Progesterone vs placebo therapy for women with epilepsy: A randomized clinical trial.
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SUBMITTER: Herzog AG
PROVIDER: S-EPMC3369508 | biostudies-literature | 2012 Jun
REPOSITORIES: biostudies-literature
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Progesterone vs placebo therapy for women with epilepsy: A randomized clinical trial.
Herzog A G AG Fowler K M KM Smithson S D SD Kalayjian L A LA Heck C N CN Sperling M R MR Liporace J D JD Harden C L CL Dworetzky B A BA Pennell P B PB Massaro J M JM
Neurology 20120530 24
<h4>Objective</h4>To assess progesterone treatment of intractable seizures in women with partial epilepsy.<h4>Methods</h4>This randomized, double-blind, placebo-controlled, phase III, multicenter, clinical trial compared the efficacy and safety of adjunctive cyclic natural progesterone therapy vs placebo treatment of intractable seizures in 294 subjects randomized 2:1 to progesterone or placebo, stratified by catamenial and noncatamenial status. It compared treatments on proportions of ≥50% resp ...[more]
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Project description:Study questionIn women with threatened miscarriage, does progesterone supplementation until the completion of the first trimester of pregnancy increase the probability of live birth?Summary answerIn women with threatened miscarriage, 400 mg vaginal progesterone nightly, from onset of bleeding until 12 weeks, did not increase live birth rates.What is known alreadyLimited evidence has indicated that vaginal micronized progesterone may make little or no difference to the live birth rate when compared with placebo in women with threatened miscarriage. Subgroup analysis of one recent randomized trial reported that in women with bleeding and at least one previous miscarriage, progesterone might be of benefit.Study design, size, durationWe performed a randomized, double-blinded, placebo-controlled trial between February 2012 and April 2019. Eligible pregnant women under 10 weeks gestation, experiencing a threatened miscarriage as apparent from vaginal bleeding were randomized into two groups in a 1:1 ratio: the intervention group received 400 mg progesterone as vaginal pessaries, the control group received placebo vaginal pessaries, both until 12 weeks gestation. The primary endpoint was live birth. We planned to randomize 386 women (193 per group). The study was stopped at a planned interim analysis for futility after randomization of 278 women.Participants/materials, setting, methodsThis trial was conducted at the Mater Mothers' Hospital, a tertiary centre for maternity care in South Brisbane, Queensland, Australia. We randomized 139 women to the intervention group and 139 women to the placebo group. Primary outcome data were available for 136 women in the intervention group and 133 women in the placebo group.Main results and the role of chanceThe live birth rates were 82.4% (112/136) and 84.2% (112/133) in the intervention group and placebo group, respectively (risk ratio (RR) 0.98, 95% CI 0.88 to 1.09; risk difference -0.02, 95% CI -0.11 to 0.07; P = 0.683). Among women with at least one previous miscarriage, live birth rates were 80.6% (54/67) and 84.4% (65/77) (RR 0.95, 95% CI 0.82-1.11; P = 0.550). No significant effect was seen from progesterone in women with two (RR 1.28, 95% CI 0.96-1.72; P = 0.096) or more (RR 0.79, 95% CI 0.53-1.19; P = 0.267) previous miscarriages. Preterm birth rates were 12.9% and 9.3%, respectively (RR 1.38; 95% CI 0.69 to 2.78; P = 0.361). Median birth weight was 3310 vs 3300 g (P = 0.992). There were also no other significant differences in obstetric and perinatal outcomes.Limitations, reasons for cautionOur study was single centre and did not reach the planned sample size because it was stopped prematurely at an interim analysis.Wider implications of the findingsWe did not find evidence supporting the treatment effect of vaginal progesterone in women with threatened miscarriage. Progesterone in this setting should not be routinely used for threatened miscarriage. The treatment effect in women with threatened miscarriage after previous miscarriages warrants further research.Study funding/competing interest(s)Mothers' and babies Golden Casket Clinical Fellowship (L.A.M.). Progesterone and placebo pessaries were provided by Perrigo Australia.B.W.J.M. reports grants from NHMRC, personal fees from ObsEva, personal fees from Merck KGaA, personal fees from Guerbet, personal fees from iGenomix, outside the submitted work.Trial registration numberACTRN12611000405910.Trial registration date19 April 2011.Date of first patient’s enrolment06 February 2012.
