind ◽  
Leticia M Souza ◽  
Qing Hao ◽  
Karen Furie ◽  
...  
Keyword(s):  
Linear Regression ◽  
Infarct Volume ◽  
Linear Regression Analysis ◽  
Significant Proportion ◽  
Arterial Occlusion ◽  
Reperfusion Therapy ◽  
Poor Correlation ◽  
Lesion Volume ◽  
Collateral Flow ◽  
Over Time

Background and Purpose: Previous studies have demonstrated that the benefit of reperfusion therapy declines over time. The Clinical-Diffusion Mismatch (CDM) model has been suggested as surrogate for salvable tissue in acute ischemic stroke (AIS) patients. We sought to describe the temporal behavior profile of infarct volumes and CDM in patients suffering AIS due to proximal arterial occlusion (PAO). Methods: We performed a retrospective analysis of consecutive AIS patients admitted to two large academic institutions fulfilling the following criteria: (1) Baseline NIHSS ≥8; (2) PAO defined as MCA-M1, intracranial ICA, or tandem cervical + ICA/MCA-M1 occlusion on admission CTA/MRA; and (3) MRI-DWI performed ≤8 hours from time of stroke onset/last seen well (TSO). CDM was defined as baseline NIHSS ≥8 and DWI volume ≤25cc (as proposed by Davalos et al). Linear regression analysis was performed to define the changes on DWI lesion volume on presentation over time. The observed TSO to MRI were broken down into quartiles to look for any differences in the distribution of the baseline variables over time. Results: A total of 132 consecutive patients were identified (mean age, 66±16.8 years; 57% females; mean baseline NIHSS 17.5±5.3; occlusion site: MCA-M1, 64%; intracranial-ICA, 29%; tandem, 5%, mean TSO to DWI, 269.5±105.48 minutes). The mean DWI stroke volume on presentation was 46.7±54.8 cc (range, 0.19-436.1) and 63 (46.7%) patients had CDM. There was no significant changes in age, gender, baseline NIHSS, or occlusion site amongst the different time quartiles. Median infarct volume (cc) increased (quartile #1=8.5; #2=30.1; #3=38.5; #4=29.4) and the chances of having a CDM decreased (p<0.0001) across the different time quartiles. However, there was an overall poor correlation between DWI lesion volume on presentation and TSO to MRI (R-square=0.031, Figure ) and a significant proportion of the patients still had a CDM at later time epochs (#1=91.1%[20/22]; #2=47.8%[11/23]; #3=34.4%[21/61]; #4=42.3%[11/26]). Conclusions: Although infarct volume increases and the amount of penumbral tissue decreases over time, many patients with PAO will still have salvable penumbra at the later time epochs. This reflects individual differences in anatomic and physiological characteristics including the strength of collateral flow and highlights that selected patients may benefit from reperfusion therapy even at the later time windows. Figure : Relationship between Baseline DWI Volume (cc) and Time (minutes). Line is best fitted linear regression model.

scholarly journals Clinical and Radiological Correlates of Reduced CBF Measured Using MRI

Stroke ◽  
2001 ◽  
Vol 32 (suppl_1) ◽  
pp. 317-318
Author(s):  
Vincent N Thijs ◽  
Tobias Neumann-Haefelin ◽  
Michael E Moseley ◽  
Michael P Marks ◽  
Gregory W Albers
Keyword(s):  
Symptom Onset ◽  
Cerebral Blood Volume ◽  
Arterial Input Function ◽  
Mean Transit Time ◽  
Input Function ◽  
Lesion Volume ◽  
Time Curve ◽  
Measured Concentration ◽  
Ischemic Lesion ◽  
Adc Values

11 Background and purpose Methods for determining CBF using IV bolus tracking MRI have recently become available. Reduced apparent diffusion coefficient (ADC) values of brain tissue are associated with reductions in regional cerebral blood flow (rCBF). We studied the clinical and radiological features of patients with severe reductions of rCBF on MRI and analysed the relationship between reduced rCBF and ADC. Methods We studied patients with non-lacunar acute ischemic stroke in whom PWI and DWI MRI were performed within 7 hours after symptom onset. A PWI>DWI mismatch of >20% was required. Maps of rCBF, cerebral blood volume (rCBV) and mean transit time (rMTT) were generated after deconvoluting the measured concentration-time curve with the arterial input function using singular value decomposition. The ischemic lesion was outlined on the MTT map and the region of interest (ROI) transferred to the rCBF and rCBV map. ADC-maps were calculated. ADC lesions were defined as regions with ADC values ≤ 550 μm m2/sec. We compared the characteristics of patients with ischemic lesions that had a relative CBF of <50% to the contralateral hemisphere to patients with lesions that had relative CBF of >50%. Characteristics analysed included age, time to MRI, baseline NIHSS, mean ADC, DWI lesion volume, PWI lesion volume and absolute mismatch volume. Results Fifteen patients with an initial PWI>DWI mismatch of >20% were included. Ten had lesions with rCBF of >50% (median 60%) and five patients had rCBF of <50% (median 27.7%). Patients with rCBF <50% had lower ADC values (median 431 μmm2/sec versus 506 μ mm2/sec, p=0.028), larger DWI volumes (median 75.6 cm 3 versus 8.6 cm 3 , p=0.001) and larger PWI lesions as defined by the MTT volume (median 193 cm 3 versus 69 cm 3 , p=0.028) and more severe baseline NIHSS scores (median 18 versus 9, p=0.019). The rMTT and rCBV of the lesions were similar in both groups, as were the age, the absolute mismatch volume and the time from symptom onset to MRI. Conclusion These data indicate that ischemic lesions with severe CBF reductions, measured with new MRI techniques, are associated with a lower mean ADC, larger DWI and PWI lesion volumes and a higher NIHSS score.