| S-EPMC10069850 | biostudies-literature
Project description:BACKGROUND AND AIMS:In some clinical studies men and women have been found to differ in their ability to quit smoking, perhaps as a result of progesterone. The primary aim of this study was to provide a preliminary test of whether progesterone (PRO), compared with placebo (PBO), was more effective for smoking cessation in men and women. DESIGN:Pilot double-blind, placebo-controlled randomized clinical trial. SETTING:Minneapolis/St Paul metro area, Minnesota, USA. PARTICIPANTS:A total of 216 participants were randomized, including 113 men (18-60 years; PRO = 56, PBO = 57) and 103 women (18-50 years, pre-menopausal with self-reported regular menstrual cycles; PRO = 51, PBO = 52). INTERVENTION:Participants were randomized (1 : 1 within sex group) to either PRO (200 mg twice daily) or PBO. Participants were assigned a quit date approximately 7 days after starting medication (luteal phase for women) and were followed for 12 weeks to assess relapse. MEASUREMENTS:The primary outcome was self-reported 7-day point prevalence abstinence (PPA) at week 4. Secondary outcomes included 7-day PPA at weeks 8 and 12, prolonged abstinence, continuous abstinence, urine cotinine < 50 ng/ml, expired carbon monoxide ? 5 parts per million (p.p.m.) and days to relapse. FINDINGS:There was a significant difference in 7-day PPA at week 4 among women [PRO: 18 (35.3%) versus PBO: 9 (17.3%), odds ratio (OR) = 2.61, 95% confidence interval (CI) = 1.04, 6.54, P = 0.041], but not among men [PRO: 13 (23.2%) versus PBO: 12 (21.1%), 1.13 (0.47, 2.76), P = 0.782]. There was some evidence that PRO delayed relapse in women (days to relapse; PRO: 20.5 ± 29.6 versus PBO: 14.3 ± 26.8, P = 0.03) but not in men (PRO: 13.4 ± 25.9 versus PBO: 13.3 ± 23.8, P = 0.69). CONCLUSIONS:Oral micronized progesterone may aid smoking cessation in women.
| S-EPMC6732045 | biostudies-literature
Project description:BackgroundProgesterone is effective treatment for hot flushes/night sweats. The cardiovascular effects of progesterone therapy are unknown but evidence suggests that premenopausal normal estradiol with also normal progesterone levels may provide later cardiovascular protection. We compared the effects of progesterone to placebo on endothelial function, weight, blood pressure, metabolism, lipids, inflammation and coagulation.Methods and resultsWe conducted a randomized, double-blind, 3-month placebo-controlled trial of progesterone (300 mg daily) among 133 healthy postmenopausal women in Vancouver, Canada from 2003-2009. Endothelial function by venous occlusion plethysmography was a planned primary outcome. Enrolled women were 1-11 y since last menstruation, not using hormones (for >6 months), non-smoking, without diabetes, hypertension, heart disease or their medications. Randomized (1∶1) women (55 ± 4 years, body mass index 25 ± 3) initially had normal blood pressure, fasting lipid, glucose and electrocardiogram results. Endothelial function (% forearm blood flow above saline) was not changed with progesterone (487 ± 189%, n = 18) compared with placebo (408 ± 278%, n = 16) (95% CI diff [-74 to 232], P = 0.30). Progesterone (n = 65) and placebo (n = 47) groups had similar changes in systolic and diastolic blood pressure, resting heart rate, weight, body mass index, waist circumference, total cholesterol, low-density lipoprotein cholesterol and triglyceride levels. High-density lipoprotein was lower (-0.14 mmol/L, P = 0.001) on progesterone compared with placebo. Fasting glucose, hs-C-reactive protein, albumin and D-dimer changes were all comparable to placebo. Framingham General Cardiovascular Risk Profile scores were initially low and remained low with progesterone therapy and not statistically different from placebo.ConclusionsResults indicate that progesterone has short-term cardiovascular safety. Endothelial function, weight, blood pressure, waist circumference, inflammation and coagulation were unchanged as were lipids except for HDL-C. The statistically significant decrease in HDL-C levels was not clinically important (based on lack of Cardiovascular Risk Profile change).Trial registrationClinicalTrials.gov NCT00152438.