Abstract WP221: Very Brief Intervention Improves Stroke Response in a Randomized Trial: Stroke Ready Very Brief Intervention

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Lesli E Skolarus ◽  
Maria Cielito Robles ◽  
Springer Mellanie ◽  
Chun Chieh Lin ◽  
Casey Corches ◽  
...  
Keyword(s):  
Brief Intervention ◽  
Action Plan ◽  
Controlled Trial ◽  
Intervention Group ◽  
Secondary Outcome ◽  
Average Score ◽  
Control Group ◽  
Symptom Recognition ◽  
Stroke Symptom ◽  
One To One

Introduction: Stroke pre-hospital delay has not improved over time. Hypothesis: Stroke Ready, a very brief (5 minute), theory based, peer-led, stroke preparedness intervention, will increase stroke response compared with a control intervention. Methods: We performed a randomized, single-blind controlled trial among adults in Flint, MI. The stroke preparedness intervention group received a Stroke Ready pamphlet and action plan, while the control group received stroke prevention materials - both delivered during a one-to-one interaction with a trained peer educator. Research staff, blinded to group intervention assignment, assessed baseline and immediate post-intervention outcomes. Primary outcome was change in stroke response (behavioral intent to call 911) using a community-modified stroke action test (range 0-12). Secondary outcome was change in stroke symptom recognition (range 0-8). We conducted descriptive analyses and used a linear regression model to evaluate the effect of the intervention on stroke response after adjustment for pre-intervention intent, age, education, race, marital status, history of stroke, stroke in someone they know and psychological constructs. Results: We enrolled 129 participants (74 intervention; 55 control). Mean age was 60 years (SD 14); 61% were women, 89% were African American and 19% were not high school graduates. Intervention participants had greater improvement in stroke response than control participants (figure 1), which remained after full adjustment (improvement in average score for stroke response was 1.7 higher in intervention participants than control participants, 95% CI 0.9-2.5, p<0.0001). There was no difference in stroke symptom recognition (figure 1). Conclusion: The Stroke Ready very brief intervention increased stroke response. This new approach using a very brief, one-to-one interaction with trained peer educators is a promising, scalable, intervention to increase stroke response.

scholarly journals Hydroxychloroquine for Early Treatment of Adults With Mild Coronavirus Disease 2019: A Randomized, Controlled Trial

2020 ◽  
Author(s):  
Oriol Mitjà ◽  
Marc Corbacho-Monné ◽  
Maria Ubals ◽  
Cristian Tebé ◽  
Judith Peñafiel ◽  
...  
Keyword(s):  
Randomized Controlled Trial ◽  
Viral Load ◽  
Adverse Events ◽  
Usual Care ◽  
Symptom Onset ◽  
Early Treatment ◽  
Complete Resolution ◽  
Controlled Trial ◽  
Randomized Controlled ◽  
The Mean

Abstract Background No effective treatments for coronavirus disease 2019 (COVID-19) exist. We aimed to determine whether early treatment with hydroxychloroquine (HCQ) would be efficacious for outpatients with COVID-19. Methods Multicenter open-label, randomized, controlled trial conducted in Catalonia, Spain, between 17 March and 26 May 2020. Patients recently diagnosed with &lt;5-day of symptom onset were assigned to receive HCQ (800 mg on day 1 followed by 400 mg once daily for 6 days) or usual care. Outcomes were reduction of viral load in nasopharyngeal swabs up to 7 days after treatment start, disease progression up to 28 days, and time to complete resolution of symptoms. Adverse events were assessed up to 28 days. Results A total of 293 patients were eligible for intention-to-treat analysis: 157 in the control arm and 136 in the intervention arm. The mean age was 41.6 years (SD, 12.6), mean viral load at baseline was 7.90 log10 copies/mL (SD, 1.82), and median time from symptom onset to randomization was 3 days. No differences were found in the mean reduction of viral load at day 3 (−1.41 vs −1.41 log10 copies/mL in the control and intervention arm, respectively) or at day 7 (−3.37 vs −3.44). Treatment did not reduce risk of hospitalization (7.1% control vs 5.9% intervention) nor shorten the time to complete resolution of symptoms (12 days, control vs 10 days, intervention). No relevant adverse events were reported. Conclusions In patients with mild COVID-19, no benefit was observed with HCQ beyond the usual care.

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