| S-EPMC3897380 | biostudies-literature
Project description:Importance:External vibration therapy (EVT) has been widely used in chronic pain conditions, musculoskeletal rehabilitation, and athletic training. Vibration therapy has been suggested to enhance vocal performance and has been popularized in social media. However, there is no evidence to support its effect on vocal function. Objective:To evaluate the immediate effects of EVT in trained singers using acoustic and self-assessment parameters. Design, Setting, and Participants:Prospective, randomized, placebo-controlled interventional study at St Michael's Hospital Voice Clinic, affiliated with the University of Toronto. Data collection and analysis were performed by investigators who were blinded to the group assignment of the participants. Study participants were randomized to EVT or a placebo (control) group. The study dates were September 2015 to December 2016. Interventions:Participants attended the voice laboratory at St Michael's Hospital, where a standardized data collection protocol was performed, including acoustic parameters, voice range profile, and soft voice tasks, followed by subjective rating of vocal effort or discomfort. The EVT group underwent EVT to 5 neck sites bilaterally. The placebo group underwent the same protocol with a modified device. After the intervention, the participants repeated the standardized data collection. Main Outcomes and Measures:The primary outcome in this study was acoustic analysis (jitter, shimmer, and pitch range) compared before and after treatment. In addition, secondary outcomes included perceived effort or discomfort evaluated by participants after 4 voice tasks proposed to investigate more subtle voice properties. Within and between groups, data sets were statistically analyzed for potential treatment effect. Results:Among 27 participants (age range, 18-50 years; all female), 14 were randomized to the intervention group and 13 to the placebo group. Comparison of the treatment effect on the vowel token acoustic parameters evaluated showed that, after EVT, participants had a more cohesive change with a restricted 95% CI compared with placebo. The mean change in fundamental frequency after intervention was 5.00 Hz in both groups but the 95% CI was much wider after placebo (-30.30 to 19.20) than after EVT (-18.10 to 7.50). After EVT, the effect size was notable in the vowel (0.83) and SVT3 (0.79) task. Conclusions and Relevance:In this study, EVT demonstrated a more predictable change in acoustic metrics compared with the placebo treatment. Effort ratings for 6 voice tasks evaluated in this study were not found to be different after EVT compared with the placebo treatment. Trial Registration:clinicaltrials.gov Identifier: NCT02083341.
| S-EPMC5885875 | biostudies-literature
Project description:ImportanceSevere early onset fetal growth restriction caused by placental dysfunction leads to high rates of perinatal mortality and neonatal morbidity. The phosphodiesterase 5 inhibitor, sildenafil, inhibits cyclic guanosine monophosphate hydrolysis, thereby activating the effects of nitric oxide, and might improve uteroplacental function and subsequent perinatal outcomes.ObjectiveTo determine whether sildenafil reduces perinatal mortality or major morbidity.Design, setting, and participantsThis placebo-controlled randomized clinical trial was conducted at 10 tertiary referral centers and 1 general hospital in the Netherlands from January 20, 2015, to July 16, 2018. Participants included pregnant women between 20 and 30 weeks of gestation with severe fetal growth restriction, defined as fetal abdominal circumference below the third percentile or estimated fetal weight below the fifth percentile combined with Dopplers measurements outside reference ranges or a maternal hypertensive disorder. The trial was stopped early owing to safety concerns on July 19, 2018, whereas benefit on the primary outcome was unlikely. Data were analyzed from January 20, 2015, to January 18, 2019. The prespecified primary analysis was an intention-to-treat analysis including all randomized participants.InterventionsParticipants were randomized to sildenafil, 25 mg, 3 times a day vs placebo.Main outcomes and measuresThe primary outcome was a composite of perinatal mortality or major neonatal morbidity until hospital discharge.ResultsOut of 360 planned participants, a total of 216 pregnant women were included, with 108 women randomized to sildenafil (median gestational age at randomization, 24 weeks 5 days [interquartile range, 23 weeks 3 days to 25 weeks 5 days]; mean [SD] estimated fetal weight, 458 [160] g) and 108 women randomized to placebo (median gestational age, 25 weeks 0 days [interquartile range, 22 weeks 5 days to 26 weeks 3 days]; mean [SD] estimated fetal weight, 464 [186] g). In July 2018, the trial was halted owing to concerns that sildenafil may cause neonatal pulmonary hypertension, whereas benefit on the primary outcome was unlikely. The primary outcome, perinatal mortality or major neonatal morbidity, occurred in the offspring of 65 participants (60.2%) allocated to sildenafil vs 58 participants (54.2%) allocated to placebo (relative risk, 1.11; 95% CI, 0.88-1.40; P = .38). Pulmonary hypertension, a predefined outcome important for monitoring safety, occurred in 16 neonates (18.8%) in the sildenafil group vs 4 neonates (5.1%) in the placebo group (relative risk, 3.67; 95% CI, 1.28-10.51; P = .008).Conclusions and relevanceThese findings suggest that antenatal maternal sildenafil administration for severe early onset fetal growth restriction did not reduce the risk of perinatal mortality or major neonatal morbidity. The results suggest that sildenafil may increase the risk of neonatal pulmonary hypertension.Trial registrationClinicalTrials.gov Identifier: NCT02277132.
| S-EPMC7301225 | biostudies-literature
Project description:ImportancePostpartum depression (PPD) is one of the most common medical complications during and after pregnancy, negatively affecting both mother and child.ObjectiveTo demonstrate the efficacy and safety of zuranolone, a neuroactive steroid γ-aminobutyric acid receptor-positive allosteric modulator, in PPD.Design, setting, and participantsThis phase 3, double-blind, randomized, outpatient, placebo-controlled clinical trial was conducted between January 2017 and December 2018 in 27 enrolling US sites. Participant were women aged 18 to 45 years, 6 months or fewer post partum, with PPD (major depressive episode beginning third trimester or ≤4 weeks postdelivery), and baseline 17-item Hamilton Rating Scale for Depression (HAMD-17) score of 26 or higher. Analysis was intention to treat and began December 2018 and ended March 2019.InterventionsRandomization 1:1 to placebo:zuranolone, 30 mg, administered orally each evening for 2 weeks.Main outcomes and measuresPrimary end point was change from baseline in HAMD-17 score for zuranolone vs placebo at day 15. Secondary end points included changes from baseline in HAMD-17 total score at other time points, HAMD-17 response (≥50% score reduction) and remission (score ≤7) rates, Montgomery-Åsberg Depression Rating Scale score, and Hamilton Rating Scale for Anxiety score. Safety was assessed by adverse events and clinical assessments.ResultsOf 153 randomized patients, the efficacy set comprised 150 patients (mean [SD] age, 28.3 [5.4] years), and 148 (98.7%) completed treatment. A total of 76 patients were randomized to placebo, and 77 were randomized to zuranolone, 30 mg. Zuranolone demonstrated significant day 15 HAMD-17 score improvements from baseline vs placebo (-17.8 vs -13.6; difference, -4.2; 95% CI, -6.9 to -1.5; P = .003). Sustained differences in HAMD-17 scores favoring zuranolone were observed from day 3 (difference, -2.7; 95% CI, -5.1 to -0.3; P = .03) through day 45 (difference, -4.1; 95% CI, -6.7 to -1.4; P = .003). Sustained differences at day 15 favoring zuranolone were observed in HAMD-17 response (odds ratio, 2.63; 95% CI, 1.34-5.16; P = .005), HAMD-17 score remission (odds ratio, 2.53; 95% CI, 1.24-5.17; P = .01), change from baseline for Montgomery-Åsberg Depression Rating Scale score (difference, -4.6; 95% CI, -8.3 to -0.8; P = .02), and Hamilton Rating Scale for Anxiety score (difference, -3.9; 95% CI, -6.7 to -1.1; P = .006). One patient per group experienced a serious adverse event (confusional state in the zuranolone group and pancreatitis in the placebo group). One patient in the zuranolone group discontinued because of an adverse event vs none for placebo.Conclusions and relevanceIn this randomized clinical trial, zuranolone improved the core symptoms of depression as measured by HAMD-17 scores in women with PPD and was generally well tolerated, supporting further development of zuranolone in the treatment of PPD.Trial registrationClinicalTrials.gov Identifier: NCT02978326.
| S-EPMC8246337 | biostudies-literature
Project description:ImportanceCorticosteroid injections and exercise therapy are commonly used to treat chronic midportion Achilles tendinopathy, but the evidence for this combination is limited.ObjectiveTo investigate the effect of corticosteroid injection and exercise therapy compared with placebo injection and exercise therapy for patients with Achilles tendinopathy.Design, setting, and participantsThis was a participant-blinded, physician-blinded, and assessor-blinded randomized clinical trial of patients with Achilles tendinopathy verified by ultrasonography. Assessment of pain and function were conducted at baseline and at 1, 2, 3, 6, 12, and 24 months. Patients were recruited from a university medical clinic and a private rheumatology clinic in Denmark between April 2016 and September 2018. Data analysis was performed from June to September 2021.InterventionsCorticosteroid injection and placebo injection were performed with ultrasonography guidance. Exercise therapy was based on previous trials and consisted of 3 exercises done every second day.Main outcomes and measuresThe primary outcome was the Victorian Institute of Sports Assessment-Achilles (VISA-A) score (range, 1-100, with 100 representing no symptoms) at 6 months. Secondary outcomes included pain measured using a 100-mm Visual Analog Scale for morning pain and pain during exercise (with higher scores indicating worse pain), global assessment (Likert scale), and tendon thickness.ResultsA total of 100 patients were included, with 52 randomized to placebo (mean age, 46 years [95% CI, 44-48 years]; 32 men [62%]) and 48 randomized to corticosteroid injection (mean age, 47 years [95% CI, 45-49 years]; 28 men [58%]). Patients in the 2 groups had similar height (mean [SD], 177 [8] cm), weight (mean [SD], 79 [12] kg), and VISA-A score (mean [SD], 46 [18]) at baseline. The group receiving exercise therapy combined with corticosteroid injections had a 17.7-point (95% CI, 8.4-27.0 points; P < .001) larger improvement in VISA-A score compared with patients receiving exercise therapy combined with placebo injections at 6 months. No severe adverse events were observed in either group, and there was no deterioration in the long term (2-year follow-up).Conclusions and relevanceCorticosteroid injections combined with exercise therapy were associated with better outcomes in the treatment of Achilles tendinopathy compared with placebo injections and exercise therapy. A combination of exercise therapy and corticosteroid injection should be considered in the management of long-standing Achilles tendinopathy.Trial registrationClinicalTrials.gov Identifier: NCT02580630.
| S-EPMC9274322 | biostudies-literature
Project description:ImportanceChronic back pain (CBP) is a leading cause of disability, and treatment is often ineffective. Approximately 85% of cases are primary CBP, for which peripheral etiology cannot be identified, and maintenance factors include fear, avoidance, and beliefs that pain indicates injury.ObjectiveTo test whether a psychological treatment (pain reprocessing therapy [PRT]) aiming to shift patients' beliefs about the causes and threat value of pain provides substantial and durable pain relief from primary CBP and to investigate treatment mechanisms.Design, setting, and participantsThis randomized clinical trial with longitudinal functional magnetic resonance imaging (fMRI) and 1-year follow-up assessment was conducted in a university research setting from November 2017 to August 2018, with 1-year follow-up completed by November 2019. Clinical and fMRI data were analyzed from January 2019 to August 2020. The study compared PRT with an open-label placebo treatment and with usual care in a community sample.InterventionsParticipants randomized to PRT participated in 1 telehealth session with a physician and 8 psychological treatment sessions over 4 weeks. Treatment aimed to help patients reconceptualize their pain as due to nondangerous brain activity rather than peripheral tissue injury, using a combination of cognitive, somatic, and exposure-based techniques. Participants randomized to placebo received an open-label subcutaneous saline injection in the back; participants randomized to usual care continued their routine, ongoing care.Main outcomes and measuresOne-week mean back pain intensity score (0 to 10) at posttreatment, pain beliefs, and fMRI measures of evoked pain and resting connectivity.ResultsAt baseline, 151 adults (54% female; mean [SD] age, 41.1 [15.6] years) reported mean (SD) pain of low to moderate severity (mean [SD] pain intensity, 4.10 [1.26] of 10; mean [SD] disability, 23.34 [10.12] of 100) and mean (SD) pain duration of 10.0 (8.9) years. Large group differences in pain were observed at posttreatment, with a mean (SD) pain score of 1.18 (1.24) in the PRT group, 2.84 (1.64) in the placebo group, and 3.13 (1.45) in the usual care group. Hedges g was -1.14 for PRT vs placebo and -1.74 for PRT vs usual care (P < .001). Of 151 total participants, 33 of 50 participants (66%) randomized to PRT were pain-free or nearly pain-free at posttreatment (reporting a pain intensity score of 0 or 1 of 10), compared with 10 of 51 participants (20%) randomized to placebo and 5 of 50 participants (10%) randomized to usual care. Treatment effects were maintained at 1-year follow-up, with a mean (SD) pain score of 1.51 (1.59) in the PRT group, 2.79 (1.78) in the placebo group, and 3.00 (1.77) in the usual care group. Hedges g was -0.70 for PRT vs placebo (P = .001) and -1.05 for PRT vs usual care (P < .001) at 1-year follow-up. Longitudinal fMRI showed (1) reduced responses to evoked back pain in the anterior midcingulate and the anterior prefrontal cortex for PRT vs placebo; (2) reduced responses in the anterior insula for PRT vs usual care; (3) increased resting connectivity from the anterior prefrontal cortex and the anterior insula to the primary somatosensory cortex for PRT vs both control groups; and (4) increased connectivity from the anterior midcingulate to the precuneus for PRT vs usual care.Conclusions and relevancePsychological treatment centered on changing patients' beliefs about the causes and threat value of pain may provide substantial and durable pain relief for people with CBP.Trial registrationClinicalTrials.gov Identifier: NCT03294148.
| S-EPMC8482298 | biostudies-literature
Project description:ImportanceCoronavirus disease 2019 (COVID-19) may lead to serious illness as a result of an excessive immune response. Fluvoxamine may prevent clinical deterioration by stimulating the σ-1 receptor, which regulates cytokine production.ObjectiveTo determine whether fluvoxamine, given during mild COVID-19 illness, prevents clinical deterioration and decreases the severity of disease.Design, setting, and participantsDouble-blind, randomized, fully remote (contactless) clinical trial of fluvoxamine vs placebo. Participants were community-living, nonhospitalized adults with confirmed severe acute respiratory syndrome coronavirus 2 infection, with COVID-19 symptom onset within 7 days and oxygen saturation of 92% or greater. One hundred fifty-two participants were enrolled from the St Louis metropolitan area (Missouri and Illinois) from April 10, 2020, to August 5, 2020. The final date of follow-up was September 19, 2020.InterventionsParticipants were randomly assigned to receive 100 mg of fluvoxamine (n = 80) or placebo (n = 72) 3 times daily for 15 days.Main outcomes and measuresThe primary outcome was clinical deterioration within 15 days of randomization defined by meeting both criteria of (1) shortness of breath or hospitalization for shortness of breath or pneumonia and (2) oxygen saturation less than 92% on room air or need for supplemental oxygen to achieve oxygen saturation of 92% or greater.ResultsOf 152 patients who were randomized (mean [SD] age, 46 [13] years; 109 [72%] women), 115 (76%) completed the trial. Clinical deterioration occurred in 0 of 80 patients in the fluvoxamine group and in 6 of 72 patients in the placebo group (absolute difference, 8.7% [95% CI, 1.8%-16.4%] from survival analysis; log-rank P = .009). The fluvoxamine group had 1 serious adverse event and 11 other adverse events, whereas the placebo group had 6 serious adverse events and 12 other adverse events.Conclusions and relevanceIn this preliminary study of adult outpatients with symptomatic COVID-19, patients treated with fluvoxamine, compared with placebo, had a lower likelihood of clinical deterioration over 15 days. However, the study is limited by a small sample size and short follow-up duration, and determination of clinical efficacy would require larger randomized trials with more definitive outcome measures.Trial registrationClinicalTrials.gov Identifier: NCT04342663.
| S-EPMC7662481 | biostudies-literature
Project description:ImportanceDiabetic foot ulcers are a common complication of diabetes and require specialized treatment. Cold atmospheric plasma (CAP) has been associated with benefits in wound infection and healing in previous smaller series of case reports. Yet the effect of CAP compared with standard care therapy in wound healing in diabetic foot ulcers remains to be studied.ObjectiveTo determine whether the application of CAP accelerates wound healing in diabetic foot ulcers compared with standard care therapy.Design, setting, and participantsA prospective, randomized, placebo-controlled, patient-blinded clinical trial was conducted at 2 clinics with recruitment from August 17, 2016, to April 20, 2019. Patients were scheduled to remain in follow-up until April 30, 2024. Patients with diabetes and diabetic foot ulcers described using the combined Wagner-Armstrong classification of 1B or 2B (superficial or infected diabetic foot ulcers extending to tendon) were eligible. A patient could participate with 1 or more wounds in both groups in both intervention and control groups. Wounds were randomized separately, allowing a participant to be treated several times within the study following a 2 × 2 × 2 randomization strata considering sex, smoking status, and age (≤68 years and >68 years).InterventionsStandard care treatment with 8 applications of either CAP generated from argon gas in an atmospheric pressure plasma jet or 8 applications of placebo treatment in a patient-blinded manner.Main outcomes and measuresPrimary end points were reduction in wound size, clinical infection, and microbial load compared with treatment start. Secondary end points were time to relevant wound reduction (>10%), reduction of infection, parameters of patient's well-being, and treatment-associated adverse events.ResultsOf 65 diabetic foot ulcer wounds from 45 patients assessed for study, 33 wounds from 29 patients were randomized to CAP and 32 wounds from 28 to placebo, with 62 wounds from 43 patients (31 wounds per group) included for final evaluation (mean [SD] age, 68.5 [9.1] years for full sample). Four patients with 5 wounds of 31 (16.1%) wounds in the CAP group and 3 patients with 4 wounds of 31 (13%) wounds in the placebo group were active smokers. CAP therapy yielded a significant increase in wound healing, both in total mean (SD) area reduction (CAP vs placebo relative units, -26.31 [11.72]; P = .03) and mean (SD) time to relevant wound area reduction (CAP vs placebo relative units, 10% from baseline, 1.60 [0.58]; P = .009). Reduction of infection and microbial load was not significantly different between CAP and placebo. No therapy-related adverse events occurred during therapy; patient's perceptions during therapy were comparable.Conclusions and relevanceIn this randomized clinical trial, CAP therapy resulted in beneficial effects in chronic wound treatment in terms of wound surface reduction and time to wound closure independent from background infection.Trial registrationClinicalTrials.gov Identifier: NCT04205942.
| S-EPMC7366186 | biostudies-literature